Involvement Of Hypothalamic Neuropeptide Y In Depression Induced By Chronic Unpredictable Stress

Depression is a kind of mood disorder, primarily characterized by low mood,loss of interest and lack of pleasure. The occurrence of depression is considered to berelated with genetic, neural-biochemical and psychosocial factors. With the ascendingincidence of depression caused by exacerbation of social factors, the study on thepathogenesis and prevention of depression has long been a hotspot in neurologicalresearch.The hypothalamo-pituitary-adrenal(HPA) axis is one of the main modulator forthe homeostasis of body. The hyperactivity of HPA axis by long-term stress results inhigh glucocorticoid(GC) secreting, which caused a series of pathologic changes, suchas depression, hypertention and diabetes and stress ulcer, et al. So with the gradualdeepening of the studies on the pathogenesis of depression, more attentions are paidfor the role of NPY in the modulating of emotion and stress-related diseases.However, the molecular mechanisms underlying the effect of NPY on HPA axis areyet to be fully elucidated.The present study was aimed to investigate the role of NPY in the depressioninduced by chronical unpredictable stress (CUS). Intra-PVN injection of NPY wasconducted by stereotaxic coordinates. The behavior changes were determined bysucrose preference test and forced swimming test. The levels of serum ACTH andCORT were conducted by radio immunoassay (RIA). The expression of GR in PVNwas detected by western blot.The results showed that compared with control rats, rats receiving CUS for21days presented depression-like behaviors, including a reduction of body weight andsucrose preference, increased serum level of ACTH and CORT, increased duration ofimmobility in forced swimming test, and decreased expression of GR in cells of PVN.Intra-PVN injection of NPY increase the GR expression in PVN, the growth rate ofbody weight and sucrose preference, decrease the serum level of ACTH and CORT.These data suggest that CUS might induce depression by down-regulating theexpression of GR in the PVN. Antidepressant effect of NPY was mainly through up-regulating the GR in the PVN.