Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis

Progressive synaptic loss and dysfunction—also known as synaptopathy—occur early in multiple sclerosis (MS), and in experimental autoimmune encephalomyelitis (EAE), which is used to study MS in rodent modelsAlong with demyelination and axonal damage or transection, synaptopathy is a pathophysiological hallmark observed in MS and EAE; moreover, it is independent of axonal transection and demyelinationSynaptopathy has long-lasting effects that can be detrimental for motor and cognitive functionsIn MS and EAE, neuroinflammation alters the balance between the GABAergic and glutamatergic systems in the brain and spinal cordProinflammatory cytokines released during acute MS attacks increase glutamate-mediated synaptic transmission and reduce γ-aminobutyric acid-mediated synaptic signalling, resulting in unbalanced synaptic hyperexcitation and possibly also to neurodegenerationTargeting of mechanisms that stabilize, protect, repair or help regenerate synapses would enable clinical intervention at both early and late stages of the disease