p75 neurotrophin receptor regulates basal and fluoxetine-stimulated hippocampal neurogenesis.
It is widely acknowledged that neurogenesis occurs in the adult hippocampus under normal conditions and that the rate can be regulated by environmental factors, including antidepressant drugs, with concomitant effects on behaviour. Using a quick and sensitive flow cytometry method that can assess changes in the number of bromodeoxyuridine (BrdU)-positive cells in hippocampus, in combination with traditional histological cell counts in the dentate gyrus, we report that mice lacking the p75 neurotrophin receptor gene (p75(NTR-/-)) have significantly reduced hippocampal neurogenesis. Chronic treatment with the antidepressant fluoxetine stimulated hippocampal cell proliferation in p75(NTR-/-) animals, but it did not result in an increase above basal levels of the number of newly born neurons in the dentate gyrus. These results indicate that p75(NTR) acts as a regulator of fluoxetine-stimulated as well as basal adult hippocampal neurogenesis.
Colditz
Michael J
MJ
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
Catts
Vibeke S
VS
Al-menhali
Noura
N
Osborne
Geoffrey W
GW
Bartlett
Perry F
PF
Coulson
Elizabeth J
EJ
D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D002452:Cell Count; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
D018687:Antidepressive Agents, Second-Generation; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D005473:Fluoxetine; D001973:Bromodeoxyuridine