Inhibition of neuronal nitric oxide synthase enhances cell proliferation in the dentate gyrus of the adrenalectomized rat

Abstract Recent studies have demonstrated that the elimination of adrenal steroids by an adrenalectomy (ADX) increases the expression of neuronal nitric oxide synthase (NOS), and that it increases cell proliferation in the rat dentate gyrus. However, no evidence has been presented to date which indicates that NO regulates cell proliferation in the dentate gyrus of the adult rats. In this study, the effect of blocking NO production on ADX-induced increase of cell proliferation and serotonergic innervation was examined in the rat dentate gyrus. 7-nitroindazole (7-NI; 30 mg/kg, intraperitoneally), a selective inhibitor of neuronal NOS, was injected 1 day before an ADX and then once every 24 h for 4 days after the ADX subsequently. The proliferating cells were identified with 5-bromo-2-deoxyuridine (BrdU) immunostaining. Long-term inhibition of the neuronal NOS by 7-NI markedly increased the BrdU-labeled cell population density 4–18-fold in the dentate gyrus of the adrenalectomized rats compared to that in the vehicle-injected adrenalectomized rats. Immunoreactivity of serotonin, known as a mediator of granule cell genesis, was detected only in the dentate gyrus of 7-NI-injected adrenalectomized rats. These results indicate that NO may be involved in the cell proliferation in the dentate gyrus of the adrenalecomized rat and that serotonin may mediate the regulatory effect of NO on the cell proliferation in rat dentate gyrus.