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. 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.
Couillard-Despres
Sebastien
S
Volkswagen-Foundation Junior Group, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
Winner
Beate
B
Karl
Claudia
C
Lindemann
Gudrun
G
Schmid
Peter
P
Aigner
Robert
R
Laemke
Joern
J
Bogdahn
Ulrich
U
Winkler
Juergen
J
Bischofberger
Josef
J
Aigner
Ludwig
L
D000367:Age Factors; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015870:Gene Expression / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D011401:Promoter Regions, Genetic / Q000502:physiology
D002232:Carbocyanines; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009479:Neuropeptides; C098830:TO-PRO-3; C413663:fluorescent protein 583; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine