Increased generation of granule cells in adult Bcl-2-overexpressing mice: a role for cell death during continued hippocampal neurogenesis

Kuhn, H. Georg and Biebl, Manfred and Wilhelm, Daniel and Li, M. and Friedlander, R. M. and Winkler, Juergen (2005) Increased generation of granule cells in adult Bcl-2-overexpressing mice: a role for cell death during continued hippocampal neurogenesis. EUROPEAN JOURNAL OF NEUROSCIENCE, 22 (8). pp. 1907-1915. ISSN 0953-816X,

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Abstract

Programmed cell death is an important mechanism during brain development in order to control neuronal cell numbers and to correctly form neuronal circuitries. Programmed cell death is also present in neurogenic regions of the adult brain, and a significant portion of the adult-born cells is eliminated during the first months of maturation. We here address the question whether overexpression of the anti-apoptotic protein Bcl-2 would improve the survival of neural progenitor cells and, as a consequence, increase neurogenesis in the adult hippocampus. Transgenic animals, which express human Bcl-2 under the neuron-specific enolase promoter (NSE-huBcl-2), show a significant reduction of apoptotic cells in the hippocampal granule cell layer to about half of the wild-type level. These apoptotic cells are almost exclusively found in the zone of hippocampal progenitor activity and frequently co-label with the neuronal progenitor marker doublecortin (DCX). The rate of adult neurogenesis is doubled in the dentate gyrus of Bcl-2-overexpressing mice as demonstrated by quantification of progenitor cells using DCX and new neurons using bromodeoxyuridine (BrdU)/neuronal nuclei antigen (NeuN) double-labelling. The effect of Bcl-2 is limited to the late phase of progenitor maturation, as proliferation and early-phase progenitor cells were not affected. The increased level of neurogenesis leads to a significantly higher total number of granule cells in the dentate gyrus. These results underline the importance of developmental cell death during neurogenesis in the adult brain.

Item Type: Article
Uncontrolled Keywords: BCL-2 PROTEIN EXPRESSION; LONG-TERM SURVIVAL; NEURAL STEM-CELLS; RAT DENTATE GYRUS; TRANSGENIC MICE; OLFACTORY-BULB; COGNITIVE DECLINE; NERVOUS-SYSTEM; FAMILY-MEMBERS; NEURONS; dentate gyrus; neuronal differentiation; neuronal progenitor; programmed cell death; proliferation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Apr 2021 08:02
Last Modified: 26 Apr 2021 08:02
URI: https://pred.uni-regensburg.de/id/eprint/35557

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