G-protein-coupled receptors in adult neurogenesis

Abstract

The importance of adult neurogenesis has only recently been accepted, resulting in a completely new field of investigation within stem cell biology. The regulation and functional significance of adult neurogenesis is currently an area of highly active research. G-protein-coupled receptors (GPCRs) have emerged as potential modulators of adult neurogenesis. GPCRs represent a class of proteins with significant clinical importance, because approximately 30% of all modern therapeutic treatments target these receptors. GPCRs bind to a large class of neurotransmitters and neuromodulators such as norepinephrine, dopamine, and serotonin. Besides their typical role in cellular communication, GPCRs are expressed on adult neural stem cells and their progenitors that relay specific signals to regulate the neurogenic process. This review summarizes the field of adult neurogenesis and its methods and specifies the roles of various GPCRs and their signal transduction pathways that are involved in the regulation of adult neural stem cells and their progenitors. Current evidence supporting adult neurogenesis as a model for self-repair in neuropathologic conditions, adult neural stem cell therapeutic strategies, and potential avenues for GPCR-based therapeutics are also discussed.

Fig. 1.

Adult SVZ neurogenesis. B cells (purple) are astrocyte-like cells that serve as the SVZ stem cell (self-renews) and contact the ventricle lumen. C cells (light green) are rapidly dividing TAP cells derived through division from the B cells. C cells divide to generate committed A cells (blue), which are neuroblasts that migrate to the olfactory bulb, where they mature to become interneurons. Ependymal cells (gray) line the ventricle walls.

Fig. 2.

Adult SGZ neurogenesis. Astrocytes (AS; dark purple) self-renew and also divide to give rise to progenitors (D cells; blue), which differentiate into new granule cells (G cells; orange). These newly born granule cells integrate into the granule cell layer (brown G cells), where they form into mature granule cells (green). Blood vessels (BV; pink) are found close to the SGZ layer, and it is proposed that a perivascular basal lamina (BL; yellow cells) exists here similar to the ependymal cell layer found in the SVZ.