Нейрохимические особенности организации нижних бугров четверохолмия крыс линии Крушинского–Молодкиной при формировании судорожной готовности

Abstract

To reveal abnormalities in the inferior colliculus during postnatal development of seizure susceptibility in audiogenic rats, an analysis of neurochemical markers, which characterized a functional state of glutamate and GABA neurons, was done. Krushinsky-Molodkina rats (KM) were used in the experiments. These rats demonstrate age-dependent development of audiogenic seizures (AGS), which expression is regulated by brain stem structures such as inferior colliculus. In the critical period of the development of AGS susceptibility (P14, P30, and P60) in KM rats, the activity of ERK1/2 kinase was significantly increased. Also, we observed upregulation of ERK-dependent proteins GluN2B and VGLUT2 that can mediate pathological alterations in the glutamate neurotransmission and subsequently initiate the development of epileptiform activity. In adult KM rats, the activity of ERK1/2 and expression of GluN2B and VGLUT2 was decreased. Also, our data showed enhanced expression of parvalbumin and GAD67, which are the markers of the GABAergic system, during the development of seizure susceptibility. While in adult KM rats expression levels of parvalbumin and GAD67 were significantly lower in comparison with Wistar rats that is one of the possible mechanisms for the completion of the formation of seizure susceptibility and the development of stable expression of AGS. Thus, we demonstrated neurochemical aberrations in the inferior colliculus during the development of neuronal interactions in postnatal ontogenesis that can cause delayed alterations leading to expression of epileptiform activity.