Gao Shang-Feng, Lu Yun-Rong, Shi Li-Gen, Wu Xue-Yan, Sun Bo, Fu Xin-Yan, Luo Jian-Hong, Bao Ai-Min
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.
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.
Psychoneuroendocrinology. 2014 Sep;47:136-40. doi: 10.1016/j.psyneuen.2014.05.009. Epub 2014 May 22.
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.
一氧化氮（NO）和一氧化氮合酶-1（NOS1）参与应激反应和抑郁症。我们比较了暴露于慢性不可预测应激（CUS）的大鼠中NOS-NO的改变与人类重度抑郁症（MDD）的改变。在雄性CUS大鼠的下丘脑，我们测定了NOS活性，在室旁核（PVN），我们测定了NOS1免疫反应性（ir）细胞密度以及NOS1与应激相关神经肽促肾上腺皮质激素释放激素（CRH）、血管加压素（AVP）或催产素（OXT）的共定位。我们测量了未服用过药物的男性MDD患者的血浆NO水平和皮质醇，以及CUS大鼠的血浆NO和皮质酮（CORT）。在CUS大鼠中，下丘脑的总NOS活性（P = 0.018）和PVN中的NOS1-ir细胞密度均显著降低（P = 0.018），而该核中NOS1染色主要表达于OXT-ir神经元。有趣的是，雄性CUS大鼠（P = 0.001）和男性MDD患者（P < 0.001）的血浆NO水平均显著升高。雄性CUS大鼠的血浆CORT水平升高（P = 0.001），而男性MDD患者的皮质醇水平未显示出显著变化。总之，CUS大鼠和MDD患者血浆和下丘脑NOS-NO的变化相似。因此，雄性CUS大鼠模型可能有助于我们研究抑郁症中NOS-NO改变的潜在机制。
