摘要：SummaryMultiple sclerosis (MS) is a demyelinating disease caused by an auto-reactive immune system. Recent studies also demonstrated synapse dysfunctions in MS patients and MS mouse models. We previously observed decreased synaptic vesicle exocytosis in photoreceptor synapses in the EAE mouse model of MS at an early, preclinical stage. In the present study, we analyzed whether synaptic defects are associated with altered presynaptic Ca2+signaling. Using high-resolution immunolabeling, we found a reduced signal intensity of Cav-channels and RIM2 at active zones in early, preclinical EAE. In line with these morphological alterations, depolarization-evoked increases of presynaptic Ca2+were significantly smaller. In contrast, basal presynaptic Ca2+was elevated. We observed a decreased expression of Na+/K+-ATPase and plasma membrane Ca2+ATPase 2 (PMCA2), but not PMCA1, in photoreceptor terminals of EAE mice that could contribute to elevated basal Ca2+. Thus, complex Ca2+signaling alterations contribute to synaptic dysfunctions in photoreceptors in early EAE.Graphical AbstractDisplay OmittedHighlights•Less Cav-channels and RIM2 at the active zones of EAE photoreceptor synapses•Decreased depolarization-evoked Ca2+-responses in EAE photoreceptor synapses•Elevated basal, resting Ca2+levels in preclinical EAE photoreceptor terminals•Decreased expression of PMCA2 and Na+/K+-ATPase in EAE photoreceptor synapsesBiological Sciences; Molecular Biology; Neuroscience; Molecular Neuroscience; Cellular Neuroscience; Cell Biology
