Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination

• Main Authors: Ilias Roufagalas, Maria Avloniti, Alexandra Fortosi, Evangelia Xingi, Dimitra Thomaidou, Lesley Probert, Vasiliki Kyrargyri
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Series: Neurobiology of Disease
• Subjects: MicroApp; Microglia heterogeneity; Brain surveillance; 2-photon imaging; Demyelination; Cuprizone
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996121001984

Microglia are key players in Multiple Sclerosis (MS), expressing many susceptibility genes for this disease. They constantly survey the brain microenvironment, but the precise functional relationships between microglia and pathological processes remain unknown. We performed a detailed assessment of microglial dynamics in three distinct grey matter regions in a cuprizone-induced demyelination model. We found that microglial activation preceded detectable demyelination and showed regional specificities, such as prominent phagocytic activity in cortical layer 5 and early hypertrophic morphology in hippocampal CA1. Demyelination happened earliest in cortical layer 5, although was more complete in CA1. In cortical layer 2/3, microglial activation and demyelination were less pronounced but microglia became hyper-ramified with slower process movement during remyelination, thereby maintaining local brain surveillance. Profiling of microglia using specific morphological and motility parameters revealed region-specific heterogeneity of microglial responses in the grey matter that might serve as sensitive indicators of progression in CNS demyelinating diseases.