Audiogenic kindling activates glutamatergic system in the hippocampus of rats with genetic predisposition to audiogenic seizures.

Autor: Aleksandrova EP; Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, St. Petersburg, Russia., Ivlev AP; Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, St. Petersburg, Russia., Kulikov AA; Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, St. Petersburg, Russia., Naumova AA; Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, St. Petersburg, Russia., Glazova MV; Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, St. Petersburg, Russia. Electronic address: mglazova@iephb.ru., Chernigovskaya EV; Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2024 Apr 15; Vol. 1829, pp. 148792. Date of Electronic Publication: 2024 Feb 05.
DOI: 10.1016/j.brainres.2024.148792
Abstrakt: Temporal lobe epilepsy (TLE) development is associated with dysregulation of glutamatergic transmission in the hippocampus; however, detailed molecular mechanisms of pathological changes are still poorly understood. In the present study, we performed the complex analysis of glutamatergic system in the hippocampus of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). Daily AGS stimulations (audiogenic kindling) were used to reproduce the dynamics of TLE development. Naïve KM rats were used as a control. After 14 AGS, at the stage of developing TLE, KM rats demonstrated significant upregulation of extracellular signal-regulated kinases (ERK) 1 and 2, cAMP response element-binding protein (CREB), and c-Fos in the hippocampus indicating activation of the hippocampal cells. These changes were accompanied with an increase in glutaminase and vesicular glutamate transporter (VGLUT) 2 suggesting the activation of glutamate production and loading into the synaptic vesicles. After 21 AGS, when TLE was fully-established, alterations were similar but more pronounced, with higher activation of glutaminase, increase in glutamate production, upregulation of VGLUT1 and 2, and Fos-related antigen 1 (Fra-1) along with c-Fos. Analysis of glutamate receptors showed variable changes. Thus, after 14 AGS, simultaneous increase in metabotropic glutamate receptor mGluR1 and decrease in ionotropic N-methyl-D-aspartate (NMDA) receptors could reflect compensatory anti-epileptic mechanism, while further kindling progression induced upregulation of ionotropic receptors, probably, contributing to the hippocampal epileptization. However, we revealed practically no alterations in the expression of synaptic proteins. Altogether, obtained results suggested that overactivation of glutamate production in the hippocampus strongly contributed to TLE development in KM rats.
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 © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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