Histological and Functional Characterization of Connexin32 in A Model of Experimental Autoimmune Encephalitis

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease manifesting itself in de- and remyelination in the central nervous system (CNS) leading to consequent neuronal hyperexcitability and functionality damage. Recent studies found that loss of the gap-junction protein Cx32 is associated with occurrence of demyelinating disorders, downregulation of the GABAergic system and thereforehyperexcitability. Materials and Methods: Based on that we aimed to clarify the role of Cx32 in driving the pathophysiological process in MS. In order to achieve our goal, we initially performed immunohistochemistry to characterize the cytomorphology of the CNS of transgenicmice lacking Cx32 (KO). Results: Our results in- dicated that in Cx32-KO the content of myelin is 32% lower in comparison to control littermates (WT, n=3; p<0.0001). After inducing experimental autoimmune encephalitis (EAE) in mice by immunization with themyelin protein MOG35-55, Cx32-KO showed a significantly more severe phenotype in comparison to Cx32- WT approximately 15 days after immunization (4.9 ± 0.3 vs. 3.4 ± 0.2, respectively; n=10; p<0.001), when the disease is mainly characterized by neurodegeneration.Cx32-WT start recovering and remyelination while the Cx32-KO show a worsening of their clinical score. Conclusion: Taken together, our results suggest that a lack of Cx32 modifies the outcome of EAE by enhancing the effects of demyelination and impairing remyelinatingabilities, thereby leading to increased neuronal death and more severe symptoms