Chronic Stress-induced Depression In Hippocampal Neuropeptide Y And Nitric Oxide Synthase

Depression, a kind of mental disease, is closely related to stress, and with an ascending incidence year by year along with the exacerbation of social factors, such as the accelerating pace of modern life and the increasingly fierce competition. It is thus important to reveal the mechanism of depression. The hippocampus has recently attracted tremendous attention for the study of depression. Accumulated evidence indicates that neuropeptide Y is involved in coping with a wide range of stressors, and that impaired central NPY signalling could be involved in the pathophysiology of depression. Antidepressant treatment has been reported to increase the expression of the NPY gene in hippocampus. A variety of studies also suggest a role of nitric oxide (NO) in brain impairment produced by chronic stress. Chronic stress can increase expression of nitric oxide synthase (NOS) in hippocampus. However, it is unclear the relationship between the hippocampal NPY and NOS in depression induced by chronic unpredictable mild stress (CUMS). To investigate the relationship between NPY and NOS in depression induced by CUMS. CUMS-induced depression model was established in Sprague-dawley rats. Intrahippocampal injection of NPY, NPY-Y1 receptor antagonist GR231118 and non-specific NOS inhibitor L-NAME was respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by sucrose consumption test, open field test and forced swimming test. The expression of neuronal nitric oxide synthase, inducible nitric oxide synthase (iNOS) and NPY in hippocampus was detected by immunohistochemistry.The results showed that compared with the control group,receiving CUMS for 21 days or intrahippocampal injection of GR231118 significant reduction in body weight, and induced depression-like behavioral changes, including a reduction in sucrose preference, body weight, locomotor activity, rearing and grooming in open field test, and increased duration of immobility in forced swimming test, the expression of NPY significantly decreased (P<0.01), but the expression of NOS increased obviously in the hippocampal CA3 region and DG region (P<0.01). Intra-hippocampal microinjections of NPY prevented the change of CUMS-induced depression-like behavior and decreased the expression nNOS and iNOS in the hippocampal CA3 region and DG region (P<0.01). Intra-hippocampal microinjections of a selective NPY-Yl receptor antagonist reduced behavioral ability of the rats dramatically and the significantly increased expression of NOS (P<0.01). Intra-hippocampal microinjections of L-NAME improved the depression-like behavioral changes induced by CUMS or intra-hippocampal microinjection of NPY-Y1 receptor inhibitor GR231118. In conclusion, reduced expression of NPY and an increase in expression of NOS in hippocampus may make significant contributions to CUMS-induced depression. This study suggest that the antidepressant function of NPY associates with down-regulation of NOS expression in hippocampus,which may be mediated via NPY Y1 receptor.