Early changes in exo-and endocytosis in the eae mouse model of multiple sclerosis correlate with decreased synaptic ribbon size and reduced ribbon-associated vesicle pools in rod photoreceptor synapses

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Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that finally leads to demyelination. Demyelinating optic neuritis is a frequent symptom in MS. Recent studies also revealed synapse dysfunctions in MS patients and MS mouse models. We previously reported alterations of photoreceptor ribbon synapses in the experimental auto-immune encephalomyelitis (EAE) mouse model of MS. In the present study, we found that the previously observed decreased imunosignals of photoreceptor ribbons in early EAE resulted from a decrease in synaptic ribbon size, whereas the number/density of ribbons in photoreceptor synapses remained un-changed. Smaller photoreceptor ribbons are associated with fewer docked and ribbon-associated vesicles. At a functional level, depolarization-evoked exocytosis as monitored by optical recording was diminished even as early as on day 7 after EAE induction. Moreover compensatory, post-de-polarization endocytosis was decreased. Decreased post-depolarization endocytosis in early EAE correlated with diminished synaptic enrichment of dynamin3. In contrast, basal endocytosis in photoreceptor synapses of resting non-depolarized retinal slices was increased in early EAE. Increased basal endocytosis correlated with increased de-phosphorylation of dynamin1. Thus, multiple endocytic pathways in photoreceptor synapse are differentially affected in early EAE and likely contribute to the observed synapse pathology in early EAE.

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Kesharwani, A., Schwarz, K., Dembla, E., Dembla, M., & Schmitz, F. (2021). Early changes in exo-and endocytosis in the eae mouse model of multiple sclerosis correlate with decreased synaptic ribbon size and reduced ribbon-associated vesicle pools in rod photoreceptor synapses. International Journal of Molecular Sciences, 22(19). https://doi.org/10.3390/ijms221910789

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