Ammonium chloride reduces excitatory synaptic transmission onto CA1 pyramidal neurons of mouse organotypic slice cultures.

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2024-10-01 eCollection Date: 2024-01-01 DOI:10.3389/fncel.2024.1410275
Dimitrios Kleidonas, Louis Hilfiger, Maximilian Lenz, Dieter Häussinger, Andreas Vlachos
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Abstract

Acute liver dysfunction commonly leads to rapid increases in ammonia concentrations in both the serum and the cerebrospinal fluid. These elevations primarily affect brain astrocytes, causing modifications in their structure and function. However, its impact on neurons is not yet fully understood. In this study, we investigated the impact of elevated ammonium chloride levels (NH4Cl, 5 mM) on synaptic transmission onto CA1 pyramidal neurons in mouse organotypic entorhino-hippocampal tissue cultures. We found that acute exposure to NH4Cl reversibly reduced excitatory synaptic transmission and affected CA3-CA1 synapses. Notably, NH4Cl modified astrocytic, but not CA1 pyramidal neuron, passive intrinsic properties. To further explore the role of astrocytes in NH4Cl-induced attenuation of synaptic transmission, we used methionine sulfoximine to target glutamine synthetase, a key astrocytic enzyme for ammonia clearance in the central nervous system. Inhibition of glutamine synthetase effectively prevented the downregulation of excitatory synaptic activity, underscoring the significant role of astrocytes in adjusting excitatory synapses during acute ammonia elevation.

氯化铵可减少小鼠器官型切片培养的 CA1 锥体神经元的兴奋性突触传递。
急性肝功能异常通常会导致血清和脑脊液中的氨浓度迅速升高。这些升高主要影响脑星形胶质细胞,导致其结构和功能发生改变。然而,氨对神经元的影响尚不完全清楚。在这项研究中,我们研究了氯化铵水平升高(NH4Cl,5 mM)对小鼠有机体内海马组织培养的 CA1 锥体神经元突触传递的影响。我们发现,急性暴露于 NH4Cl 会可逆地降低兴奋性突触传递并影响 CA3-CA1 突触。值得注意的是,NH4Cl 改变了星形胶质细胞而非 CA1 锥体神经元的被动内在特性。为了进一步探索星形胶质细胞在 NH4Cl 诱导的突触传递衰减中的作用,我们使用蛋氨酸亚砜亚胺靶向谷氨酰胺合成酶,这是中枢神经系统中清除氨的关键星形胶质细胞酶。抑制谷氨酰胺合成酶可有效防止兴奋性突触活动的下调,这突出表明了星形胶质细胞在急性氨升高时调整兴奋性突触的重要作用。
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
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.
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