miR-142-3p Is a Key Regulator of IL-1β-Dependent Synaptopathy in Neuroinflammation.
Georgia MandolesiFrancesca De VitoAlessandra MusellaAntonietta GentileSilvia BullittaDiego FresegnaHelena SepmanClaudio Di SanzaNabila HajiFrancesco MoriFabio ButtariEmerald PerlasMaria Teresa CiottiEran HornsteinIrene BozzoniCarlo PresuttiDiego CentonzePublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2017)
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.
Keyphrases
- multiple sclerosis
- white matter
- prognostic factors
- mass spectrometry
- oxidative stress
- mouse model
- ms ms
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- stem cells
- ejection fraction
- rheumatoid arthritis
- transcription factor
- cell therapy
- lipopolysaccharide induced
- resting state
- functional connectivity
- mesenchymal stem cells
- bone marrow
- peritoneal dialysis
- cerebrospinal fluid