Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway
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 understa...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02801-1 |
| _version_ | 1797817849407864832 |
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| author | Chandrakanth Reddy Edamakanti Vishwa Mohan Puneet Opal |
| author_facet | Chandrakanth Reddy Edamakanti Vishwa Mohan Puneet Opal |
| author_sort | Chandrakanth Reddy Edamakanti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T08:59:30Z |
| format | Article |
| id | doaj.art-837e05f8b84846e2a7ea688eca43b956 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-03-13T08:59:30Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-837e05f8b84846e2a7ea688eca43b9562023-05-28T11:23:24ZengBMCJournal of Neuroinflammation1742-20942023-05-0120111310.1186/s12974-023-02801-1Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathwayChandrakanth Reddy Edamakanti0Vishwa Mohan1Puneet Opal2Davee Department of Neurology, Northwestern University Feinberg School of MedicineDavee Department of Neurology, Northwestern University Feinberg School of MedicineDavee Department of Neurology, Northwestern University Feinberg School of MedicineAbstract 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.https://doi.org/10.1186/s12974-023-02801-1Spinocerebellar ataxiac-JunBergmann gliaNeuroinflammationCerebellumJNK signaling |
| spellingShingle | Chandrakanth Reddy Edamakanti Vishwa Mohan Puneet Opal Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway Journal of Neuroinflammation Spinocerebellar ataxia c-Jun Bergmann glia Neuroinflammation Cerebellum JNK signaling |
| title | Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway |
| title_full | Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway |
| title_fullStr | Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway |
| title_full_unstemmed | Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway |
| title_short | Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway |
| title_sort | reactive bergmann glia play a central role in spinocerebellar ataxia inflammation via the jnk pathway |
| topic | Spinocerebellar ataxia c-Jun Bergmann glia Neuroinflammation Cerebellum JNK signaling |
| url | https://doi.org/10.1186/s12974-023-02801-1 |
| work_keys_str_mv | AT chandrakanthreddyedamakanti reactivebergmanngliaplayacentralroleinspinocerebellarataxiainflammationviathejnkpathway AT vishwamohan reactivebergmanngliaplayacentralroleinspinocerebellarataxiainflammationviathejnkpathway AT puneetopal reactivebergmanngliaplayacentralroleinspinocerebellarataxiainflammationviathejnkpathway |