The activation of metabotropic glutamate receptor subtype 3 modulates the expression of CD44 receptor in astrocytes.

FERNÁNDES, ROCÍO A.; RUDI, M. ; VITALE, DAIANA L.; DURAND, D.; PALUMBO, MARÍA LAURA

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Anual de SOCIEDADES DE BIOCIENCIA; 2019

The glutamatergic transmission has been postulated as the pathologic base of several degenerative disorders. The prevention of excitotoxicity by subtypes 2/3 metabotropic glutamate receptors (mGluR) activation is considered promising in psychiatry. The astrocytes present mGlu3R and remove the glutamate from the synaptic space through specific transporters, thereby avoiding excitotoxicity resulting from glutamate excess. Furthermore, strong positive correlations were found between CD44 (transmembrane receptor for the glycosaminoglycan hyaluronan (HA)) and genes of the glutamate?glutamine cycle typically expressed in astrocytes. Following damage in the central nervous system, HA (main component of the extracellular matrix in the brain) is synthesized at high levels by reactive astrocytes. HA is synthesized by HA synthases (HAS 1-3) and degraded by hyaluronidases (Hyal 1-3). The aim of this work is to study the expression of the CD44, HAS and Hyal and the HA levels in cortical astrocytes of rats in presence of LY379268 (agonist of mGlu3R). The cortices of postnatal P0-2 Wistar rats were cultivated during 3 weeks to obtain a culture of astrocytes, which were treated with (+LY) and without (-LY) 0.1 uM LY379268 during 24 h. We found a decrease in the expression of CD44 in astrocytes +LY (p = .033, n=4) respect to ?LY analyzed by RT-qPCR. However, no significant differences were observed in the Hyal 3 expression between astrocytes +LY and ?LY. Hyal 1-2 and HAS 1-3 mRNA levels were undetectable. The HA levels in astrocytes supernatants +LY and ?LY did not show significant differences by ELISA. We conclude that the activation of mGlu3R by LY379268 in astrocytes modulates the expression of CD44 by decreasing its levels. However, it did not affect HAS, Hyal or HA levels. This astrocyte-mediated mechanism could play an important role in the neurodegenerative disease promoting minor adhesion to the extracellular matrix and contribute to improve their excitotoxicity function.