title: Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.
abstract: Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (P<0.001). Plasma CORT levels were increased in male CUS rats (P=0.001), while male MDD patients did not show a significant change in cortisol levels. In conclusion, the changes in plasma and hypothalamic NOS-NO of CUS rats and MDD were similar. The male CUS rat model may thus help us with our investigation of the mechanism underlying NOS-NO alterations in depression.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China; Lab of Neurosurgery, Institute of Nervous System Diseases, Xuzhou Medical College, Xuzhou 221004, Jiangsu, PR China.
authors.forename: Shang-Feng
authors.initials: SF
authors.lastname: Gao
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China; Department of Psychiatry, The Second Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310009, Zhejiang, PR China.
authors.forename: Yun-Rong
authors.initials: YR
authors.lastname: Lu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China.
authors.forename: Li-Gen
authors.initials: LG
authors.lastname: Shi
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China.
authors.forename: Xin-Yan
authors.initials: XY
authors.lastname: Fu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Luo
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China; Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, PR China. Electronic address: baoaimin@zju.edu.cn.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Bao
mesh_terms: D000328:Adult; D000818:Animals; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006854:Hydrocortisone
keywords: Chronic unpredictable stress; Major depressive disorder; Nitric oxide; Nitric oxide synthase 1; Paraventricular nucleus