Pathohistological changes in the granular layer of the dentate gyrus in rats with chronic alcohol intoxication and the possibilities of their pharmacological correction with new derivatives of neuroactive amino acids

INTRODUCTION: Long-term alcohol consumption provokes damage to the central nervous system, in particular the dentate gyrus and hippocampus, leading to a decrease in cognitive functions. In this regard, the search for substances with a neuroprotective effect is relevant. It was previously shown that a derivative of glutamic acid (glufimet) and a derivative of gamma-aminobutyric acid (mefargin) limit anxiety and manifestations of obsessive-compulsive disorder in animals exposed to alcoholization.

AIM: Analysis of pathomorphological changes in the granular layer of the dentate gyrus in rats under conditions of chronic alcohol intoxication (CAI) and under the influence of glufimet and mefargin.

MATERIALS AND METHODS: The experiments were conducted on female Wistar rats divided into groups: 1 — intact rats; 2 — a control group of animals with CAI, which was modeled by replacing drinking water with 10% ethanol solution for 24 weeks; 3 and 4 — groups of rats, which, after the modeled CAI, were administered glufimet and mefargin respectively, once, intraperitoneally, for 14 days after the cessation of alcoholization; 5 — a group of alcoholized rats that received the comparison drug meldonium. Pathomorphological changes in the granular layer of the dentate gyrus were assessed, and morphometric parameters were calculated.

RESULTS: In the granular layer of the dentate gyrus of animals with CAI, areas of significant cellular depletion, a large number of sharply hyperchromic, shrunken neurons, cells with swelling phenomena, ectopic nucleoli and cytoplasmic hyperchromia, and widespread karyocytolysis were observed. Glufimet contributed to the preservation of the cytoarchitecture of the dentate gyrus. Microscopic examination revealed no hypocellular areas, the average area of perikarya and neuronal nuclei was larger than in animals with CAI by 19.6% and 14.2% respectively. The width of the granular layer of the dentate gyrus in rats treated with glufimet after CAI was virtually identical to that in intact group rats. The number of shrunken neurons with hyperchromatosis was 40% lower than in animals with CAI without treatment. Mefargin led to some improvement in the morphology of the dentate gyrus, but to a lesser extent compared to glufimet.

CONCLUSION: New derivatives of neuroactive amino acids helped to limit the negative impact of chronic alcohol intoxication on the cytoarchitecture of the dentate gyrus, with the neuroprotective effect more pronounced in glufimet, which may be the basis for developing a drug based on it to prevent the consequences of long-term alcohol consumption.