Rodent islet amyloid polypeptide (IAPP) selectively enhances GABA _A receptor-mediated neuronal inhibition in mouse ventral but not dorsal hippocampal dentate gyrus granule cells.

IF 4.2 3区医学 Q2 NEUROSCIENCES

Frontiers in Cellular Neuroscience Pub Date : 2025-02-19 eCollection Date: 2025-01-01 DOI:10.3389/fncel.2025.1531790

Olga Netsyk, Sergiy V Korol, Gunilla T Westermark, Bryndis Birnir, Zhe Jin

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Abstract

Islet amyloid polypeptide (IAPP, amylin) is a peptide hormone that plays an important role in glucose homeostasis but has been implicated in the pathophysiology of type 2 diabetes and Alzheimer's disease. However, its effect on neurotransmission in the hippocampus remains poorly understood. Here, we investigated the impact of non-amyloidogenic rodent IAPP (rIAPP) on GABA _A receptor-mediated neuronal inhibition in mouse dorsal and ventral hippocampal dentate gyrus (DG) granule cells. Using whole-cell patch-clamp recordings, we showed that rIAPP selectively enhanced both GABA-activated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in ventral, but not dorsal, hippocampal DG granule cells. The effect of rIAPP on sIPSCs was completely abolished in the presence of the amylin receptor antagonist IAPP_8-37. Interestingly, GABA _A receptor-mediated tonic current density remained unchanged in either dorsal or ventral hippocampal DG granule cells during rIAPP application. This region-specific and inhibition type-specific effect of rIAPP is likely associated with differential modulation of presynaptic GABA release as well as postsynaptic GABA _A receptors in the ventral as compared to the dorsal hippocampus. Our results suggest that rodent IAPP acts as a neuromodulator in hippocampal subregions by altering the strength of GABA _A receptor-mediated inhibitory signaling.

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啮齿动物胰岛淀粉样蛋白多肽（IAPP）选择性地增强GABA受体介导的小鼠海马齿状回颗粒细胞腹侧而非背侧的神经元抑制。

胰岛淀粉样多肽（IAPP, amylin）是一种肽激素，在葡萄糖稳态中起重要作用，但与2型糖尿病和阿尔茨海默病的病理生理有关。然而，它对海马体神经传递的影响仍然知之甚少。在这里，我们研究了非淀粉样变性啮齿类动物IAPP （rIAPP）对小鼠海马齿状回（DG）颗粒细胞背侧和腹侧GABA受体介导的神经元抑制的影响。通过全细胞膜片钳记录，我们发现rIAPP选择性地增强了gaba激活的海马DG颗粒细胞腹侧自发和微型抑制性突触后电流（sIPSCs和mIPSCs），而不是背侧。在胰淀素受体拮抗剂IAPP8-37的存在下，rIAPP对sIPSCs的作用被完全消除。有趣的是，在rIAPP应用期间，GABA A受体介导的海马DG颗粒细胞背侧和腹侧的紧张电流密度保持不变。与背侧海马相比，rIAPP的这种区域特异性和抑制类型特异性效应可能与突触前GABA释放和突触后GABA受体在腹侧的差异调节有关。我们的研究结果表明，啮齿动物IAPP通过改变GABA受体介导的抑制信号的强度，在海马亚区发挥神经调节剂的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cellular Neuroscience NEUROSCIENCES-

CiteScore

7.90

自引率

3.80%

发文量

627

审稿时长

6-12 weeks

期刊介绍： Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.