Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment.
Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and mice lacking neurotrophin-4 (NT-4-/-) together with their wild-type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and enriched NT-4-/- mice showed a two-fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU-positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice. Failure to up-regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required for the environmental induction of neurogenesis.
Rossi
Chiara
C
Istituto di Neuroscienze C.N.R., via G. Moruzzi 1, 56100 Pisa, Italy.
Angelucci
Andrea
A
Costantin
Laura
L
Braschi
Chiara
C
Mazzantini
Mario
M
Babbini
Francesco
F
Fabbri
Maria Elena
ME
Tessarollo
Lino
L
Maffei
Lamberto
L
Berardi
Nicoletta
N
Caleo
Matteo
M
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004777:Environment; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000172:deficiency; D009474:Neurons / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; C073922:neurotrophin 4