The Influence of NADH-Cyb5-reductase inhibition on cholinergic system function and epileptiform activity in the hippocampus

Author: Sergo Gegechkori
Keywords: Hippocampus, epilepsy, reductase system, cholinergic system
Annotation:

Epilepsy is a chronic, progressive disease characterized by recurrent seizures. Frequent convulsive activity characteristic of it may cause structural changes in the highly epileptogenic structure of the brain, such as the hippocampus, caused by neuronal death. Both glutamatergic and cholinergic projections are found in the hippocampus. Acetylcholine is formed in connection with choline and acetyl-CoA. Acetylcholine exerts its functions in the CNS by activating nicotinic ionotropic and muscarinic G-protein-binding receptors. It has been observed that on the hippocampal pyramidal neurons, M1 receptors are colocalized with NMDA glutamatergic receptors. It has been shown that activation of this type of receptor by acetylcholine enhances NMDA responses. Due to the existing data on the mechanisms of epileptogenesis, hypercholinergic states can lead to excessive excitation of the pyramidal neurons in the hippocampus and cortex in general and cause the generation of epileptiform discharges. This study aimed to investigate the effect of reduced NADH-Cyb5 reductase activity on the cholinergic system in the early postnatal period and to study its effects on the development of the epileptiform activity. Depending on the purpose, the NADH-Cyb5 reductase system was inhibited using propylthiouracil, and its effects were evaluated accordingly (Rat NADH-Cytochrome b5 Reductase 3 (CYB5R3) ELISA Kit), ELISA Kit; And the biochemical method - (Choline / Acetylcholine Assay Kit (ab65345)) determined the levels of choline and acetylcholine, in particular, in the background of the statistically significant increase in choline levels, reduced amounts of acetylcholine. In parallel with immunological and biochemical studies, the experiment revealed a high emotional status of the animals in the context of impaired motor activity (open field test). Electrophysiological data showed reduced numbers and frequency of epileptic discharges after intrahippocampal application of kainic acid. in PTU-injected animals, with unchanged background neuronal activity in both the right and left hippocampus. This work was supported by “Shota Rustaveli National Science Foundation of Georgia (SRNSFG) [grant number MR-21-158]

Lecture files:

„NADH-Cyb5-რედუქტაზას ინჰიბირების გავლენა ქოლინერგული სისტემის ფუნქციონირებასა და ჰიპოკამპში ეპილეფტიფორმულ აქტივობაზე“ [ka]
„NADH-Cyb5-რედუქტაზას ინჰიბირების გავლენა ქოლინერგული სისტემის ფუნქციონირებასა და ჰიპოკამპში ეპილეფტიფორმულ აქტივობაზე“ [ka]