29 Adult Human Neurogenesis: A Response to Cell Loss and New Circuitry Requirements?

Abstract

… the functional specialization of the brain imposes on the neurones two great lacunae; proliferation inability and irreversability of intraprotoplasmic differentiation. It is for this reason that, once the development was ended, the founts of growth and regeneration of axons and dendrites dried up irrevocably. In adult centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree.

Almost 100 years have past since santiago ramon y cajal wrote those words. In comparison, today there has been a giant paradigm shift from believing in a fixed and immutable brain structure to one of plasticity and one with neurogenic potential, even in the adult human brain. Although the exact functional significance remains to be fully appreciated, it is clear that the integration of new cells from the subventricular zone (SVZ) into the olfactory bulb (OB) or from the subgranule layer into the dentate gyrus (DG) allows mammals to engage in olfaction and in memory and learning. Despite these being vital for normal brain function, the most robust up-regulator of neurogenesis in humans is a response to neurodegeneration in specific brain regions. The specific and dramatic loss of striatal projection neurons in Huntington’s disease (HD), the specific loss of hippocampal cholinergic neurons in Alzheimer’s disease (AD), and the necrotic death of cells in the core and penumbral region of tissue beyond the point of vessel occlusion in stroke all lead to exacerbation...