Brain-derived neurotropic factor and neurogenesis in the adult rat dentate gyrus: interactions with corticosterone.

Flattening the diurnal corticosterone rhythm prevented the stimulating action of L-NAME (a nitric oxide synthase, NOS, inhibitor) on progenitor cell proliferation in the dentate gyrus in Lister-Hooded adult male rats. The increased expression of brain-derived neurotrophic factor (BDNF) and trkB mRNA in the dentate gyrus which otherwise occurred after L-NAME was also prevented by clamping the corticoid rhythm in adrenalectomized rats, but was restored by daily additional injections of corticosterone (which replicates the diurnal rhythm). Unilateral infusions of BDNF into the lateral ventricle increased proliferation in the dentate gyrus on the side of the infusion, but this was not observed following implantation of subcutaneous corticosterone, which flattened the diurnal corticosterone rhythm. 5HT1A mRNA in the dentate gyrus was increased on both sides of the brain by unilateral BDNF infusions, but this was also prevented by subcutaneous corticosterone pellets. These results show that the diurnal rhythm of corticosterone regulates the stimulating action of NOS inhibitors on BDNF as well as on neurogenesis in the dentate gyrus, and that BDNF becomes ineffective on both proliferation rates and 5HT1A expression in the absence of a rhythm in corticosterone. This, together with our previous findings, suggests that corticoid rhythms permit both serotonin and NO access to BDNF, and the latter to regulate progenitor cell activity.