Reactive Astrocytes as Therapeutic Targets for Brain Degenerative Diseases: Roles Played by Metabotropic Glutamate Receptors

Talia M Planas-Fontánez,Cheryl F Dreyfus,Kyle S Saitta

doi:10.1007/s11064-020-02968-6

Abstract

Astrocytes are well known to play critical roles in the development and maintenance of the central nervous system (CNS). Moreover, recent reports indicate that these cells are heterogeneous with respect to the molecules they express and the functions they exhibit in the quiescent or activated state. Because astrocytes also contribute to pathology, promising new results raise the possibility of manipulating specific astroglial populations for therapeutic roles. In this mini-review, we highlight the function of metabotropic glutamate receptors (mGluRs), in particular mGluR3 and mGluR5, in reactive astrocytes and relate these to three degenerative CNS diseases: multiple sclerosis, Alzheimer’s disease and Amyotrophic Lateral Sclerosis. Previous studies demonstrate that effects of these receptors may be beneficial, but this varies depending on the subtype of receptor, the state of the astrocytes, and the specific disease to which they are exposed. Elucidating the role of mGluRs on astrocytes at specific times during development and disease will provide novel insights in understanding how to best use these to serve as therapeutic targets.

Highlights

It is well recognized that astrocytes play a number of critical roles that support the developing and mature brain
The Group I/ Group II metabotropic glutamate receptors (mGluRs) agonist trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) injected directly into the cuprizone-induced lesion increases synthesis and release of brain-derived neurotrophic factor (BDNF), an effect that is blocked when BDNF was selectively deleted from astrocytes, suggesting that the mGluRs mediate the increase in this trophic factor in astrocytes [50]
II agonist enhances glial-derived neurotrophic factor (GDNF) release from cultured wild-type astrocytes through mGluR3. It is not yet known if astrocytes are responsible for the effects observed in h SOD1G93A mice. This mini-review has documented a number of studies that suggest the possible importance of astrocytes as therapeutic targets in treatment of central nervous system (CNS) disease

Summary

Introduction

It is well recognized that astrocytes play a number of critical roles that support the developing and mature brain. We focus this mini-review on roles played by metabotropic glutamate receptors (mGluRs) that are expressed on astrocytes during disease. As indicated in this mini-review, astrocytes whether quiescent or reactive are highly heterogeneous populations with respect to their response to the local central nervous system (CNS) region in which they reside, and the specific diseases or injuries to which they are exposed.

Results

Conclusion