Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway.
J Neuroinflammation
; 20(1): 126, 2023 May 26.
Article
en En
| MEDLINE
| ID: mdl-37237366
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ataxias Espinocerebelosas
/
Sistema de Señalización de MAP Quinasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Neuroinflammation
Asunto de la revista:
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos