Neonatal Exposure to Bacterial Lipopolysaccharide Affects Behavior and Expression of Ionotropic Glutamate Receptors in the Hippocampus of Adult Rats after Psychogenic Trauma

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Veronika A. Nikitina¹, Maria V. Zakharova², Alexander N. Trofimov¹, Alexander P. Schwarz², Gleb V. Beznin¹, Sergei G. Tsikunov¹, and Olga E. Zubareva^2,a*

¹Institute of Experimental Medicine, 197376 Saint Petersburg, Russia

²Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, Russia

^* To whom correspondence should be addressed.

Received December 6, 2020; Revised April 26, 2021; Accepted April 28, 2021

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According to the two-hit hypothesis of psychoneuropathology formation, infectious diseases and other pathological conditions occurring during the critical periods of early ontogenesis disrupt normal brain development and increase its susceptibility to stress experienced in adolescence and adulthood. It is believed that these disorders are associated with changes in the functional activity of the glutamatergic system in the hippocampus. Here, we studied expression of NMDA (GluN1, GluN2a, GluN2b) and AMPA (GluA1, GluA2) glutamate receptor subunits, as well as glutamate transporter EAAT2, in the ventral and dorsal regions of the hippocampus of rats injected with LPS during the third postnatal week and then subjected to predator stress (contact with a python) in adulthood. The tests were performed 25 days after the stress. It was found that stress altered protein expression in the ventral, but not in the dorsal hippocampus. Non-stressed LPS-treated rats displayed lower levels of the GluN2b protein in the ventral hippocampus vs. control animals. Stress significantly increased the content of GluN2b in the LPS-treated rats, but not in the control animals. Stress also affected differently the exploratory behavior of LPS-injected and control rats. Compared to the non-stressed animals, stressed control rats demonstrated a higher locomotor activity during the 1st min of the open field test, while the stressed LPS-injected rats displayed lower locomotor activity than the non-stressed rats. In addition, LPS-treated stressed and non-stressed rats spent more time in the open arms of the elevated plus maze and demonstrated reduced blood levels of corticosterone. To summarize the results of our study, exposure to bacterial LPS in the early postnatal ontogenesis affects the pattern of stress-induced changes in the behavior and hippocampal expression of genes coding for ionotropic glutamate receptor subunits after psychogenic trauma suffered in adulthood.

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KEY WORDS: lipopolysaccharide, early development, brain, stress reactivity, NMDA receptor, AMPA receptor, behavior

DOI: 10.1134/S0006297921060134

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