MiR-142-3p Is a Key Regulator of IL-1β-Dependent Synaptopathy in Neuroinflammation

Overview

Journal J Neurosci

Specialty Neurology

Date 2017 Jan 20

PMID 28100738

Citations 63

Authors

Georgia Mandolesi

Francesca De Vito

Alessandra Musella

Antonietta Gentile

Silvia Bullitta

Diego Fresegna

Helena Sepman

Claudio Di Sanza

Nabila Haji

Francesco Mori

Fabio Buttari

Emerald Perlas

Maria Teresa Ciotti

Eran Hornstein

Irene Bozzoni

Carlo Presutti

Diego Centonze

Affiliations

Soon will be listed here.

Abstract

Significance Statement: Current studies suggest the role of glutamate excitotoxicity in the development and progression of multiple sclerosis (MS) and of its mouse model experimental autoimmune encephalomyelitis (EAE). The molecular mechanisms linking inflammation and synaptic alterations in MS/EAE are still unknown. Here, we identified miR-142-3p as a determinant molecular actor in inflammation-dependent synaptopathy typical of both MS and EAE. miR-142-3p was upregulated in the CSF of MS patients and in EAE cerebellum. Inhibition of miR-142-3p, locally in EAE brain and in a MS chimeric ex vivo model, recovered glutamatergic synaptic enhancement typical of EAE/MS. We proved that miR-142-3p promoted the IL-1β-dependent glutamate dysfunction by targeting glutamate-aspartate transporter (GLAST), a crucial glial transporter involved in glutamate homeostasis. Finally, we suggest miR-142-3p as a negative prognostic factor in patients with relapsing-remitting multiple sclerosis.

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