| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Experimental Gerontology | ||||
| Publisher: | PERGAMON-ELSEVIER SCIENCE LTD | ||||
| Place of Publication: | OXFORD | ||||
| Volume: | 57 | ||||
| Page Range: | pp. 149-154 | ||||
| Date: | 2014 | ||||
| Institutions: | Medicine > Lehrstuhl für Neurologie | ||||
| Identification Number: |
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| Keywords: | GROWTH-FACTOR-BETA; STEM-CELL; HIPPOCAMPAL NEUROGENESIS; ADULT NEUROGENESIS; DENTATE GYRUS; RATS; DEPLETION; BRAIN; NICHE; POOL; Neurogenesis; Aging; Proliferation; TGF-beta signaling; Smad; Neural stem cell | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 61196 |
Web of ScienceAbstract
We recently reported that young (3 to 4 months old) mice lacking Exon 1 of the Smad7 gene (S7 Delta Ex1 mice) show enhanced proliferation of neural stem and progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) and in the subventricular zone (SVZ) of the lateral ventricles. It remained unclear, however, whether this phenotype would persist along aging, the latter typically being ...
Abstract
We recently reported that young (3 to 4 months old) mice lacking Exon 1 of the Smad7 gene (S7 Delta Ex1 mice) show enhanced proliferation of neural stem and progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) and in the subventricular zone (SVZ) of the lateral ventricles. It remained unclear, however, whether this phenotype would persist along aging, the latter typically being associated with a profound decrease in neurogenesis. Analysis of NPCs' proliferation based on the cell cycle marker PCNA in 12 month-old S7 Delta Ex1 mice revealed a reversal of the phenotype. Hence, in contrast to their younger counterparts, 12 month-old S7 Delta Ex1 mice had a reduced number of proliferating cells, compared to wildtype (WT) mice. At the same time, the survival of newly generated cells was enhanced in the aged transgenic animals. 12 month-old S7 Delta Ex1 mice further displayed a reduced level of neurogenesis based on the numbers of cells expressing doublecortin (DCX), a marker for newborn neurons. The reduced neurogenesis in aged S7 Delta Ex1 mice was not due to a stem cell depletion, which might have occurred as a consequence of hyperproliferation in the young mice, since the number of Nestin and Sox2 positive cells was similar in WT and S7 Delta Ex1 mice. Instead, Nestin positive cells in the DG as well as primary neurosphere cultures derived from 12 month-old S7 Delta Ex1 mice had a reduced capability to proliferate. However, after passaging, when released from their age-and niche-associated proliferative block, neurospheres from aged S7 Delta Ex1 mice regained the hyperproliferative property. Further, pSmad2 antibody staining intensity was elevated in the DG and SVZ of 12-month old transgenic compared to WT mice, indicating increased intracellular TGF-beta signaling in the aged S7 Delta Ex1 mice. In summary, this points toward differential effects of S7 Delta Ex1 on neurogenesis: (i) a hyperproliferation in young animals caused by a cell autonomous mechanism, and (ii) a TGF-beta dependent modulation of neurogenesis in aged S7 Delta Ex1 animals that abrogates the cell-intrinsic hyperproliferative properties and results in reduced proliferation, increased stem cell quiescence, and enhanced survival of newly generated cells. (C) 2014 The Authors. Published by Elsevier Inc.
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