p75 neurotrophin receptor regulates basal and fluoxetine-stimulated hippocampal neurogenesis

• DOI: 10.1007/s00221-009-1947-6
• Publication Date: 2009-07-20T07:18:48Z
• Authors: Michael J. Colditz; Vibeke S. Catts; Noura Al-menhali; Geoffrey W. Osborne; Perry F. Bartlett; Elizabeth J. Coulson
• Keywords: Male; 572; Neurogenesis; Antidepressant; Cell Count; Receptors, Nerve Growth Factor; Hippocampus; Mice; 03 medical and health sciences; C1; Fluoxetine; Animals; Flow cytometry; Mice, Knockout; Neurons; Analysis of Variance; 0303 health sciences; Neurotrophin receptor; Flow Cytometry; Mice, Inbred C57BL; BDNF; Bromodeoxyuridine; Dentate Gyrus; NGFR; Antidepressive Agents, Second-Generation; 920111 Nervous System and Disorders; 1109 Neurosciences

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.