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Abstract
Adult neurogenesis is
the process of creating new brain cells during adulthood. This involves
several stages including proliferation, migration, differentiation,
integration, and survival. G-protein-coupled receptors (GPCRs) regulate
this process in both neurogenic regions of the brain: the subgranular
and subventricular zones. The regulation of adult neurogenesis by GPCRs
holds therapeutic promise for many neuropathologies. Several GPCRs
activated by the neurotransmitters dopamine, glutamate, norepinephrine,
and serotonin were shown to regulate adult neurogenesis. Melatonin, a
neurohormone, and inflammatory molecules such as chemokines and
prostaglandins modulate different stages of neurogenesis through GPCRs
as well. The methods for studying the adult neurogenic stages depend
upon labeling of dividing cells using the synthetic thymidine analog,
nucleoside 5-bromo-2′-deoxyuridine (BrdU). BrdU incorporates into the
DNA, is transferred to daughter cells, and is labeled using antibodies.
The length of time after injection determines which stage of
neurogenesis is being examined. Additional methods include culture of
neonatal or adult neurospheres isolated from the subventricular zone,
monolayer cultures of isolated neural stem cells, as well as transgenic
manipulations via standard or viral-mediated techniques. In recent
years, the use of Cre-inducible transgenic animals has developed and led
to the creation of double- and triple-transgenic animals with specific
activation of receptors in selected cell types. Future work in GPCR
regulation of adult neurogenesis will likely include the use of
opsin-receptor chimeras allowing precise spatial and temporal activation
of GPCRs in neural stem/progenitor cells via optogenetics. This chapter
summarizes the roles of various GPCRs involved in the regulation of
adult neural stem cells and their progenitors and the current methods
used to examine the actions of GPCRs in adult neurogenesis.
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