Rostro-Caudal Gradual Loss of Cellular Diversity Within the Periventricular Regions of the Ventricular System

Abstract

Neurogenesis occurs constitutively within the periventricular region (PVR) of the lateral ventricles (LV) of the adult mammalian brain. The occurrence of adult neurogenesis within the PVR outside the neurogenic niche of the LV remains controversial, but neural stem cells can be isolated from PVR of the whole ventricular system. The histological basis of this phenomenon including the regional differences of cellular phenotypes within the PVRs is still enigmatic. The occurrence of neurogenesis or manipulable progenitor cells in caudal parts of the adult brain is however one prerequisite for orthotopic regenerative approaches in Parkinson's disease (PD) and other disorders of the midbrain/brainstem. Using quantitative immunohistochemical techniques and electron microscopy, we found a rostro-caudal gradual loss of cellular diversity within the PVR throughout the whole ventricular axis with loss of transit amplifying epidermal growth factorreceptor 1 type C cells in all parts caudal to the LV, a gradual reduction from rostral to caudal of both stem cells (type B cells or astrocytes) without signs of proliferation outside the PVR of the LV as well as neuroblasts-like cells (polysialylated neural cell adhesion molecule [PSA-NCAM] 1 , but doublecortin negative cells) with a different morphology compared with neuroblasts of the PVR of the LV. Electron microscopy confirmed these immunohistochemical data. The proportion of Nestin 1 /CD24 1 cells and Nestin 1 /S100b 1 ependymal cells were consecutively increased in the PVR from rostral to caudal, and ultrastructural analysis showed a region-specific morphology with darker cytoplasm with occasional large lipid droplets as well as indented nuclei within the caudal PVRs. The strong correlation of neuroblast-like cells with the number of neurosphere-forming cells suggests that a quiescent subtype of PSA-NCAM 1 cells might be a source of neurosphere-forming cells. We did not find any evidence for neurogenesis or the occurrence of neuroprogenitors within the substantia nigra or other parts of the midbrain/brainstem outside the PVR. Our data provide the histological framework for future studies on orthotopic regenerative approaches in PD by recruiting endogenous predopaminergic progenitors from the midbrain PVR. STEM CELLS 2009;27:928-941 Disclosure of potential conflicts of interest is found at the end of this article.

Oxygen Tension Within the Neurogenic Niche Regulates Dopaminergic Neurogenesis in the Developing Midbrain

“…However, further studies are warranted to investigate whether the observed changes in dopaminergic neurogenesis translate into functional changes of the dopaminergic system in the postnatal and/or adult brain. Detailed knowledge of the composition of the midbrain neurogenic niche harboring dopaminergic NPC capacity will eventually help to develop restorative strategies for neurodegenerative diseases such as Parkinson's disease by both recruitment of endogenous progenitor cells from the niche [50][51][52] and improvement of dopaminergic cell graft. Our study, therefore, provides the initial framework for future studies on the molecular mechanisms mediating oxygen regulation of dopaminergic neurogenesis within the midbrain neurogenesis as its natural environment.…”

Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain

“…Abundant production of new neurons in the adult mammalian brain is limited to the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles in the forebrain (Alvarez-Buylla and Lim, 2004;Thored et al, 2007;Frielingsdorf et al, 2004;Hermann et al, 2009;Zhao et al, 2003). Neurogenesis may be evoked in quiescent regions, but the number of persisting new neurons that are generated remains low and consequently the functional recovery of the animals limited (Lindvall et al, 2004).…”

Roles of PPAR transcription factors in the energetic metabolic switch occurring during adult neurogenesis

“…6), since it has been demonstrated that there is a rostro-caudal gradual loss of neurogenic potential within the periventricular germinal region. 30 The choice of the mouse as model to study the PPARg and neurogenesis was due to the difficulties to obtain healthy human brain slices, particularly at subventricular level. Figure 6 shows PPARg immunolocalization along the anterior-posterior and dorsal-ventral axes of LV.…”

“…Therefore, it is apparent that PPARg immunoreactivity decreases along the anterior-posterior axis together with the neurogenic potential. 30 In order to correlate the nuclear staining of PPARg to the neurogenic niche, the co-expression of this transcription factor with markers of different stages of neurogenesis was studied (Fig. 7).…”

“…30 To evaluate which cellular types are able to store glycogen in the SVZ and the possible correlation between glucose metabolism and neurogenesis, glycogen was examined together with PPARg, GFAP and bIII-tubulin, the latter 2 being markers of astrocyte and young neurons respectively. …”