New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. © 2016 Wiley Periodicals, Inc.
© 2016 Wiley Periodicals, Inc.
A: Adult neurogenesis occurs in two regions: the subgranular zone (SGZ) and the subventricular zone (SVZ). B: In the SVZ, neural progenitor cells (type B cells) give rise to type C cells, which differentiate to neuroblasts (type A cells). Type A cells migrate via the rostral migratory stream (RMS) and differentiate into neurons in the olfactory bulb (OB). Neuroblasts migrate via the RMS to the olfactory bulb and generate new neurons. C: In the SGZ, glial-like radial stem cells known as Type-I cells express glial fibrillary acidic protein (GFAP) and nestin. They divide to produce intermediate stage progenitors (Type-II cells), which then undergo further rounds of cell division to generate neuroblasts and post-mitotic immature granule neurons. Type II cells express Sox2, while neuroblast and immature neurons express doublecortin (DCX), PSA-NCAM, and calretinin. Mature neurons are defined by expression of NeuN.