Astroglial modulation of synaptic function in the non-demyelinated cerebellar cortex is dependent on MyD88 signaling in a model of toxic demyelination
Rattachement africain : de, at. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Progressive neurological decline in multiple sclerosis is associated with axonal loss and synaptic dysfunction in the non-demyelinated normal appearing gray matter (NAGM) and prominently in the cerebellum. In contrast to early disease stages, where synaptic and neuro-axonal pathology correlates with the extent of T cell infiltration, a prominent role of the innate immune system has been proposed for progressive MS. However, the specific contribution of microglia and astrocytes to synaptic cerebellar pathology in the NAGM- independent of an adaptive T cell response - remains largely unexplored. In the present study, we quantified synaptic changes in the cerebellar NAGM distant from demyelinated lesions in a mouse model of toxic demyelination. Proteomic analysis of the cerebellar cortex revealed differential regulation of synaptic and glutamate transport proteins in the absence of evident structural synaptic pathology or local gray matter demyelination. At the functional level, synaptic changes manifested as a reduction in frequency-dependent facilitation at the parallel fiber- Purkinje cell synapse. Further, deficiency of MyD88, an adaptor protein of the innate immune response, associated with a functional recovery in facilitation, reduced changes in the differential expression of synaptic and glutamate transport proteins, and reduced transcription levels of inflammatory cytokines. Nevertheless, the characteristics of demyelinating lesions and their associated cellular response were similar to wild type animals. Our work brings forward an experimental paradigm mimicking the diffuse synaptic pathology independent of demyelination in late stage MS and highlights the complex regulation of synaptic pathology in the cerebellar NAGM. Moreover, our findings suggest a role of astrocytes, in particular Bergmann glia, as key cellular determinants of cerebellar synaptic dysfunction.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Astroglial modulation of synaptic function in the non-demyelinated cerebellar cortex is dependent on MyD88 signaling in a model of toxic demyelination
- Date Crossref
- 23/02/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Universitätsmedizin Göttingen pays non établi dans la noticeÉtablissement de santé
-
Leipzig University pays non établi dans la noticeUniversité ou école supérieure
-
University of Vienna Department of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
-
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 pays non établi dans la noticeStructure de recherche
-
University of Göttingen Cluster of Excellence "Multiscale Bioimaging: From Molecular Machines to Network of Excitable Cells" (MBExC) pays non établi dans la noticeUniversité ou école supérieure
-
Campus Institute Data Science pays non établi dans la noticeStructure de recherche
-
University Medical Center Göttingen Department of Neuropathology pays non établi dans la noticeUniversité ou école supérieure
-
University of Leipzig Interdisciplinary Center for Bioinformatics (IZBI) pays non établi dans la noticeUniversité ou école supérieure
-
University Medical Center Leipzig Paul-Flechsig-Institute of Neuropathology pays non établi dans la noticeUniversité ou école supérieure
-
Max-Planck Institute for Multidisciplinary Sciences Department of Molecular Neurobiology pays non établi dans la noticeStructure de recherche
Universitätsmedizin Göttingen, Leipzig University et Department of Pharmaceutical Sciences — University of Vienna, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.