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

Hermann, Andreas and Suess, Christian and Fauser, Mareike and Kanzler, Sylvia and Witt, Martin and Fabel, Klaus and Schwarz, Johannes and Höglinger, Günter U. and Storch, Alexander (2009) Rostro-Caudal Gradual Loss of Cellular Diversity Within the Periventricular Regions of the Ventricular System. Stem Cells, 27 (4). pp. 928-941. ISSN 1549-4918. https://resolver.caltech.edu/CaltechAUTHORS:20090831-081127186

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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 factor-receptor^+ 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]^+, but doublecortin negative cells) with a different morphology compared with neu^+/CD24^+ cells and Nestin^+/S100beta^+ 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^+ 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/stem.21DOIUNSPECIFIED
http://www3.interscience.wiley.com/journal/121671886/abstractPublisherUNSPECIFIED
Additional Information:© 2009 AlphaMed Press. Received: 14 October 2008; Accepted: 19 January 2009. First published online in STEM CELLS Express January 29, 2009. We thank Cornelia May and Doreen Streichert for excellent technical assistance and Martina Maisel and Chichung Lie for fruitful discussions. This work was supported in part by the Deutsche Parkinson-Gesellschaft (DPG) to A.H., by a Glaxo- SmithKline fellowship to A.H., the Medical Faculty Research Program MeDDrive to A.H., and by the Deutsche Forschungsgemeinschaft (DFG) through the DFG-Research Center for Regenerative Therapies Dresden (CRTD) to A.H and A.S.
Funders:
Funding AgencyGrant Number
Deutsche Parkinson-GesellschaftUNSPECIFIED
Glaxo-SmithKline fellowshipUNSPECIFIED
Medical Faculty Research Program MeDDriveUNSPECIFIED
Deutsche ForschungsgemeinschaftUNSPECIFIED
Research Center for Regenerative Therapies DresdenUNSPECIFIED
Subject Keywords:Adult neural stem cells; Midbrain neurogenesis; Parkinson's disease; Ventricular zone; Neuroepithelial cells
Issue or Number:4
Record Number:CaltechAUTHORS:20090831-081127186
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20090831-081127186
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15476
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:14 Sep 2009 18:43
Last Modified:03 Oct 2019 00:58

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