• Lixia Hao, Hui Zhang, Xiaoyan Peng, Yi Yang, Min Yang, Yi Guo, Xuefeng Wang, and Wei Jing.
• Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China; Department of Rehabilitation Medicine, the Affiliated Hospital of Inner Mongolia Medical University, China.
• Neuroscience. 2022 Nov 10; 504: 191-9.

AbstractEpilepsy is a neurological disorder caused by abnormally elevated neuronal firing and excitability. Spire2, also known as the nucleating factor of F-actin, plays an important role in long-range vesicle transport. This study showed that Spire2 was highly expressed in neurons in the cortex and hippocampus. Its knockdown significantly reduced the initiation current of the evoked action potential and the frequency of action potential, suggesting that Spire2 knockdown inhibits the threshold current of the neuron. In the cortex of patients with refractory temporal lobe epilepsy (TLE), Spire2 expression was significantly reduced. Decreased expression levels of Spire2 were also observed in kainic acid (KA) and pentylenetetrazole (PTZ) animal models. In the KA and PTZ models, Spire2-knockdown mice showed significantly increased seizures and shortened intervals between seizures, with a tendency to increase seizure duration. In contrast, Spire2-overexpressing mice showed reduced numbers of spontaneous seizures. In conclusion, this study revealed a significantly decreased expression of Spire2 in the brain tissues of epileptic individuals and an inhibitory role for this protein in the development of epilepsy. In addition, knockdown of Spire2 aggravated abnormal firing in epileptic mice, while its overexpression had the opposite effect. These findings provide new insights into the mechanism of epileptogenesis.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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