Comparative Investigation of Expression of Glutamatergic and GABAergic Genes in the Rat Hippocampus after Focal Brain Ischemia and Central LPS Administration

---

Tatyana S. Kalinina¹, Galina T. Shishkina^1,a*, Dmitriy A. Lanshakov¹, Ekaterina V. Sukhareva¹, Mikhail V. Onufriev², Yulia V. Moiseeva², Natalia V. Gulyaeva², and Nikolay N. Dygalo¹

¹Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia

²Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences, 117485 Moscow, Russia

^* To whom correspondence should be addressed.

Received November 23, 2022; Revised March 14, 2023; Accepted March 14, 2023

---

Among the responses in the early stages of stroke, activation of neurodegenerative and proinflammatory processes in the hippocampus is of key importance for the development of negative post-ischemic functional consequences. However, it remains unclear, what genes are involved in these processes. The aim of this work was a comparative study of the expression of genes encoding glutamate and GABA transporters and receptors, as well as inflammation markers in the hippocampus one day after two types of middle cerebral artery occlusion (according to Koizumi et al. method, MCAO-MK, and Longa et al. method, MCAO-ML), and direct pro-inflammatory activation by central administration of bacterial lipopolysaccharide (LPS). Differences and similarities in the effects of these challenges on gene expression were observed. Expression of a larger number of genes associated with activation of apoptosis and neuroinflammation, glutamate reception, and markers of the GABAergic system changed after the MCAO-ML and LPS administration than after the MCAO-MK. Compared with the MCAO-ML, the MCAO-MK and LPS challenges caused changes in the expression of more genes involved in glutamate transport. The most pronounced difference between the responses to different challenges was the changes in expression of calmodulin and calmodulin-dependent kinases genes observed after MCAO, especially MCAO-ML, but not after LPS. The revealed specific features of the hippocampal gene responses to the two types of ischemia and a pro-inflammatory stimulus could contribute to further understanding of the molecular mechanisms underlying diversity of the post-stroke consequences both in the model studies and in the clinic.

---

KEY WORDS: hippocampus, middle cerebral artery occlusion, lipopolysaccharide, glutamate, GABA, gene expression

DOI: 10.1134/S0006297923040090

---