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Semantic Scholar Open Access 2023 6 sitasi

GABAergic signaling abnormalities in a novel CLU mutation Alzheimer's disease mouse model.

Chunxia Chen Xihe Tang Zhaohui Lan Wan Chen Hua Su +8 lainnya
Lihat Sumber DOI

Abstrak

The CLU rs11136000C mutation (CLUC) is the third most common risk factor for Alzheimer's disease (AD). However, the mechanism by which CLUC leads to abnormal GABAergic signaling in AD is unclear. To address this question, this study establishes the first chimeric mouse model of CLUC AD. Examination of grafted CLUC medial ganglionic eminence progenitors (CLUC hiMGEs) revealed increased GAD65/67 and a high frequency of spontaneous releasing events. CLUC hiMGEs also impaired cognition in chimeric mice and caused AD-related pathologies. The expression of GABA A receptor, subunit alpha 2 (Gabrα2) was higher in chimeric mice. Interestingly, cognitive impairment in chimeric mice was reversed by treatment with pentylenetetrazole, which is a GABA A receptor inhibitor. Taken together, these findings shed light on the pathogenesis of CLUC AD using a novel humanized animal model and suggest sphingolipid signaling over-activation as a potential mechanism of GABAergic signaling disorder.

Topik & Kata Kunci

Medicine

Penulis (13)

C

Chunxia Chen

X

Xihe Tang

Z

Zhaohui Lan

W

Wan Chen

H

Hua Su

W

Weidong Li

Y

Yaoxuan Li

X

Xing Zhou

H

Hongyang Gao

X

Xinwei Feng

Y

Ying-Zi Guo

M

Meicun Yao

W

W. Deng

Format Sitasi

APA MLA BibTeX
Chen, C., Tang, X., Lan, Z., Chen, W., Su, H., Li, W. et al. (2023). GABAergic signaling abnormalities in a novel CLU mutation Alzheimer's disease mouse model.. https://doi.org/10.1016/j.trsl.2023.05.003

Akses Cepat

Lihat di Sumber doi.org/10.1016/j.trsl.2023.05.003
Informasi Jurnal
Tahun Terbit
2023
Bahasa
en
Total Sitasi
6×
Sumber Database
Semantic Scholar
DOI
10.1016/j.trsl.2023.05.003
Akses
Open Access ✓