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AMIGO3在幼鼠惊厥持续状态后异常神经回路形成中的作用及机制

The Role and Mechanism of AMIGO3 in the Formation of Aberrant Neural Circuits After Status Convulsion in Immature Mice.

作者信息

Li Xue, Pan Yanan, Gui Jianxiong, Fang Zhixu, Huang Dishu, Luo Hanyu, Cheng Li, Chen Hengsheng, Song Xiaojie, Jiang Li

机构信息

Chongqing Key Laboratory of Pediatrics, Department of Neurology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

出版信息

Front Mol Neurosci. 2021 Sep 28;14:748115. doi: 10.3389/fnmol.2021.748115. eCollection 2021.

DOI:10.3389/fnmol.2021.748115
PMID:34650403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8505997/
Abstract

Leucine rich repeat and immunoglobulin-like domain-containing protein 1 (Lingo-1) has gained considerable interest as a potential therapy for demyelinating diseases since it inhibits axonal regeneration and myelin production. However, the results of clinical trials targeted at Lingo-1 have been unsatisfactory. Amphoterin-induced gene and open reading frame-3 (AMIGO3), which is an analog of Lingo-1, might be an alternative therapeutic target for brain damage. In the present study, we investigated the effects of AMIGO3 on neural circuits in immature mice after status convulsion (SC) induced by kainic acid. The expression of both AMIGO3 and Lingo-1 was significantly increased after SC, with levels maintained to 20 days after SC. Following SC, transmission electron microscopy revealed the impaired microstructure of myelin sheaths and Western blot analysis showed a decrease in myelin basic protein expression, and this damage was alleviated by downregulation of AMIGO3 expression. The ROCK/RhoA signaling pathway was inhibited at 20 days after SC by downregulating AMIGO3 expression. These results indicate that AMIGO3 plays important roles in seizure-induced damage of myelin sheaths as well as axon growth and synaptic plasticity via the ROCK/RhoA signaling pathway.

摘要

富含亮氨酸重复序列和免疫球蛋白样结构域蛋白1（Lingo-1）因其抑制轴突再生和髓鞘生成，作为脱髓鞘疾病的潜在治疗方法而备受关注。然而，针对Lingo-1的临床试验结果并不理想。两性霉素诱导基因和开放阅读框-3（AMIGO3）是Lingo-1的类似物，可能是脑损伤的另一种治疗靶点。在本研究中，我们研究了AMIGO3对由海藻酸诱导的癫痫持续状态（SC）后未成熟小鼠神经回路的影响。SC后，AMIGO3和Lingo-1的表达均显著增加，并维持至SC后20天。SC后，透射电子显微镜显示髓鞘微结构受损，蛋白质免疫印迹分析显示髓鞘碱性蛋白表达降低，下调AMIGO3表达可减轻这种损伤。下调AMIGO3表达可在SC后20天抑制ROCK/RhoA信号通路。这些结果表明，AMIGO3在癫痫诱导的髓鞘损伤以及通过ROCK/RhoA信号通路的轴突生长和突触可塑性中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/1c1493fe988e/fnmol-14-748115-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/a90b9befef4a/fnmol-14-748115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/8be9b2bcc153/fnmol-14-748115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/9a2a73786046/fnmol-14-748115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/e0d770d69c02/fnmol-14-748115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/7e77a3c4f343/fnmol-14-748115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/af624a961efa/fnmol-14-748115-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/f94c8155f4c7/fnmol-14-748115-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/1c1493fe988e/fnmol-14-748115-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/a90b9befef4a/fnmol-14-748115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/8be9b2bcc153/fnmol-14-748115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/9a2a73786046/fnmol-14-748115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/e0d770d69c02/fnmol-14-748115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/7e77a3c4f343/fnmol-14-748115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/af624a961efa/fnmol-14-748115-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/f94c8155f4c7/fnmol-14-748115-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39e/8505997/1c1493fe988e/fnmol-14-748115-g008.jpg

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The relationship of seizure focus with depression, anxiety, and health-related quality of life in children and adolescents with epilepsy.癫痫患儿及青少年发作灶与抑郁、焦虑及健康相关生活质量的关系。
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