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Updated: Oct 17, 2025
Bioluminescence and Near-infrared Imaging of Optic Neuritis and Brain Inflammation in the EAE Model of Multiple Sclerosis in Mice
Published on: March 1, 2017
Early Changes in Exo- and Endocytosis in the EAE Mouse Model of Multiple Sclerosis Correlate with Decreased Synaptic
Ajay Kesharwani1, Karin Schwarz1, Ekta Dembla1,2
1Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Medical School, Saarland University, 66421 Homburg, Germany.
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 unchanged. 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-depolarization 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.
Insights
Multiple sclerosis (MS) causes central nervous system inflammation and demyelination. In early MS, photoreceptor ribbon synapses shrink, impairing neurotransmitter release and altering vesicle cycling.
Area of Science:
- Neuroscience
- Ophthalmology
- Immunology
Background:
- Multiple sclerosis (MS) is a central nervous system inflammatory disease causing demyelination.
- Synapse dysfunction is increasingly recognized in MS.
- Photoreceptor ribbon synapse alterations were previously noted in the experimental autoimmune encephalomyelitis (EAE) mouse model.
Purpose of the Study:
- To investigate the specific changes in photoreceptor ribbon synapses during early stages of experimental autoimmune encephalomyelitis (EAE).
- To determine the functional consequences of these synaptic alterations on neurotransmitter release and recycling.
Main Methods:
- Utilized the EAE mouse model to study early-stage MS.
- Quantified synaptic ribbon size and density in photoreceptor synapses.
- Measured depolarization-evoked exocytosis and post-depolarization endocytosis using optical recording.
- Assessed the levels and phosphorylation status of key endocytic proteins like dynamin.
Main Results:
- Early EAE is characterized by decreased synaptic ribbon size, not density, in photoreceptors.
- Smaller ribbons correlated with fewer docked vesicles and reduced depolarization-evoked exocytosis.
- Post-depolarization endocytosis was diminished, linked to reduced dynamin3.
- Basal endocytosis increased, associated with elevated de-phosphorylated dynamin1.
Conclusions:
- Photoreceptor ribbon synapses exhibit significant structural and functional deficits in early EAE.
- Differential regulation of exocytosis and multiple endocytic pathways contributes to synapse pathology in early MS.
- These synaptic changes may underlie visual symptoms in multiple sclerosis.
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