Disorders of the Nervous System
Author: Federico Ezequiel Occhiuzzi | Email: fede.occh@gmail.com
Vanesa Soledad Mattera1°, Federico Ezequiel Occhiuzzi1°, Maria Silvina Marcora1°, Juana Maria Pasquini1°, Jorge Daniel Correale2°, Laura Andrea Pasquini1°
1° IQUIFIB Department of Biological Chemistry – University of Buenos Aires
2° Institute for Neurological Research Dr. Raúl Carrea. FLENI
Multiple Sclerosis (MS) is a chronic demyelinating disease that acts on mature oligodendrocytes (OLm), characterized by reactive gliosis, inflammation and demyelination (Dem). Current therapies are focused on reducing inflammation, but little is known about drugs that stimulate remyelination (Rem). Rem is an example of spontaneous repair in the adult central nervous system, where new myelin sheaths form around demyelinated axons. Recent studies in an animal model of Dem have demonstrated that Metformin (Met) can reverse damage and restore the regenerative capacity of oligodendrocyte precursor cells (OPCs), improving REM. Additionally, Met has an effect on increasing mitochondrial bioenergetics.
Wistar rats were treated with Cuprizone (CPZ) and CPZ plus Met using two routes of administration: oral and intraperitoneal. Data obtained during Rem showed that in both routes, Met significantly reduces astrogliosis and microgliosis in the corpus callosum, along with a higher number of OLm compared to the spontaneous Rem condition without Met. Plasma extracellular vesicles (pEVs) were isolated from control and Dem animals to study their effect on OLs in primary cultures and were characterized by Nano Particle Analysis Tracking (NTA). Preliminary results show that pEVs from animals that received CPZ show a delay in OL maturation, suggesting a role of pEVs in the perpetuation and maturation failure typical of the disease.