Влияние гомоцистеина и его производных на спонтанную сетевую активность в гиппокампе новорожденных крысят

Abstract

Homocysteine is a sulfur-containing amino acid, which at high concentrations induces neurotoxic effects and causes impairments in the development of the nervous system. In the blood homocysteine is rapidly oxidized, forming disulfide bonds with proteins and low-molecular thiols, and is also converted into homocysteine-thiolactone. Therefore during chronic exposure, homocysteine neurotoxicity is mediated by its derivatives. Our work aimed to study the effects of homocysteine, homocystine, and homocysteine-thiolactone on the network spontaneous activity of rat hippocampal neurons during the first postnatal week. Giant depolarizing potentials (GDP) and multiple-unit activities (MUA) were recorded using the extracellular electrode in the CA3 zone of the hippocampus. It was shown that all three thiol compounds induced an increase of the frequency of GDP and MUA in concentrations of 100 and 500 μM, while homocystine exerted the most profound effects on the network activity. Inhibition of NMDA and AMPA receptors completely prevented the effects of homocysteine and its derivatives on the spontaneous neuronal activity. Thus, homocysteine and its derivatives lead to the increase of network activity of hippocampal neurons of neonatal rats, which may impair the formation of hippocampal neuronal networks in chronic hyperhomocysteinemia; and may cause hyperexcitability and the risk of epilepsy development in the postnatal period.