Circumventricular organs: A novel site of neural stem cells in the adult brain

Abstract

Neurogenesis in the adult mammalian nervous system is now well established in the subventricular zone of the anterolateral ventricle and subgranular zone of the hippocampus. In these regions, neurons are thought to arise from neural stem cells, identified by their expression of specific intermediate filament proteins (nestin, vimentin, GFAP) and transcription factors (Sox2). In the present study, we show that in adult rat and mouse, the circumventricular organs (CVOs) are rich in nestin + , GFAP + , vimentin + cells which express Sox2 and the cell cycle-regulating protein Ki67. In culture, these cells proliferate as neurospheres and express neuronal (doublecortin + , β-tubulin III + ) and glial (S100β + , GFAP + , RIP + ) phenotypic traits. Further, our in vivo studies using bromodeoxyuridine show that CVO cells proliferate and undergo constitutive neurogenesis and gliogenesis. These findings suggest that CVOs may constitute a heretofore unknown source of stem/progenitor cells, capable of giving rise to new neurons and/or glia in the adult brain.

Glial and Perivascular Structures in the Subfornical Organ

“…Nestin has been shown to form co-polymers with vimentin (Eliasson et al 1999;Marvin et al 1998;Menet et al 2001). Bennett et al (2009) found that neurospheres can develop in vitro from nestin-containing SFO cells (also immunopositive for GFAP and vimentin), and that S100-immunopositive cells took up bromdeoxyuridine, indicating neurogenesis. The long processes we observed may have a guidance function, like radial glia, in this case.…”

“…We also investigated staining for vimentin and nestin, proteins that occur in immature glia (Dahl et al 1981;Hockfield and McKay 1985;Zerlin et al 1995). Nestin may be particularly relevant, as it has recently been reported to play a role in adult neurogenesis in the circumventricular organs (Bennett et al 2009;Sanin et al 2013;Wei et al 2002).…”

Stem Cell Therapy: A Promising Therapeutic Approach for Multiple Sclerosis

“…These neurogenic niches are composed of a heterogeneous population of NSC that is able to self-renew and give rise to most of the neuronal and glial precursors (4). Several studies showed that the third ventricle and hypothalamus neurogenic zone contain multipotent cells that can give rise to neurons, oligodendrocytes, and astrocytes in vitro and in vivo (169)(170)(171). Xu and others reported that the third ventricle ependymal layer cells were able to migrate into hypothalamic parenchymal regions and differentiate into functional neurons in response to injury (172).…”

Regulation of Body Weight and Metabolism by Tanycyte-Derived Neurogenesis in Young Adult Mice

“…The ME, for instance, lies outside the blood-brain barrier; it is thus exposed to higher effective concentrations of circulating dietary and hormonal cues than the hypothalamic parenchyma (Fry et al 2007;Langlet et al 2013b). In contrast, all tanycyte subtypes directly contact the cerebrospinal fluid (CSF) and can potentially respond to intracerebral ventricular signals (Bennett et al 2009;Bolborea and Dale 2013).…”