Targeted transgene expression in neuronal precursors: watching young neurons in the old brain

Progress in the field of neurogenesis is limited by the lack of animal models allowing direct detection and analysis of living cells participating in neurogenesis. We engineered a transgenic mouse model that expresses the fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp...

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Bibliographic Details
Published in:The European journal of neuroscience 2006-09, Vol.24 (6), p.1535-1545
Main Authors: Couillard-Despres, Sebastien, Winner, Beate, Karl, Claudia, Lindemann, Gudrun, Schmid, Peter, Aigner, Robert, Laemke, Joern, Bogdahn, Ulrich, Winkler, Juergen, Bischofberger, Josef, Aigner, Ludwig
Format: Article
Language:English
Subjects:
adult neurogenesis
Age Factors
Animals
Blotting, Western - methods
Bromodeoxyuridine - metabolism
Carbocyanines - metabolism
doublecortin
fluorescent reporter protein
Gene Expression - physiology
Glial Fibrillary Acidic Protein - metabolism
Green Fluorescent Proteins - biosynthesis
Hippocampus - cytology
Immunohistochemistry - methods
In Vitro Techniques
Intermediate Filament Proteins - metabolism
Luminescent Proteins - metabolism
Membrane Potentials - physiology
Membrane Potentials - radiation effects
Mice
Mice, Transgenic
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Nerve Tissue Proteins - metabolism
Nestin
neural stem cell
neuronal migration
Neurons - physiology
Neuropeptides - genetics
Neuropeptides - metabolism
Patch-Clamp Techniques - methods
Promoter Regions, Genetic - physiology
transgenic mouse
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Summary:Progress in the field of neurogenesis is limited by the lack of animal models allowing direct detection and analysis of living cells participating in neurogenesis. We engineered a transgenic mouse model that expresses the fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp. reef coral red fluorescent protein under the control of the doublecortin (DCX) promoter, a gene specifically and transiently active in neuronal precursors and young neurons. The expression of the reporter proteins correlated with expression of the endogenous DCX protein, and with developmental and adult neurogenesis. Neurogenesis was unaffected by the presence of the fluorescent proteins. The transgenic mice allowed direct identification of the very few newly generated neurons present in the aged brain. We performed electrophysiological analysis and established that newly generated hippocampal granule cells in aged and young mice shared identical physiological properties. Hence, although the rate of neurogenesis tapers with ageing, a population of highly excitable young neurons indistinguishable to those found in younger animals is continuously generated. Therefore, maintenance of the fundamental properties of neuronal precursors even at advanced age suggests that stimulation of neurogenesis may constitute a valid strategy to counteract age‐related neuronal loss and cognitive declines.
ISSN:0953-816X
1460-9568
DOI:10.1111/j.1460-9568.2006.05039.x