Alternative splicing of neurexins 1-3 is modulated by neuroinflammation in the prefrontal cortex of a murine model of multiple sclerosis.

Alternative splicing of neurexins 1-3 is modulated by neuroinflammation in the prefrontal cortex of a murine model of multiple sclerosis. Exp Neurol. 2020 Oct 12;:113497 Authors: Marchese E, Valentini M, Sante GD, Cesari E, Adinolfi A, Corvino V, Ria F, Sette C, Geloso MC Abstract Mounting evidence points to immune-mediated synaptopathy and impaired plasticity as early pathogenic events underlying cognitive decline (CD) in Multiple sclerosis (MS) and in the experimental autoimmune encephalopathy (EAE) mouse model of the disease. However, knowledge of the neurobiology of synaptic dysfunction is still incomplete. Splicing regulation represents a flexible and powerful mechanism involved in dynamic remodeling of the synapse, which allows the expression of synaptic protein variants that dynamically control the specificity of contacts between neurons. The pre-synaptic adhesion molecules neurexins (NRXNs) 1-3 play a relevant role in cognition and are alternatively spliced to yield variants that differentially cluster specific ligands in the postsynaptic compartment and modulate functional properties of the synaptic contact. Notably, mutations in these genes or disruption of their splicing program are associated with neuropsychiatric disorders. Herein, we have investigated how inflammatory changes imposed by EAE impact on alternative splicing of the Nrxn 1-3 mouse genes in the acute phase of disease. Due to its relevance in cognition, we foc...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research