The subventricular zone (SVZ) contains the largest pool of NSCs in the adult mammalian brain, including humans.
In rodents, the adult SVZ contains four distinct cell types defined by morphological, molecular markers, and electrophysiological properties: 1) neural progenitor (type A) cells express PSA-NCAM, Tuj1, and Hu; 2) NSCs in the SVZ are protoplasmic astrocytes (type B cells) and express nestin, vimentin and GFAP; 3) transit amplifying (type C) cells are nestin positive and form clusters adjacent to the chains of migrating neuroblasts throughout the SVZ; 4) ependymal ciliated (type E) cells separate the SVZ from the ventricular cavity (see figure).
The organization of the adult human SVZ is significantly different from that of rodents. In adult rodents, SVZ astrocytes (Type B cells) are located next to the ependymal layer. In contrast, in the adult human brain SVZ astrocytes are not found adjacent to the ependymal cells and no chains of migrating neuroblasts are found in this region. Instead, the cell bodies of human SVZ astrocytes accumulate in a band or ribbon separated from the ependymal layer by a gap that is largely devoid of cells (see figure).
Neural progenitors migrate from the SVZ through the rostral migratory stream (RMS), and after reaching the olfactory bulb (OB) they originate olfactory granule and periglomerular interneurons. Granule neurons are all GABAergic, whereas only 40% of the periglomerular neurons are GABAergic and, of those, 65% are also dopaminergic. Under normal conditions, neural progenitors in the SVZ remain as non-differentiated non-excitable cells. They begin to display properties of mature interneurons only on their arrival to the olfactory bulb. However, in humans, the extent of SVZ neurogenesis and the existence of the RMS are controversial.
The existence of functional adult neurogenesis in the SVZ raises the exciting possibility that manipulating endogenous neural progenitors may lead to successful cell replacement therapies for various degenerative neurological diseases, including Parkinson disease. Infusion of mitogens, growth factors or chemokines into the striatal parenchyma may activate the proliferation of neural stem cells in the SVZ and the migration of their progeny into the striatum to differentiate into dopaminergic neurons to replace the function of the degenerating nigrostriatal dopaminergic afferents.
The existence of functional adult neurogenesis in the SVZ raises the exciting possibility that manipulating endogenous neural progenitors may lead to successful cell replacement therapies for various degenerative neurological diseases, including Parkinson disease. Infusion of mitogens, growth factors or chemokines into the striatal parenchyma may activate the proliferation of neural stem cells in the SVZ and the migration of their progeny into the striatum to differentiate into dopaminergic neurons to replace the function of the degenerating nigrostriatal dopaminergic afferents.
References
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Arias-Carrión O, Freundlieb N, Oertel WH, Höglinger GU. Adult Neurogenesis and Parkinson’s disease. CNS Neurol Disord Drug Targets 6:326-35 (2007)
Arias-Carrión O, Drucker-Colín R. Neurogenesis as a therapeutic strategy to regenerate central nervous system. Rev Neurol 45: 739-745 (2007)
Arias-Carrión O. Basic mechanisms of rTMS: Implications in Parkinson's disease. Int Arch Med 1(1):2 (2008)
Yuan TF, Arias-Carrión O. Adult neurogenesis in the hypothalamus: Evidences, functions and implications. CNS Neurol Disord Drug Targets 10(4):433-439 (2011)
