Neural stem cell deforestation as the main force driving the age-related decline in adult hippocampal neurogenesis

Deforestation is such a great word because it implies that we should be able to seed new neurons if we can figure out the best growth factors.
http://www.sciencedirect.com/science/article/pii/S0166432811007285

Abstract

Newborn neurons derived from radial glia-like stem cells located in the dentate gyrus integrate into the adult hippocampal circuitry and participate in memory formation, spatial learning, pattern separation, fear conditioning, and anxiety. This process takes place throughout the life span of mammals, including humans; however, it follows a sharp declining curve. New neurons are generated abundantly during youth but very scarcely in the aged brain. The absolute number of newly generated neurons, or neurogenic output, is determined at different levels along the neurogenic cascade: the activation of quiescent stem cells; the mitotic potential of proliferating precursors; and the survival of neuronal fate-committed precursors. A continuous depletion of the hippocampal neural stem cell pool has been recently proposed as the main force underlying the age-related decline of neurogenesis, in contrast to the previous view of population of neural stem cells whose number remains constant but loses its ability to bear fruit. Nevertheless, the diminished neurogenic output may be reflecting other phenomena such as decreased mitotic capability of proliferating progenitors, decreased survival or changes in differentiation. We describe herein the most important events in determining the amount of neurogenesis in the dentate gyrus and examine the literature to understand the effects of age throughout the cascade.

Highlights

► The adult hippocampal neurogenic output is determined at different levels. ► The neurogenic output declines with age. ► A depletion of activated neural stem cells explains the age-related neurogenic decline. ► Two hypotheses, “deforestation” versus “sterilization” might explain the depletion.

Abbreviations: ANPs, amplifying neural progenitors; BLBP, brain lipid binding protein; BrdU, 5-bromo-2′-deoxy-uridine; DG, dentate gyrus; FGF-2, Fibroblast Growth Factor 2; GFAP, glial fibrillary acidic protein; GFP, green fluorescent protein; IGF-1, Insulin Growth Factor 1; NBs, neuroblasts; NMDA, N-acetyl-d-aspartate; OB, olfactory bulb; PSA-NCAM, polysialated neural cell adhesion protein; QNPs, quiescent neural progenitors; RMS, rostral migratory stream; ROS, reactive oxygen species; SGZ, subgranular zone; SVZ, subventricular zone; TERC, telomerase RNA component; TERT, telomerase reverse transcriptase; VEGF, Vascular Endothelial Growth Factor

Keywords: Adult neurogenesis; Neural stem cells; Hippocampus; Aging; Astrocytes

Article Outline

• 1. Neurogenesis in the adult hippocampus and aging
• 2. Neural stem cell activation
• 3. Proliferation of ANPs
• 4. Survival of neuroblasts and immature neurons
• 5. Conclusions and areas of future research
• Acknowledgements
• References