Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Prog Neurobiol. 2019 Feb;173:54-87. doi: 10.1016/j.pneurobio.2018.06.002. Epub 2018 Jun 8.
Mood disorders are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although over the past 40 years the biogenic amine models have provided meaningful links with the clinical phenomena of, and the pharmacological treatments currently employed in, mood disorders, there is still a need to examine the contribution of other systems to the neurobiology and treatment of mood disorders. This article reviews the current literature describing the potential role of nitric oxide (NO) signaling in the pathophysiology and thereby the treatment of mood disorders. The hypothesis has arisen from several observations including (i) altered NO levels in patients with mood disorders; (ii) antidepressant effects of NO signaling blockers in both clinical and pre-clinical studies; (iii) interaction between conventional antidepressants/mood stabilizers and NO signaling modulators in several biochemical and behavioral studies; (iv) biochemical and physiological evidence of interaction between monoaminergic (serotonin, noradrenaline, and dopamine) system and NO signaling; (v) interaction between neurotrophic factors and NO signaling in mood regulation and neuroprotection; and finally (vi) a crucial role for NO signaling in the inflammatory processes involved in pathophysiology of mood disorders. These accumulating lines of evidence have provided a new insight into novel approaches for the treatment of mood disorders.
心境障碍是一种慢性、复发性精神疾病，影响着全球数百万人。尽管在过去的 40 年中，生物胺模型为心境障碍的临床现象和目前使用的药理学治疗提供了有意义的联系，但仍有必要研究其他系统对心境障碍的神经生物学和治疗的贡献。本文综述了目前描述一氧化氮（NO）信号在心境障碍的病理生理学中的潜在作用，从而为心境障碍的治疗提供了新的思路。这一假说源于以下几个观察结果：（i）心境障碍患者的 NO 水平改变；（ii）NO 信号阻断剂在临床和临床前研究中的抗抑郁作用；（iii）在几项生化和行为研究中，传统抗抑郁药/心境稳定剂与 NO 信号调节剂之间的相互作用；（iv）单胺能（血清素、去甲肾上腺素和多巴胺）系统与 NO 信号之间的生化和生理相互作用的证据；（v）神经递质和 NO 信号在心境调节和神经保护中的相互作用；最后（vi）NO 信号在涉及心境障碍病理生理学的炎症过程中的关键作用。这些不断增加的证据为心境障碍的治疗提供了新的思路。
