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Updated: Jan 8, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Published on: November 6, 2017

LRRC8AはNMDA受容体活性の亢進とミトコンドリアアポトーシス経路の活性化により虚血性神経障害を媒介する

Chengli Qian^1,2, Linshu Huang¹, Ying Chen¹

¹Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Cell biology international

|December 22, 2025

Abstract:

Brain ischemia induces neuronal apoptosis, a key event in stroke pathology, but the underlying mechanisms remain incompletely understood. This study investigates the role of the volume-regulated anion channel subunit leucine-rich repeat-containing protein 8 A (LRRC8A) in ischemia-induced neuronal damage. In a rat model of middle cerebral artery occlusion (MCAO) and in cultured neurons under oxygen-glucose deprivation (OGD), ischemia/hypoxia rapidly upregulated LRRC8A expression in apoptotic neurons. Knockdown of lrrc8a via small interfering RNA (siRNA) attenuated brain infarction, improved neurological deficits, and reduced neuronal apoptosis. Mechanistically, lrrc8a knockdown suppressed the activation of the mitochondrial Bax/Bcl-2/Caspase-9/Caspase-3 apoptotic pathway. Furthermore, lrrc8a knockdown reversed OGD-induced hyperactivation of NMDA receptors (NMDARs) and weakened the enhanced interaction between LRRC8A and the obligatory NMDAR subunit GluN1, which was predicted by structural modeling. These findings reveal that cerebral ischemia upregulates neuronal LRRC8A, which may promote NMDAR hyperactivity via interaction with GluN1, thereby triggering mitochondrial apoptosis. LRRC8A represents a potential therapeutic target for mitigating neuronal apoptosis in ischemic stroke.

キーワード:

LRRC8A NMDA受容体 VRAC 脳虚血神経アポトーシス

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Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

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