Expression of GABA-A Receptors and Cation-Chloride Cotransporters in the Hippocampus of Krushinsky–Molodkina Audiogenic Rats during the Postnatal Development

IF 0.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Evolutionary Biochemistry and Physiology Pub Date : 2024-06-26 DOI:10.1134/s0022093024030025

A. P. Ivlev, A. A. Naumova

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Abstract

Epilepsy development can be caused by impaired postsynaptic action of GABA that is mediated by altered expression of GABA-A receptors and cation-chloride cotransporters, KCC2 (K⁺/Cl^– cotransporter 2) and NKCC1 (Na⁺/K⁺/Cl^– cotransporter 1). In the present study, we analyzed the expression of GABA-A receptors, KCC2, and NKCC1 in the hippocampus of Krushinsky–Molodkina (KM) rats, genetically prone to audiogenic seizures (AGS), during the first few months of the postnatal development (at P15, P60, and P120). Wistar rats of the corresponding ages were used as the control groups. In the hippocampus of KM pups, we observed downregulation of both KCC2 and NKCC1; however, the expression of GABA-A receptor α1-subunit (GABAAR(α1)) was increased. Moreover, KCC2 was not detected in an abnormally broad region of the granular layer, indicating the Cl^– imbalance and impaired GABA-mediated inhibition in postsynaptic targets of GABA. These results suggested a delayed maturation of the hippocampal GABAergic system in KM rats in comparison with Wistar rats. In adult KM rats (P120) with fully developed susceptibility to AGS, normalization of both KCC2 and NKCC1 expression and KCC2 phosphorylation in the hippocampus was revealed. In contrast, GABAAR(α1) expression was decreased. We supposed that lower expression of GABA-A receptors in the hippocampus of adult KM rats might contribute either to the establishment of increased convulsive readiness or to hyperexcitation of the hippocampus during audiogenic kindling.

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克鲁申斯基-莫洛德金纳听觉致病大鼠海马中 GABA-A 受体和阳离子-氯离子共转运体在出生后发育过程中的表达

摘要癫痫的发生可能是由 GABA-A 受体和阳离子-氯化物共转运体 KCC2（K+/Cl- 共转运体 2）和 NKCC1（Na+/K+/Cl- 共转运体 1）的表达改变介导的 GABA 的突触后作用受损引起的。在本研究中，我们分析了遗传性易致听源性癫痫发作（AGS）的 Krushinsky-Molodkina (KM) 大鼠在出生后最初几个月（P15、P60 和 P120）的海马中 GABA-A 受体、KCC2 和 NKCC1 的表达情况。在 KM 幼鼠的海马中，我们观察到 KCC2 和 NKCC1 的下调，但 GABA-A 受体 α1-亚基（GABAAR(α1)）的表达增加。此外，在颗粒层正常宽阔的区域未检测到KCC2，这表明GABA突触后靶点的Cl-失衡和GABA介导的抑制作用受损。这些结果表明，与 Wistar 大鼠相比，KM 大鼠海马 GABA 能系统的成熟期推迟了。在对 AGS 有充分易感性的成年 KM 大鼠（P120）中，发现海马中 KCC2 和 NKCC1 的表达以及 KCC2 磷酸化均趋于正常。相反，GABAAR（α1）的表达却有所下降。我们认为，成年KM大鼠海马中GABA-A受体表达的降低可能是导致惊厥准备状态增强或致听性点燃时海马过度兴奋的原因之一。

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来源期刊

Journal of Evolutionary Biochemistry and Physiology 生物-进化生物学

自引率

33.30%

发文量

110

审稿时长

6-12 weeks

期刊介绍： Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.