Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats.

Autor: Yakovlev AV; Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str 18, Kazan 420008, Russia. Electronic address: aleksey.yakovlev@kpfu.ru., Kurmashova E; Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str 18, Kazan 420008, Russia., Gataulina E; Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str 18, Kazan 420008, Russia., Gerasimova E; Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str 18, Kazan 420008, Russia., Khalilov I; Institut de Neurobiologie de la Méditerranée, INMED UMR901 Parc scientifique de Luminy, 163 avenue de Luminy BP13 - 13273, Marseille cedex 09, France; Laboratory of Neurobiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str 18, Kazan 420008, Russia., Sitdikova GF; Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str 18, Kazan 420008, Russia.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Sep 15; Vol. 329, pp. 121953. Date of Electronic Publication: 2023 Jul 17.
DOI: 10.1016/j.lfs.2023.121953
Abstrakt: Aims: Neonatal seizures are severe pathologies which may result in long-term neurological consequences. High plasma concentrations of homocysteine - hyperhomocysteinemia (hHCy) - are associated with epilepsy. In the present study, we evaluated susceptibility to seizure of neonatal rats with prenatal hHCy.
Main Methods: Prenatal hHCy was induced by feeding females with a high-methionine diet. Experiments were performed on pups during the first three postnatal weeks. Flurothyl-induced epileptic behavior was assessed according to Racine's scale. Epileptiform activity in the hippocampus was recorded using electrophysiological methods. The balance of excitation/inhibition, functional GABAergic inhibition and GABA reversal potential in hippocampal neurons were analyzed.
Key Findings: Rats with hHCy developed more severe stages of behavioral patterns during flurothyl-induced epilepsy with shorter latency. Electrophysiological recordings demonstrated higher background neuronal activity in rats with hHCy. Seizure-like events triggered by flurothyl (in vivo) or 4-aminopyridine (in vitro) showed shorter latency, higher power and amplitude. An increased glutamate/GABA synaptic ratio was shown in the pyramidal neurons of rats with hHCy and more slices demonstrated excitation by isoguvacine, a selective GABA(A) receptor agonist, during the first and second postnatal weeks. The GABA driving force and the reversal potential of GABA(A) currents were more positive during the second postnatal week for hHCy rats.
Significance: The higher susceptibility to seizures in rats with prenatal hHCy due to a shift in the balance of excitation/inhibition toward excitation may underlie the clinical evidence about the association of hHCy with an increased risk of epilepsy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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