Article

ISSN 0006-2979, Biochemistry (Moscow), 2026, Vol. 91, No. 6, pp. 923-938 © Pleiades Publishing, Ltd., 2026.

923

Dose-Dependent Effects of Soy Lecithin Intake

on Synaptic Ultrastructure in Brain Neurons

and Behavioral Patterns of C57BL/6 Laboratory Mice

Lyubov A. Suldina

1,2#

, Ksenia N. Morozova

1,3#

, Konstantin S. Pavlov

Elena V. Kiseleva

, and Lidiya V. Boldyreva

1,a

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences,

630090 Novosibirsk, Russia

Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia

Novosibirsk State University, 630090 Novosibirsk, Russia

e-mail: boldyrevalv@neuronm.ru

Received January 16, 2026

Revised June 2, 2026

Accepted June 14, 2026

Abstract— Phospholipid preparations, including lecithin, are widely used as hepatoprotective and neuropro-

tective agents, while soy lecithin is intensively used in food industry, with its total dose in the modern human

diet potentially reaching high levels. Soy lecithin contains up to 70% of biologically active phospholipids: phos-

phatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid. These compounds

perform a spectrum of key cellular functions, including neuromediation processes, and ensure formation of

the cellular membrane structures and vesicles. Previously, in the mouse model of chronic intestinal inflam-

mation, behavioral changes were observed together with the significant increase in the relative content of

several phospholipid classes in the intestinal epithelial cells. The animals fed with soy lecithin, which con-

tains a mixture of these phospholipids, showed similar behavioral changes in the absence of inflammation:

impaired social recognition and behavior, reduced signs of compulsivity and anxiety, and increased aggres-

sion in males. In this study, we found that reducing the dose of soy lecithin in short-term administration

restores normal social recognition and behavior in the healthy C57BL/6 animals, while reduction in anxiety

is maintained. Comparative electron microscopy analysis of the neurons and synapses in the amygdala,

hypothalamus, and frontal motor cortex of the C57BL/6 animals treated with soy lecithin was conducted.

Dose-dependent and region-specific changes were observed. High-dose lecithin administration, both long-term

and short-term, reduced synapse density in the neuropil, and irregular synaptic vesicles were detected in

the amygdala and hypothalamus. Threefold reduction in the lecithin dosage resulted in the increase in the

number of vesicles per synapse in the hypothalamus and motor cortex. The obtained results demonstrate

dose-dependent effect of soy lecithin on the synaptic ultrastructure in the hypothalamus, amygdala, and motor

cortex of the frontal lobe, as well as on the behavioral patterns of the healthy C57BL/6 laboratory mice.

DOI: 10.1134/S0006297926600109

Keywords: phospholipids, soy lecithin, social behavior, anxiety, C57BL/6 mice, electron microscopy, ultrastruc-

tural analysis, synapse, synaptic vesicles, neuropil

* To whom correspondence should be addressed.

# These authors contributed equally to this study.

INTRODUCTION

Various classes of phospholipids (PLs) perform

key molecular and cellular functions in the nervous

system, and changes in their metabolism correlate

with the diseases and chronic inflammatory processes

[1-3]. The major phospholipids in the human brain are

phosphatidylcholine, phosphatidylethanolamine, and

phosphatidylserine, with their enrichment observed

in all cortical regions of the brain  [1]. The most com-

mon fatty acids in phosphatidylcholine are palmitic

SULDINA et al.924

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

and stearic acids at the sn-1 position, while in the

brain, phosphatidylcholine contains polyunsaturated

fatty acids at the sn-2 position, with docosahexaenoic

acid and arachidonic acid being the most common

in the human brain  [1,  2]. It has been suggested that

this structural composition of phosphatidylcholine

in the brain in combination with the properties of

cholesterol and other PLs ensures conformation and

fluidity necessary for functional activity of the neuro-

nal membranes. Phospholipids are not only the main

component of cell membranes and transport mole-

cules but also serve as substrates and precursors for

a wide spectrum of biologically active molecules that

regulate metabolic pathways in the gut–brain axis

[4,  5]. In the central nervous system (CNS), PLs are

closely linked to the processes critical for neurome-

diation mechanisms, such as adenosine triphosphate

(ATP) production, mitochondrial transport, and pro-

duction and secretion of neurotransmitters. For ex-

ample, it has been estimated that oxidation of PLs

provides, on average, 20% of the total energy produc-

tion in the brain  [6]. Phosphatidylcholine also serves

as a choline depot for the synthesis of the neurotrans-

mitter acetylcholine and, at the same time, acts as

a substrate for the synthesis of phosphatidic acid.

Sphingolipids, glycerophospholipids, and cholesterol

are involved not only in transmission of a spectrum

of cellular signals and formation of the lipid rafts,

maintaining energy and oxidative balance, but also

in axon myelination, blood-brain barrier formation,

and neuroinflammatory homeostasis regulation  [6-8].

Phospholipids play an important role in synapse for-

mation, neurotransmitter release, and signal trans-

mission, and phospholipid metabolism deregulation

is closely associated with various neurodegenerative

diseases. Enzymes and co-factors of phospholipid me-

tabolism are considered as therapeutic targets  [8,  9].

The membranes of synaptic vesicles consist of

phospholipids, with the largest proportions being

phosphatidylcholine, phosphatidylethanolamine, and

cholesterol. These phospholipids ensure physicochem-

ical properties of the neuronal membranes, which

are critical for neuromediation mechanisms  [10,  11].

Phosphatidylserine and phosphatidic acid act as key

signaling phospholipids in regulation of the synaptic

vesicle cycle  [11]. For example, phosphatidylserine in

the membrane of synaptic vesicles ensures interac-

tion with Rab and SNARE family proteins, providing

anchoring the synaptic vesicles at the presynaptic

membrane  [10-12]. Additionally, phosphatidylserine

mediates initiation of synaptic exocytosis by the Ca

sensor synaptotagmin-1, via its functional domains

(C2A and C2B) activation by phosphatidylserine only

in the presence of Ca

  [12]. Physicochemical proper-

ties of phosphatidic acid facilitate membrane bending

and instantaneous fusion upon neural impulse arrival.

Furthermore, phosphatidic acid acts as a critical co-

factor in stabilization of the synaptophysin complex,

as well as in positioning and activity of dynamin in

the mechanism of synaptic vesicles recycling  [6,  8].

Deficiency of both phosphatidic acid and phosphati-

dylinositol, which are precursors for PI(4,5)P

, leads

to deregulation of the synaptic vesicles docking on

the presynaptic membrane, inhibiting their recycling

cycle, and thus impairing the neuromediation  [6].

Connection between the regulation of the body’s

metabolic pathways and psychoemotional state has

become a highly relevant topic in the last decade.

A number of studies on the patients and animal

models indicate a much broader and more signifi-

cant influence than previously thought  [13,  14]. Mod-

ern scientific paradigm of the gut–brain axis has un-

dergone significant evolution: from a model focusing

exclusively on microbiome, the emphasis has shifted

to studying metabolic pathways that mediate modu-

lation of the CNS functions by active components en-

tering with food: through interaction with the enteric

nervous system; through changes in the composition

of the gut microbiota; and through various mecha-

nisms of delivery of active metabolites and their sub-

sequent effect on molecular and cellular processes in

the brain  [15, 16].

Previously, in the genetic model of chronic colitis

in mice with mutation in the Mucin-2 (Muc2) gene

it was shown that, on the one hand, there is a sig-

nificant change in the behavioral characteristics of

animals and, on the other hand, there is a change in

the metabolomic profile of intestinal and brain cells

[17,  18]. In Muc2 animals, social behavior disorders

were accompanied by the significant increase in the

levels of several forms of phospholipids in the intesti-

nal epithelial cells, most notably phosphatidylcholine,

phosphatidylserine, and phosphatidic acid  [17]. Since

metabolism of phospholipids is critically important

for the brain function, and phospholipids can cross

the intestinal and blood-brain barriers in various

forms of packaging, we have then performed studies

that revealed a significant effect of the dietary intake

of both a phospholipid mixture (phosphatidylcholine,

phosphatidylserine, and phosphatidic acid) and soy

lecithin (70% total content of a phospholipid mixture:

phosphatidylcholine, phosphatidylethanolamine, phos-

phatidylinositol, and phosphatidic acid) on the social

and sexual behavior of mice  [19,  20]. As a result, im-

pairments in social recognition and behavior, reduced

signs of compulsivity and anxiety, and increased ag-

gression in the males were observed with both long-

term and short-term intake of doses of soy lecithin by

the healthy animals, reproducing the findings of both

the same behavioral traits and the phospholipid en-

richment in the intestinal epithelium during chronic

inflammation in the Muc2 mice  [17,  18].

EFFECTS OF SOY LECITHIN ON SYNAPTIC STRUCTURE AND BEHAVIOR 925

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

This study is focused on the comparative analy-

sis of the effects of perinatal and short-term dietary

soy lecithin in high and reduced doses on the neu-

rons and synapses in the hypothalamus, amygdala,

and motor zone of the frontal cortex of the brain, as

well as on the behavioral patterns mediated by these

brain regions in the healthy C57BL/6 mice. The study

comprehensively investigates the effects of dietary

soy lecithin intake on neuromediation processes at

both the cellular level (ultrastructural analysis of syn-

apses) and the CNS level (behavioral phenotyping).

MATERIALS AND METHODS

Experimental animals. The study used C57BL/

6JNskrc (local subcolony of C57BL/6J, hereafter

C57BL/6) and BALB/cNskrc (local subcolony of BALB/c,

hereafter BALB/c) mouse strains. Animals were kept

in same-sex groups of 3-5 individuals in cages mea-

suring 37×21×15  cm (length×width×height) with

wood sawdust bedding in a conventional vivarium at

the Research Institute of Neurosciences and Medicine,

Novosibirsk. The 12D:12N (reversed) light regime was

maintained with temperature 20-22°C, free access to

standard full-ration dry granulated feed and puri-

fied water was provided to the laboratory rodents.

Exclusion criteria for animals from the experiment

included: weight loss of more than 20% of normal;

organic disorders of CNS functions, alopecia, infertil-

ity, abscesses, or injuries.

Diet. Experimental groups of C57BL/6 mice re-

ceived standard feed uniformly mixed with soy

lecithin (Solgar, USA; declared composition: 70%

phospholipid mixture: phosphatidylcholine, phospha-

tidylethanolamine, phosphatidylinositol, phosphatidic

acid) at a calculated daily dose per mouse, multi-

plied by the number of mice in the cage. Doses of

180  mg/mouse/day (high) and 60  mg/mouse/day (re-

duced) were chosen based on the previous metabolo-

mic data  [17,  18] and extrapolation of the potentially

achievable total levels of phospholipid consumption

within the modern human diet  [3]. The control

group received standard feed without additives. Feed

was placed in the feeder daily. Feed leftovers were

weighed daily for 2  weeks. Control of the daily intake

of the lecithin dose was carried out by calculating av-

erage amount of feed consumed per day per animal.

Perinatal feeding was carried out as follows:

pregnant C57BL/6 females (20  animals) from the sec-

ond week of pregnancy received feed with soy lec-

ithin at a dose of 180  mg/day per animal. The off-

spring continued to receive feed with the same dose

of substances until sample collection. For newborn

pups, lecithin intake occurred through the mother’s

milk, which continued to receive the lecithin diet.

Experimental groups were formed from adult

males of the same age (10-12  weeks), from the litters

of 20 females of the same age. At the age of 3  weeks,

males were separated into combined randomized

groups of 3-6 animals for subsequent perfusion and

sample preparation for transmission electron micros-

copy (TEM) (number of animals is indicated taking

into account subsequent exclusions during experi-

ments).

Short-term feeding: mature C57BL/6 males (age

10-12 weeks) received feed with soy lecithin at a dose

of 180 mg/day per animal for 2  weeks.

Short-term feeding with reduced dose: mature

C57BL/6 males (age 10-12  weeks) received feed with

soy lecithin at a dose of 60  mg/day per animal for

2  weeks.

Behavioral testing. The following experimental

groups of animals were formed:

1. Control group (n  =  10): sexually mature C57BL/6

males (age 10-12 weeks) receiving standard feed;

2. Reduced-dose lecithin group (n  =  10): sexually

mature C57BL/6 males (age 10-12 weeks) receiv-

ing soy lecithin at a dose of 60  mg/day per ani-

mal for 2  weeks.

Testing was conducted during the dark period

(for animals) under red lighting (unless otherwise

specified). Between tests, the arena of the setups was

cleaned with 70% ethanol solution to remove odors.

Open field test. A square plastic setup (40×40  cm)

with transparent walls and an opaque bottom was

used. Center of the field was defined as a 20×20  cm

square. Testing was conducted for 6  min. A mouse

was placed in the center of the field, and the fol-

lowing parameters were measured: distance traveled,

number of rearing, time spent in the center of the

field. All parameters were recorded and processed

using Ethovision XT10 software (Noldus Internation-

al Technology). Number of defecations and grooming

time were recorded visually.

Light–dark box test. A rectangular setup (42×

21×25  cm) consisting of two compartments separat-

ed by a partition with a 3×4  cm hole was used. The

dark compartment constitutes 1/3 of the setup. Test

was conducted with bright white lighting in the light

compartment and no lighting in the dark compart-

ment. A mouse was placed in the dark compartment,

facing away from the hole connecting the compart-

ments. Over 5  min, the following parameters were re-

corded using a camera positioned above: time of first

exit from the dark compartment, duration in the light

compartment, distance traveled in the light compart-

ment. All parameters were recorded and processed

using Ethovision XT10 software (Noldus International

Technology).

Marble burying test. The test was conducted

in clean plastic animal cages (37×21×15 cm). Wood

SULDINA et al.926

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

sawdust was poured onto the bottom of the cages

(4-cm depth), on which 20 glass marbles (diame-

ter  =  1.0  cm) were evenly distributed. Each mouse

was placed in the separate cage for 30  min. After-

ward, the mouse was removed from the cage, and

number of marbles covered with sawdust by more

than 70% was counted.

Social preference test (two-intruder test: male

and female). Four days before the test, males that

had received sexual experience using a previously

described method  [21] were placed in individual cag-

es. 10  BALB/c females and 10  BALB/c males  [22] were

used as intruders. One day before the test, sexually

mature female intruders were marked with a safe

dye in the scapular region. To perform the test, a fe-

male and male intruder were simultaneously placed

in the home cage with the test male, and the animals

were allowed to interact freely for 15  min. During

this time, a video recording was made, and duration

of chasing and sniffing (social contact), mounting

(sexual preference), and attacks (aggression) of the

test male toward the female and male intruders was

counted.

Social odor test. To assess olfactory preference, a

test male, which had previously received sexual expe-

rience  [21], was presented with soiled bedding sam-

ples from BALB/c females and males placed in two

mesh metal containers (diameter 6  cm) in the home

cage, since it is known that presence of sexual expe-

rience promotes manifestation of sexual motivation

in males  [23,  24]. A male explored the samples for

5  min, during which the time spent sniffing the soiled

bedding from females and males was counted. The

result was expressed as (time sniffing bedding from

female or male)/(total sniffing time) in percentages.

Transmission electron microscopy (TEM) ul-

trastructural analysis. For electron microscopy, an-

imals were kept and fed under the same conditions

as those used for behavioral phenotyping  [19,  20] to

exclude the influence of stress encountered during

testing on the ultrastructure of neurons. From each

animal in the comparison groups (control (n = 3 for

each experiment), perinatal lecithin intake (n = 3),

short-term lecithin intake (n  =  3), reduced-dose leci-

thin intake (n  =  3)), 3 brain regions (amygdala, hypo-

thalamus, frontal cortex) were obtained. The control

group of animals was formed from the animals of

the same age that were kept under the same condi-

tions (the only difference was the diet) as each of the

experimental groups. Prior to euthanasia mice were

anesthetized with Domitor intraperitoneal injection

of 75  μl per 10  g of mouse weight (Orion Pharma,

Espoo, Finland) and Zoletil intraperitoneal injection

of 60  μL per 10  g of mouse weight (Virbac Sante An-

imale, France). After 20  min intracardiac perfusion

was performed with 15  ml of physiological saline

followed by 15  ml 6% glutaraldehyde (AppliChem

GmbH, Germany) in physiological saline per animal.

For the experimental and control groups, perfusion of

animals and sample preparation were carried out si-

multaneously and under identical conditions. In total,

TEM analysis was performed for 6 paired comparison

groups (18  animals, 3 per group) in 54 brain region

samples (3  regions from each animal).

Before ultrastructural analysis of the obtained

samples, an analysis of the quality of perfusion, tis-

sue fixation, and preservation of intracellular mem-

brane and non-membrane structures was performed.

After perfusion with 6% glutaraldehyde in physi-

ological saline, brain regions were fixed in a 2.5%

glutaraldehyde solution in 0.1  M sodium cacodylate

buffer (pH  7.4) for 1  h at room temperature. Next,

they were washed three times with a 0.1  M  sodium

cacodylate buffer and post-fixed in a 1%  osmium

tetroxide solution with 0.8% potassium ferricyanide

for 1  h. Fixed samples were contrasted with a 1%  ura-

nyl acetate solution in water. Samples were dehy-

drated and embedded in an epoxy resin (Epon 812).

Semi-thin cross-sections (250  nm) were prepared,

stained with methylene blue, and preliminarily an-

alyzed using an Axioscope-4 microscope (Zeiss).

Ultra- thin sections (60  nm) for TEM were prepared

with a diamond knife using a Leica EM UC6 ultra-

microtome (Leica), and after that examined using a

JEM1400 transmission electron microscope (JEOL).

For each block, serial ultra-thin sections were pre-

pared, and at least 10 fields of view (neuropil) were

analyzed for the presence of synapses. TEM was per-

formed using equipment of the Shared Access Center

for Microscopic Analysis of Biological Objects of the

SB  RAS (FWNR-2026-0024).

Morphometric analysis. For morphometric

analysis, 3  animals per each of the 4 groups (control,

perinatal lecithin intake, short-term lecithin intake,

reduced-dose lecithin intake) were used – a total

of 12 animals. From each animal, 3 brain regions

(amygdala, hypothalamus, frontal cortex) were tak-

en. For each region, at least 10 fields of view were

analyzed. Relative density of synapses was calculat-

ed on electron micrographs of the neuropil at 8000×

magnification. For this, total area of the neuropil was

measured, then the number of synapses was counted

and related to the area of the neuropil as units/μm

Similarly, on micrographs of synapses at 25,000× mag-

nification, the synapse area was measured, the num-

ber of vesicles was counted, and related to the area

of the presynaptic terminal. Synaptic vesicles were

considered heterogeneous in case of significant de-

viation from a round shape and noticeable variation

in size parameters. Mitochondria were considered de-

fective if presence of pronounced matrix clarification,

fragmentation, or absence of cristae, or membrane

EFFECTS OF SOY LECITHIN ON SYNAPTIC STRUCTURE AND BEHAVIOR 927

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

integrity disorders were observed. The analysis was

performed in a blind manner.

Statistical analysis. Data are presented graph-

ically as a mean and standard error of the mean

(M  ±  SEM). Statistical analysis of the data was per-

formed using STATISTICA 12.0 (StatSoft TIBCO Soft-

ware) with the Student’s t-test for normally distrib-

uted data. Normality of the data distribution was

evaluated using the Shapiro–Wilk test. For comparing

samples with distribution different from normal, the

Mann–Whitney U  test was used. The significance level

was set at p  <  0.05.

RESULTS

To identify cellular effects of the soy lecithin in-

take on neuromediation processes that may underly

the previously identified behavioral pattern disorders

in animals [18-20], in this study, we performed com-

parative analysis of the ultrastructure of neurons and

synapses in the mice brain using transmission elec-

tron microscopy (TEM). Comparative ultrastructural

analysis of the samples from three brain regions was

conducted: amygdala and hypothalamus, which are

most involved in the regulation of social and sexual

behavior, anxiety, and aggression in mice  [25], as well

as motor zone of the frontal cortex for the following

groups of experimental animals:

1. Adult C57BL/6 males receiving soy lecithin long-

term perinatally;

2. Adult C57BL/6 males receiving soy lecithin short-

term (2  weeks);

3. Adult C57BL/6 males receiving a reduced dose of

soy lecithin short-term (2  weeks);

4. Control adult C57BL/6 males receiving standard

feed (n  =  3 per brain region and group, total

36  samples).

In all three studied brain regions of the exper-

imental groups, neurons exhibited typical ultrastruc-

tural morphology, with no deviations in the frequen-

cy of cell death (apoptosis and autophagy) traits,

such as nuclear and cellular fragmentation, plasma

membrane integrity disorders, vacuole formation,

and apoptotic bodies, observed in the brain samples

of animals from the lecithin-receiving groups and

control animals. Neurons in all three studied brain

regions exhibited morphological characteristics typi-

cal for each region.

Neurons of the amygdala (Fig.  1, a, d, g, j) have

a complex ultrastructure characteristic of highly ac-

tive neurons involved in emotion processing, memo-

ry, and decision-making. Neurons in this brain region

have a large nucleus, numerous mitochondria, rough

endoplasmic reticulum, and Golgi apparatus in the cy-

toplasm. This brain region is notable for its high syn-

apse density and axon myelination. Neurons of the

hypothalamus (Fig.  1, b, e, h, k) with characteristic

electron-light cytoplasm and a large nucleus showed

nuclear envelope invagination in all experimental

groups. The cytoplasm contained numerous mito-

chondria, rough endoplasmic reticulum, a developed

Golgi apparatus, and electron-dense neurosecretory

granules. Neurons of the motor zone of the frontal

cortex (Fig.  1, c, f, i, l) are relatively large, with large

light nucleus. The cytoplasm contains mitochondria,

endoplasmic reticulum cisternae, and free ribosomes,

and numerous synaptic contacts with other neurons

are observed. Representative electron micrographs in

Fig.  1 also show synaptic contacts with other neurons,

which are marked with a blue background. Thus, the

ultrastructural analysis of neurons from three brain

regions – amygdala, hypothalamus and motor zone

of the frontal cortex – did not reveal morphological

signs of neuronal death or other cellular disorders.

Next, we performed a detailed ultrastructural

analysis of synapses, since synaptic terminals are

directly involved in neuromediation processes.

Ultrastructural changes in the synapses could indicate

changes in mediatory processes in the studied brain

regions, which may underlie the observed behavioral

deviations in the animals receiving soy lecithin.

Effects of perinatal soy lecithin intake on

synaptic ultrastructure in the brain of C57BL/6

mice. TEM micrographs show representative imag-

es of the synaptic terminals from the studied brain

regions, containing synaptic vesicles, synaptic cleft,

and postsynaptic membrane (Fig.  2). For accurate as-

sessment of the extent of the synaptic ultrastructure

disruptions, morphometric and subsequent statistical

analysis was performed (Fig.  3). Active zone of the

synapse – the area of the presynaptic membrane

where vesicle fusion occurs for neurotransmitter re-

lease– is marked in Fig.  2 with white arrows. In this

zone, accumulations of synaptic vesicles containing

neurotransmitters are observed, with size of approx-

imately 20-25  nm, as well as mitochondria necessary

for supplying energy to the synaptic transmission

process. Opposite the active zone of the presynaptic

membrane, the postsynaptic density is visible, char-

acterized by the dense accumulation of protein mol-

ecules – receptors, ion channels, and signaling mole-

cules (marked in the images with black arrowheads).

Comparing ultrastructure of the synapses in the

animals that received lecithin perinatally, it should be

noted that in the neuropil of the amygdala and hy-

pothalamus, synaptic terminals are less frequent than

in the control (Fig.  2, Fig.  3). Moreover, synapses in

the brain samples of the perinatally lecithin-receiving

group are filled with the small vesicles of irregular

size and shape (Fig.  2, b  and  d), unlike the regular

vesicles in the control (Fig.  2, a  and  c). Number and

SULDINA et al.928

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  1. Representative electron micrographs of neurons in the studied brain regions: amygdala (a, d, g, j), hypothalamus  (b,  e,

h,  k), and motor zone of the frontal cortex (c, f, i, l) of healthy adult C57BL/6 males (a, b, c); adult C57BL/6 males long-term

perinatally receiving soy lecithin (d, e, f); adult C57BL/6 males short-term (2  weeks) receiving soy lecithin  (g,  h,  i); adult

C57BL/6 males receiving a reduced dose of soy lecithin (j, k, l). Designations: N – nucleus, mt – mitochondria, aG – Golgi

apparatus, gr – secretory granules, ms – myelin sheath, s – synapses.

EFFECTS OF SOY LECITHIN ON SYNAPTIC STRUCTURE AND BEHAVIOR 929

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  2. Representative electron micrographs of synaptic vesicles and the synaptic cleft of neurons in the amygdala  (a),

hypothalamus (c), and motor zone of the frontal cortex (e) in the brain of healthy adult C57BL/6 males, and in the amyg-

dala  (b), hypothalamus (d), and frontal cortex  (f) of the brains of adult C57BL/6 males long-term perinatally receiving soy

lecithin. Scale bar: 0.5  μm. White arrows indicate the active zone of the presynaptic membrane, black arrowheads indicate

postsynaptic density; asterisks indicate defective mitochondria, v – membrane vesicles, mt– mitochondria.

SULDINA et al.930

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig. 3. Morphometric TEM analysis of synaptic terminals in the neuropil and the number of synaptic vesicles in the studied

brain regions. a) Relative number of synaptic terminals per unit area of neuropil in sections in the amygdala, hypothal-

amus, and motor zone of the frontal cortex of control animals and animals treated with lecithin perinatally, short-term,

and short-term with a reduced dose. b)  Relative number of synaptic vesicles per unit area of synapse in neurons of the

amygdala, hypothalamus, and frontal cortex of adult C57BL/6 males treated with lecithin perinatally, short-term, and short-

term with a reduced dose of lecithin compared to control healthy adult C57BL/6 males. Comparison with the control group

was performed using the Mann–Whitney U-test. *  p  <  0.05, ***  p  <  0.001. n  =  3 animals per group.

density of synaptic vesicles in the synaptic terminals

of the hypothalamus are noticeably higher compared

to the control (Fig.  2, c  and  d, Fig.  3). In the synaptic

terminals of the experimental group, defective mi-

tochondria (marked with asterisks) and membrane

vesicles of irregular shape with electron-transparent

content are observed, which are not present in the

control (Fig.  2, c  and  d). Synapses in the hypothala-

mus of this group are characterized by formation of

the heterogeneous synaptic vesicles, unlike the regu-

lar vesicles of uniform shape and size in the control.

In the synapses of the motor zone of the frontal cor-

tex in the group that received lecithin perinatally, no

morphological disorders of synapses were detected

(Fig.  2, e  and  f), but significant decrease in the num-

ber of synaptic vesicles was recorded (Fig.  3).

Thus, according to the results of electron micros-

copy and morphometric analysis, relative number of

synapses per unit area of the neuropil in the mice

receiving lecithin perinatally is lower in the amyg-

dala and higher in the frontal cortex compared to

the control group (Fig.  3). At the same time, relative

number of the vesicles in synaptic terminals is low-

er in the amygdala and motor cortex and higher in

the hypothalamus in such animals compared to the

controls. Thus, decrease in the number of synapses

and density of vesicles in the neurons of the amygda-

la could indicate suppression of the neuromediation

functions in this brain region due to the long-term

perinatal intake of soy lecithin. At the same time, in

the motor cortex, decrease in the density of synaptic

vesicles may be compensated by the increase in the

relative number of synapses per unit area of neuropil

(Fig. 3).

Effects of short-term soy lecithin intake on

synaptic ultrastructure in the brain of C57BL/6

mice. According to the results of ultrastructural

analysis of the brain neurons in the animals receiv-

ing soy lecithin short-term (2  weeks), we have found

that even short-term lecithin intake causes changes

in the synaptic terminals of neurons and neuropil

(Fig.  4). In the synapses of neurons in the amygdala,

EFFECTS OF SOY LECITHIN ON SYNAPTIC STRUCTURE AND BEHAVIOR 931

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  4. Representative electron micrographs of synaptic vesicles and the synaptic cleft of neurons in the amygdala  (a),

hypothalamus (c), and motor zone of the frontal cortex (e) in the brain of healthy adult C57BL/6 males, and in the amyg-

dala  (b), hypothalamus (d), and frontal cortex  (f) of the brains of adult C57BL/6 males short-term (2  weeks) receiving soy

lecithin. Defective mitochondria are visible in the synaptic terminals of the amygdala and hypothalamus. Scale bar: 0.5  μm.

White arrows indicate the active zone of the presynaptic membrane; black arrowheads indicate the postsynaptic density;

asterisks indicate defective mitochondria.

SULDINA et al.932

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  5. Behavioral traits of control healthy adult C57BL/6 males and healthy adult C57BL/6 males short-term (2 weeks)

receiving the reduced dose of soy lecithin assessed in following behavioral tests: social odor test  (a); social preference

test (two-intruder test: male and female)  (b); open field test  (c); light–dark box test  (d); marble burying test  (e). per group.

Comparisons between the groups were performed using Student’s t-test (a, b, c, d) and the Mann–Whitney U  test  (e).

*  p  <  0.05, **  p  <  0.01, ***  p  <  0.001. n  =  10 animals per group.

decrease in the number of synaptic vesicles was ob-

served (Fig.  4b), which is in concordance with the

morphometric analysis data (Fig.  3). Also, relative

number of the synapses per unit area of neuropil

was lower compared to the control group (p  <  0.001)

(Fig.  3). In the hypothalamus of the animals receiving

lecithin short-term (2  weeks), synapse morphology is

close to normal, although defective mitochondria with

disrupted matrix without cristae were encountered

(Fig.  4d). Relative number of the synapses per unit

area of neuropil in the hypothalamus of the animals

receiving lecithin short-term compared to the control

group increased, although overall the number of syn-

apses per neuropil in the hypothalamus is lower than

in the amygdala (Fig.  3). Inthe frontal cortex, no sig-

nificant differences were observed (Fig.  4, e  and  f).

Synapses have typical appearance, clear synaptic

cleft, dense postsynaptic space, smooth synaptic ves-

icles, and normal mitochondria with smooth regular

cristae and dense matrix. No significant differences

were found between the number of synapses in the

neuropil of the frontal cortex after short-term lecithin

intake, nor in the number of synaptic vesicles per unit

area of the synapse, although the number of synaptic

vesicles per unit area of synapse increased (Fig.  3).

As with the long-term perinatal intake of high-dose

soy lecithin, relative number of the synapses per unit

area of neuropil in the mice after short-term lecithin

intake and relative number of synapses and synaptic

vesicles in the amygdala were lower, which may also

indicate impairment of synaptic transmission in this

brain region.

Reducing the dose of soy lecithin leads to the

decrease in the negative effects of high doses on so-

cial recognition and behavior in the C57BL/6 mice.

In the previous studies, we found that the healthy an-

imals receiving a phospholipid mixture or soy lecithin

with food demonstrated impairments in social recogni-

tion and behavior, reduced signs of compulsivity and

anxiety, and increased aggression in males  [19,  20].

EFFECTS OF SOY LECITHIN ON SYNAPTIC STRUCTURE AND BEHAVIOR 933

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  6. Representative electron micrographs of synaptic vesicles and the synaptic cleft of neurons in the amygdala  (a),

hypothalamus (c), and motor zone of the frontal cortex (e) in the brain of healthy adult C57BL/6 males, and in the amyg-

dala  (b), hypothalamus (d), and frontal cortex  (f) of the brains of adult C57BL/6 males short-term (2 weeks) receiving the

reduced dose of soy lecithin. Scale bar: 0.5 μm. White arrows indicate the active zone of the presynaptic membrane; black

arrowheads indicate postsynaptic density; mt – mitochondria.

SULDINA et al.934

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

To investigate social behavior of the animals receiv-

ing a reduced dose of lecithin, we conducted the so-

cial odor preference test and the two-intruder test

(male and female), which characterize sexual and

social preference in the animal behavior. The ani-

mals receiving a reduced dose of lecithin (60  mg/day

per animal) showed no differences from the control

group in social and sexual preference, demonstrating

natural high interest in females and reduced interest

in males, both in the two-intruder test and in the so-

cial odor recognition test (Fig.  5, a  and  b).

To assess the level of anxiety, motor, and explor-

atory activity of animals receiving a reduced dose

of lecithin compared to the control group, the Open

Field and Light–Dark Box tests were performed. The

animals receiving a reduced dose of lecithin traveled

a significantly greater distance in the light compart-

ment of the light–dark box (t  =  6.8517, p  <  0.001)

(Fig.  5c) than the control animals, indicating reduced

level of anxiety. At the same time, these animals

showed overall significantly higher motor activity in

the Open Field test (t  =  4.86318, p  =  0.008) (Fig.  5d).

These observations suggest reduction in anxiety and

increase in the motor and exploratory activity in the

animals receiving a reduced dose of lecithin. Next

the marble burying test was conducted to assess the

tendency of experimental animals to perform repet-

itive actions, characterizing obsessive behavior. The

group of animals receiving a reduced dose of lecithin

buried significantly fewer marbles compared to the

control group (U  =  16.5, p  =  0.04) (Fig.  5e).

Thus, as a result of reducing the dose of soy lec-

ithin in the diet of animals, we observed reversion

of the previously identified negative effects of high

doses of phospholipids on the stereotyped, social, and

sexual behavior  [19,  20], while the reduced anxiety

and obsessive behavior indicators persisted, along

with the increased motor and exploratory activity of

the animals, similar to the effects of high-dose phos-

pholipid and lecithin intake [19].

Effects of the reduced-dose soy lecithin in-

take on synaptic ultrastructure in the brain of

C57BL/6 mice. As a result of the comparative ultra-

structural analysis, a number of significant changes

were identified in the samples of amygdala, hypo-

thalamus, and motor zone of the frontal cortex of

the brain of the adult animals that received a re-

duced dose (60  mg/day per animal) of lecithin for a

short term, compared to the samples from the con-

trol group of animals (Fig.  6). In the neurons of the

amygdala, reduced relative number of the synapses

per unit area of neuropil was found compared to

the control group (p  <  0.001). Ultrastructural analy-

sis also showed that the two-week feeding with the

reduced dose of lecithin significantly increased rela-

tive number of the synaptic vesicles per unit area of

synapse in the neurons of the hypothalamus. At the

same time, in the neurons of the frontal cortex, rel-

ative number of the synaptic vesicles per unit area

of synapse decreased, as did the number of synaptic

vesicles per synapse (Fig.  3), which may indicate im-

pairment of synaptic transmission in this region. No-

tably, the similar decrease in the amygdala observed

with the perinatal and short-term intake of high-dose

soy lecithin in this experiment was manifested only

in the number of synapses, while no statistically

significant decrease in the number of vesicles was

observed.

DISCUSSION

The role of dietary derived metabolic triggers

in the psychoemotional state regulation and main-

taining in close connection with the influence of the

gut microbiome has been considered in the recent

decades within the paradigm of the gut–brain axis

[15,  16]. Despite the intensive growth of experimen-

tal data pool on metabolic pathways underlying the

gut–brain interaction and influence of the diet com-

ponents on CNS functions, this complex multifactorial

relationship remains largely unexplored  [26]. Metab-

olomic data obtained from the patients with chronic

inflammatory diseases and associated CNS disorders,

as well as from the patients with various psychoneu-

rological disorders, have revealed a significant role of

lipidome homeostasis and its dysregulation key role

in the pathological CNS states [5, 27, 28].

In the previous works, we showed that both

long-term and short-term intake of a phospholipid

mixture as well as soy lecithin by the healthy mice

at doses that could be relevant for the diet of modern

humans (taking into account food emulsifiers, dietary

supplements, and drugs) has a significant impact on

the behavioral traits – most notably on social recog-

nition and interaction, aggression levels in males, as

well as anxiety and obsessive-compulsive traits; addi-

tionally, perinatal intake also affected the schizophre-

nia-like traits, exploratory, and motor activity  [19,  20].

Doses of 180  mg/mouse/day (high) and 60  mg/mouse/

day (reduced) were selected based on the extrapola-

tion of potentially achievable levels of phospholipid

consumption in the diet of modern humans (taking

into account food emulsifiers, dietary supplements,

and drugs)  [17,  18]. For the newborn mice, the leci-

thin intake occurred through the mother’s milk, and

then grown-ups continued to receive the lecithin diet.

It was important for us to differentially assess both

the effects of perinatal exposure, simulating the pre-

viously identified shift in the phospholipid profile

during the course of chronic intestinal inflammation

in the pregnant mothers  [17], and then during the

EFFECTS OF SOY LECITHIN ON SYNAPTIC STRUCTURE AND BEHAVIOR 935

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

nursing of offspring, as well as effects of the direct

short-term consumption of lecithin by adult animals.

The obtained data agree with our previously pub-

lished results – dietary phospholipids intake repro-

duced a significant part of the behavioral features

that were observed in mice of the genetic model of

chronic intestinal inflammation  [17-20,  29]. Thus, we

established that the increase in the level of phos-

pholipids entering the gut with the diet causes the

same behavioral changes, which allows us to suggest

the role of metabolic effects of phospholipid intake

as part of soy lecithin on neuromediation processes

underlying the identified functional disorders of be-

havioral patterns  [19,  20].

Since in our previous studies  [20,  29], no signs of

inflammatory processes or disruption of the integrity

of the intestinal epithelial barrier were detected, we

assumed that the phospholipid intake may stimulate

production of the signaling metabolites in the intes-

tinal cells capable of crossing the blood-brain barri-

er, which next enter the brain with the bloodstream

and affect neuromediation processes. However, no

significant changes in the content of 57 such small

active metabolites in the blood and brain of mice re-

ceiving a mixture of exogenous phospholipids short-

term were detected by NMR  [20]. At the same time,

the ultrastructural changes identified in present work

(heterogeneity of synaptic vesicles, decreased synapse

density, mitochondrial defects in synaptic terminals)

indicate disruptions in neuromediation processes

(transport, uptake, vesicular cycle) in animals receiv-

ing soy lecithin.

Previously we have also identified significant

ultrastructural defects of mitochondria and dysreg-

ulation of mitochondrial functions in the entero-

cytes of animals receiving a phospholipid mixture

with diet [29]. We suggest that when high doses of

exogenous phospholipids are received with the diet

(in particular, as part of soy lecithin), phospholipids

could enter brain cells through the bloodstream in

the form of chylomicrons and exosomes, since phos-

pholipids in various forms are capable of penetrating

the blood-brain barrier  [30]. In this case, disruption

of the synaptic vesicle formation processes could oc-

cur due to significant deviations from the physiolog-

ical norms of stoichiometric ratios of phospholipids

in the neuronal membranes of the brain. For exam-

ple, it has been shown that lipid composition of the

membrane itself could affect perception of olfactory

signals, which could form the basis explaining the ob-

served disorders of social recognition in the animals

receiving high doses of soy lecithin  [31], which is con-

sistent with our previous data  [19,  20] and correlates

well with the fact of recovery of social behavior and

recognition observed in this work when the reduced

dose of soy lecithin was used (Fig.  4).

In addition, an important role could be played

by transformation of the dietary incoming phospho-

lipids into biologically active metabolites delivered

to the brain cells. For example, phosphatidylinositol

and phosphatidic acid, present in the soy lecithin, are

precursors for PI(4,5)P

, main regulator of the forma-

tion and docking of synaptic vesicles on the presyn-

aptic membrane; and disruption of its synthesis may

be the cause of observed neuromediation defects [6,

32]. Additionally, with the excess of phospholipids in

the cells, there may be disruption of their compart-

mentalization and membrane transport, which in the

neuromediation processes is manifested as deregu-

lation of the synaptic vesicle cycle and cessation of

the Ca

-dependent neurotransmitter release into the

synaptic cleft. This is consistent with the hypothesis

about the influence of the lipid composition of mem-

branes on the functioning of vesicular cycle proteins

and mitochondrial energy exchange. Previously, neg-

ative effect of the soy lecithin causing loss of mito-

chondrial membrane potential and mitochondrial

death has already been described  [31,  33].

With the long-term perinatal exposure to lec-

ithin, decrease in the relative number of synapses

per unit area of neuropil was observed in the amyg-

dala and hypothalamus, while small irregular vesi-

cles and defective mitochondria with the destroyed

matrix were detected in the synapses. The identified

changes could indicate disruptions in the synaptic

plasticity processes  [34,  35]. Unlike the amygdala and

hypothalamus, the motor zone of the frontal cortex,

which is responsible for motor functions of animals,

did not show such pronounced morphological devia-

tions with the long-term perinatal lecithin exposure.

Increase in the number of synaptic terminals in the

neuropil demonstrated by morphometric analysis

could be partially compensated by the decrease in

the density of synaptic vesicles in them but it still

indicates impairment of the synaptic transmission in

this brain region. In the study of behavioral patterns

of animals, we also previously observed increase in

the motor activity with both long-term and short-

term lecithin intake  [19,  20]. These effects persisted

even with the intake of a reduced dose studied in this

work.

The electron microscopy data obtained in this

study indicate neurotoxicity of lecithin, manifested

as mitochondrial damage and impairment of func-

tional synaptic transmission in the amygdala and

hypothalamus. Since both hypothalamus and amyg-

dala belong to the limbic system of the brain, we

could speak of the impairment of synaptic plasticity

of the limbic system, which is responsible for emo-

tions, motivation, social, and sexual behavior. Similar

to the negative effects observed with the high dos-

es, effects of the perinatal exposure to soy lecithin

SULDINA et al.936

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

on the catecholaminergic systems have previously

been observed, where the impulse activity of neu-

rons changed  [34]. Also, it has been shown that the

effect of soy lecithin preparations on the developing

rat pups affects macromolecular composition of the

immature brain cells and causes abnormal behavioral

patterns  [35]. At the same time, the short-term treat-

ment with the threefold reduced dose of lecithin did

not affect negatively the limbic system (disruption of

sexual and social interactions). However, the reduced

levels of anxiety and obsessive behavior persisted,

along with the increased exploratory activity, which,

under the used experimental conditions (in the ab-

sence of natural threats), could be considered as pos-

itive effects on the CNS of the short-term intake of

a moderate dose of phospholipids in composition of

lecithin. However, it should be mentioned that in the

natural environment, such change may have not only

adaptive but also maladaptive consequences depend-

ing on the context.

Lecithin is actively studied as a potential stimu-

lator of neurogenesis, but experimental data are am-

biguous. There are studies in which lecithin slowed

progression of mild cognitive impairments  [36]. Some

studies note protective effects of lecithin on the neu-

ronal networks in  vitro, and the lecithin-based nan-

oliposomes were shown to improve neuron develop-

ment  [35]. Our study demonstrates negative effects of

the long-term perinatal exposure to lecithin on the

neuromediation processes, leading to disorders of

behavioral patterns in mice. At the same time, the

reduced dose and short duration of intake has rather

positive effect on the psychoemotional indicators of

the laboratory C57BL/6 mice.

CONCLUSION

In this work, we identified dose-dependent and

region-specific effects of the dietary intake of exog-

enous phospholipids within the soy lecithin on the

healthy laboratory C57BL/6 mice. The effects were

specific to the amygdala and hypothalamus (limbic

system regions), as well as to the motor zone of the

frontal cortex. Further investigation of the molec-

ular and cellular mechanisms of the identified ef-

fects of soy lecithin intake on the regulation of CNS

functions could bring us closer to understanding the

role of the metabolic pathways of phospholipids and

their derivatives in the functioning of the gut–brain

axis. The results of our study also emphasize the

need for special caution in the long-term consump-

tion of high total doses of soy lecithin in food prod-

ucts and dietary supplements, especially in perinatal

diets.

Abbreviations

CNS central nervous system

PLs phospholipids

TEM transmission electron microscopy

Acknowledgments

The authors are grateful to S.  S.  Medvedeva for tech-

nical assistance in the samples collection and prepara-

tion for TEM, and to M.  V.  Morozova, E.  N.  Kozhevniko-

va, and T.  G.  Amstislavskaya for valuable advice in

planning experimental work and discussing the ob-

tained data. The authors express their gratitude to

the Shared Access Center for Microscopic Analysis of

Biological Objects of the IC&G SB RAS (FWNR-2026-

0024) for providing the equipment.

Contributions

L.  V.  Boldyreva, K.  N.  Morozova, and E.  V.  Kiseleva:

Concept and supervision of the work; L.  A.  Suldina,

L.  V.  Boldyreva, K.  N.  Morozova, and K.  S.  Pavlov:

Conducting experiments; processing and formatting

of the experimental data; L.  V.  Boldyreva, K.  N.  Mo-

rozova, and E.  V.  Kiseleva: Discussion of the research

results; L.  A.  Suldina, L.  V.  Boldyreva, and K.  N.  Moro-

zova: Writing text of the article.

Funding

This work was financially supported by the Russian

Science Foundation, project no. 23-25-00417 (https://

rscf.ru/project/23-25-00417/ [in Russian]). Assesment of

neurocognitive effects was carried out with the funds

from the federal budget for fundamental scientific re-

search of Federal State Budgetary Scientific Institution

“Scientific Research Institute of Neurosciences and

Medicine” (theme no. 126020316369-9).

Ethics approval and consent to participate

All applicable international, national, and/or insti-

tutional principles for the care and use of animals

were followed. All procedures performed in the ex-

periments involving animals were in accordance with

the ethical standards approved by the legal acts of the

Russian Federation, the principles of the Basel Dec-

laration, and the recommendations of the European

Convention for the Protection of Vertebrate Animals

Used for Experimental and Other Scientific Purposes

(ETS No. 123). All experimental procedures were ap-

proved by the Local Ethics Committee of the Scientif-

ic Research Institute of Neurosciences and Medicine

(Protocols no. 5 dated February 16, 2023, and no.  4

dated May 16, 2024).

Conflict of interest

The authors of this work declare that they have no

conflicts of interest.

EFFECTS OF SOY LECITHIN ON SYNAPTIC STRUCTURE AND BEHAVIOR 937

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

REFERENCES

1. Yoon, J. H., Seo, Y., Jo, Y. S., Lee, S., Cho, E., Cazenave-Gassiot, A., Shin, Y. S., Moon, M. H., An, H. J., Wenk, M. R.,

and Suh, P. G. (2022) Brain lipidomics: from functional landscape to clinical significance, Sci Adv., 16, eadc9317,

https://doi.org/10.1126/sciadv.adc9317.

2. Hornburg, D., Wu, S., Moqri, M., Zhou, X., Contrepois, K., Bararpour, N., Traber, G. M., Su, B., Metwally, A. A.,

Avina, M., Zhou, W., Ubellacker, J. M., Mishra, T., Schüssler-Fiorenza Rose, S. M., Kavathas, P. B., Williams, K. J.,

and Snyder, M. P. (2023) Dynamic lipidome alterations associated with human health, disease and ageing, Nat.

Metab., 5, 1578-1594, https://doi.org/10.1038/s42255-023-00880-1.

3. Boldyreva, L. V., Morozova, M. V., Saydakova, S. S., and Kozhevnikova, E. N. (2021) Fat of the gut: epithelial

phospholipids in inflammatory bowel diseases, Int. J. Mol. Sci., 22, 11682, https://doi.org/10.3390/ijms222111682.

4. Dias, C., and Nylandsted,J. (2021) Plasma membrane integrity in health and disease: significance and therapeutic

potential, Cell Discov., 7, 4, https://doi.org/10.1038/s41421-020-00233-2.

5. Boldyreva, L. V., Evtushenko, A.A., Lvova, M. N., Morozova, K. N., and Kiseleva, E. V. (2024) Underneath the gut–

brain axis in IBD – evidence of the non-obvious, Int. J. Mol. Sci., 25, e12125, https://doi.org/10.3390/ijms252212125.

6. Tracey, T. J., Steyn, F. J., Wolvetang, E. J., and Ngo, S. T. (2018) Neuronal lipid metabolism: multiple path-

ways driving functional outcomes in health and disease, Front. Mol. Neurosci., 11, 10, https://doi.org/10.3389/

fnmol.2018.00010.

7. Hussain, G., Wang, J., Rasul, A., Anwar, H., Imran, A., Qasim, M., Zafar, S., Kamran, S. K. S., Razzaq, A., Aziz, N.,

Ahmad, W., Shabbir, A., Iqbal, J., Baig, S. M., and Sun, T. (2019) Role of cholesterol and sphingolipids in brain

development and neurological diseases, Lipids Health Dis., 18, 26, https://doi.org/10.1186/s12944-019-0965-z.

8. Junpeng, L., Shasha, L., Yaning, Sh., Chanjuan, Zh., Li, Q., and Qidi, Ai. (2025) Targeting lipid metabolism in

neurodegenerative diseases: from experimental to clinical, Metabolism, 175, 156436, https://doi.org/10.1016/j.me-

tabol.2025.156436.

9. Tong, B., Ba, Y., Li, Z., Yang, C., Su, K., Qi, H., Zhang, D., Liu, X., Wu, Y., Chen, Y., Ling, J., Zhang, J., Yin, X., and

Yu, P. (2024) Targeting dysregulated lipid metabolism for the treatment of Alzheimer’s disease and Parkinson’s

disease: current advancements and future prospects, Neurobiol. Disease, 196, 106505, https://doi.org/10.1016/

j.nbd.2024.106505.

10. Binotti, B., Jahn, R., and Pérez-Lara, Á. (2021) An overview of the synaptic vesicle lipid composition, Arch.

Biochem. Biophys., 709, 108966, https://doi.org/10.1016/j.abb.2021.108966.

11. Takamori, S., Holt, M., Stenius, K., Lemke, E. A., Grønborg, M., Riedel, D., Urlaub, H., Schenck, S., Brügger, B.,

Ringler, P., Müller, S.A., Rammner, B., Gräter, F., Hub, J. S., De Groot, B.L., Mieskes,G., Moriyama,Y., Klingauf,J.,

Grubmüller, H., Heuser, J., Wieland, F., and Jahn, R. (2006) Molecular anatomy of a trafficking organelle, Cell,

17, 831-846, https://doi.org/10.1016/j.cell.2006.10.030.

12. Brunger, A. T., Leitz, J., Zhou, Q., Choi, U. B., and Lai, Y. (2018) Ca

-triggered synaptic vesicle fusion initiated

by release of inhibition, Trends Cell Biol., 28, 631-645, https://doi.org/10.1016/j.tcb.2018.03.004.

13. Humer, E., Probst, T., and Pieh, C. (2020) Metabolomics in psychiatric disorders: what we learn from animal

models, Metabolites, 1710, 72, https://doi.org/10.3390/metabo10020072.

14. Limon, V. M., Lee, M., Gonzalez, B., Choh, A. C., and Czerwinski, S. A. (2020) The impact of metabolic syn-

drome on mental health-related quality of life and depressive symptoms, Qual. Life Res., 29, 2063-2072, https://

doi.org/10.1007/s11136-020-02479-5.

15. Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., and Cryan, J. F.

(2021) Diet and the microbiota-gut-brain axis: sowing the seeds of good mental health, Adv. Nutr., 12, 1239-1285,

https://doi.org/10.1093/advances/nmaa181.

16. Yang, J., Kim, H. D., Barrila, J., Lee, S.-H., Nickerson, C. A., Ott, C. M., Israel, S. A., Choukér, A., and Yang, J.-Y.

(2025) Navigating mental health in space: gut–brain axis and microbiome dynamics, Exp. Mol. Med., 57, 1152-

1163, https://doi.org/10.1038/s12276-025-01488-z.

17. Borisova, M. A., Achasova, K. M., Morozova, K. N., Andreyeva, E. N., Litvinova, E. A., Ogienko, A. A.,

Morozova, M. V., Berkaeva, M. B., Kiseleva, E., and Kozhevnikova, E. N. (2020) Mucin-2 knockout is a model of

intercellular junction defects, mitochondrial damage and ATP depletion in the intestinal epithelium, Sci. Rep.,

10, e21135, https://doi.org/10.1038/s41598-020-78141-4.

18. Morozova, M. V., Borisova, M. A., Snytnikova, O. A., Achasova, K. M., Litvinova, E. A., Tsentalovich, Y. P., and

Kozhevnikova, E. N. (2022) Colitis-associated intestinal microbiota regulates brain glycine and host behavior in

mice, Sci. Rep., 12, e16345, https://doi.org/10.1038/s41598-022-19219-z.

19. Boldyreva, L. V., Morozova, M. V., Pavlov, K. S., and Kozhevnikova, E. N. (2024) Effect of dietary phospholipid

on the behavior in C57BL/6 mice, J. Evol. Biochem. Phys., 60, 409-419, https://doi.org/10.1134/S0022093024010319.

SULDINA et al.938

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

20. Morozova, M., Andrejeva, J., Snytnikova, O., Boldyreva, L., and Tsentalovich, Y. (2024) Phospholipid supplemen-

tation inhibits male and female odor discrimination in mice, Front. Behav. Neurosci., 18, e1397284, https://

doi.org/10.3389/fnbeh.2024.1397284.

21. Morozova, M. V., Boldyreva, L. V., Borisova, M. A., and Kozhevnikova, E. N. (2024) Investigating social com-

munication in mice: a two-intruders test approach, J.Neurosci. Res., 102, e25365, https://doi.org/10.1002/

jnr.25365.

22. Novikov, S. N. (1988) Pheromones and reproduction in mammals, Nauka, Moscow.

23. Amstislavskaya, T. G., Bulygina, V. V., Tikhonova, M.A., and Maslova, L. N. (2013) Social isolation during peri-ad-

olescence or adulthood: effects on sexual motivation, testosterone and corticosterone response under conditions

of sexual arousal in male rats, Chin. J. Physiol., 56, 36-43, https://doi.org/10.4077/CJP.2013.BAA074.

24. Zolotykh, M. A., and Kozhevnikova, E. N. (2017) The effect of social experience on olfactory preference in male

mice, Appl. Anim. Behav. Sci., 189, 85-90, https://doi.org/10.1016/j.applanim.2017.01.013.

25. Yamaguchi, T. (2022) Neural circuit mechanisms of sex and fighting in male mice, Neurosci. Res., 174, 1-8,

https://doi.org/10.1016/j.neures.2021.06.005.

26. Ajay, A., Singh Gaur, S., Singh, J., Shams, R., Dash, K., Mukarram, A., and Kovács, B. (2026) Dietary influences

on the gut-brain pathways: mechanisms and therapeutic potential, Hum. Nutr. Metab., 43, e200349, https://

doi.org/10.1016/j.hnm.2025.200349.

27. Lassale, C., Batty, G.D., Baghdadli,A., Jacka,F., Sánchez-Villegas, A., Kivimäki,M., and Akbaraly,T. (2019) Healthy

dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies,

Mol. Psychiatry, 24, 965-986, https://doi.org/10.1038/s41380-018-0237-8.

28. Ge, Z., Hu, Y., Kan, W., Li, L., Xu, J., Zhang, Y., Zheng, N., Wang, G., and Du, J. (2025) Lipid metabolic dysreg-

ulation-induced neuroinflammation in the pathophysiology of major depressive disorder, Front. Immunol, 16,

e1625087, https://doi.org/10.3389/fimmu.2025.1625087.

29. Saydakova, S., Morozova, K., Snytnikova, O., Morozova, M., Boldyreva, L., Kiseleva, E., Tsentalovich, Y., and

Kozhevnikova, E. (2023) The effect of dietary phospholipids on the ultrastructure and function of intestinal

epithelial cells, Int. J. Mol. Sci., 24, 1788, https://doi.org/10.3390/ijms24021788.

30. Pifferi, F., Laurent, B., and Plourde, M. (2021) Lipid transport and metabolism at the blood-brain interface:

implications in health and disease, Front. Physiol., 12, 645646, https://doi.org/10.3389/fphys.2021.645646.

31. Lowry, T. W., Kusi-Appiah, A. E., Fadool, D. A., and Lenher, T. S. (2023) Odor discrimination by lipid membranes,

Membranes (Basel), 13, 151, https://doi.org/10.3390/membranes13020151.

32. Guo,J., Wenk, M. R., Pellegrini, L., Onofri, F., Benfenati,F., and De Camilli, P. (2003) Phosphatidylinositol 4-kinase

type IIalpha is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles, Proc.

Natl. Acad. Sci. USA, 100, 3995-4000, https://doi.org/10.1073/pnas.0230488100.

33. Del Valle, I., Gómez-Durán, A., Holt, W. V., Muiño-Blanco, T., and Cebrián-Pérez, J. A. (2012) Soy lecithin inter-

feres with mitochondrial function in frozen-thawed ram spermatozoa, J. Androl., 33, 717-725, https://doi.org/

10.2164/jandrol.111.014944.

34. Bell, J. M., Whitmore, W. L., Cowdery, T., and Slotkin, T. A. (1986) Perinatal dietary supplementation with a soy

lecithin preparation: effects on development of central catecholaminergic neurotransmitter systems, Brain Res.

Bull., 17, 189-195, https://doi.org/10.1016/0361-9230(86)90115-2.

35. Wang, X., Li, D., Li, X. Y., Lu, W., Ding, H., Qi, C., Wang,X., Shen, J., Chi, Y., Li,T., Dunk, M. M., An, Y., Huang, H.,

Yu, K., Xu, W., Xiao, R., and Xi, Y. (2025) Lecithin alleviates memory deficits and muscle attenuation in Chinese

older adults and SAMP8 mice, Adv. Sci. (Weinh), 12, e2405222, https://doi.org/10.1002/advs.202405222.

36. Latifi, S., Tamayol, A., Habibey, R., Sabzevari, R., Kahn, C., Geny, D., Eftekharpour, E., Annabi, N., Blau, A.,

Linder, M., and Arab-Tehrany, E. (2016) Natural lecithin promotes neural network complexity and activity, Sci

Rep, 6, 25777, https://doi.org/10.1038/srep25777.

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published

maps and institutional affiliations. AI tools may have been used in the translation or editing of this article.