Transmembrane protein modulates seizure in epilepsy: evidence from temporal lobe epilepsy patients and mouse models

Haiqing Zhang; Zunlin Zhou; Jiyao Qin; Juan Yang; Hao Huang; Xiaoyan Yang; Zhong Luo; Yongsu Zheng; Yan Peng; Ya Chen; Zucai Xu

doi:10.1538/expanim.23-0092

Original

Transmembrane protein modulates seizure in epilepsy: evidence from temporal lobe epilepsy patients and mouse models

Haiqing Zhang, Zunlin Zhou, Jiyao Qin, Juan Yang, Hao Huang, Xiaoyan Yang, Zhong Luo, Yongsu Zheng, Yan Peng, Ya Chen, Zucai Xu

Author information

Haiqing Zhang
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Zunlin Zhou
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Jiyao Qin
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Juan Yang
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Hao Huang
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Xiaoyan Yang
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Zhong Luo
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Yongsu Zheng
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Yan Peng
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Ya Chen
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China
Zucai Xu
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, P.R. China

Keywords: epilepsy, glutamate vesicular transporter 1 (VGLUT-1), seizure, transmembrane protein (TMEM230), vesicular γ-aminobutyric acid transporter (VGAT)

JOURNAL OPEN ACCESS

2024 Volume 73 Issue 2 Pages 162-174

DOI https://doi.org/10.1538/expanim.23-0092

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Abstract

Transmembrane protein (TMEM230) is located in secretory/recycling vesicles, including synaptic vesicles in neurons. However, the functional relationship between TMEM230 and epilepsy is still a mystery. The aims of this study were to investigate the expression of TMEM230 in patients with temporal lobe epilepsy (TLE) and two different mice models of chronic epilepsy, and to determine the probable roles of TMEM230 in epilepsy. Our results showed that TMEM230 expression was increased in the temporal neocortex of epileptic patients and the hippocampus and cortex of epileptic mice compared with that in the control tissues. Moreover, TMEM230 was mainly expressed in the neurons in both humans and mice epileptic brain. TMEM230 co-localized with glutamate vesicular transporter 1 (VGLUT-1), but not with vesicular γ-aminobutyric acid (GABA) transporter (VGAT). Mechanistically, coimmunoprecipitation confirmed that TMEM230 interacted with VGLUT-1, but not with VGAT in the hippocampus of epileptic mice. Lentivirus mediated overexpression of TMEM230 increased mice susceptibility to epilepsy and behavioural phenotypes of epileptic seizures during the kainite (KA)-induced chronic phase of epileptic seizures and the pentylenetetrazole (PTZ) kindling process, whereas lentivirus-mediated TMEM230 downregulation had the opposite effect. These results shed light on the functions of TMEM230 in neurons, suggesting that TMEM230 may play a critical role in the regulation of epileptic activity via influencing excitatory neurotransmission.

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