Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway

Journal of Neuroinflammation

Research

Vishwa Mohan¹  Puneet Opal²  Chandrakanth Reddy Edamakanti³ 

[1] Davee Department of Neurology, Northwestern University Feinberg School of Medicine, 60611, Chicago, IL, USA;Davee Department of Neurology, Northwestern University Feinberg School of Medicine, 60611, Chicago, IL, USA;Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, 60611, Chicago, IL, USA;Department of Neurology, Northwestern University Feinberg School of Medicine, Ward 10-332, 303 E. Chicago Ave, 60611, Chicago, IL, USA;Davee Department of Neurology, Northwestern University Feinberg School of Medicine, 60611, Chicago, IL, USA;Department of Neurology, Northwestern University Feinberg School of Medicine, Ward 10-332, 303 E. Chicago Ave, 60611, Chicago, IL, USA;Annexon Biosciences, 1400 Sierra Point Parkway Building C, 2nd Floor, 94005, Brisbane, CA, USA;

关键词: Spinocerebellar ataxia;    c-Jun;    Bergmann glia;    Neuroinflammation;    Cerebellum;    JNK signaling;   

DOI  :  10.1186/s12974-023-02801-1

 received in 2022-11-21, accepted in 2023-05-09,  发布年份 2023

来源: Springer

【 摘 要 】

The spinocerebellar ataxias (SCAs) are devastating neurological diseases characterized by progressive cerebellar incoordination. While neurons bear the brunt of the pathology, a growing body of evidence suggests that glial cells are also affected. It has, however, been difficult to understand the role of glia, given the diversity of subtypes, each with their individual contributions to neuronal health. Using human SCA autopsy samples we have discovered that Bergmann glia—the radial glia of the cerebellum, which form intimate functional connections with cerebellar Purkinje neurons—display inflammatory JNK-dependent c-Jun phosphorylation. This phosphorylation defines a signaling pathway not observed in other activated glial populations, providing an opportunity to isolate the role of Bergmann glia in SCA inflammation. Turning to an SCA1 mouse model as a paradigmatic SCA, we demonstrate that inhibiting the JNK pathway reduces Bergmann glia inflammation accompanied by improvements in the SCA1 phenotype both behaviorally and pathologically. These findings demonstrate the causal role for Bergmann glia inflammation in SCA1 and point to a novel therapeutic strategy that could span several ataxic syndromes where Bergmann glia inflammation is a major feature.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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