Local Melatonin Regulates Inflammation Resolution: A Common Factor in Neurodegenerative, Psychiatric and Systemic Inflammatory Disorders
Local Melatonin Regulates Inflammation Resolution: A Common Factor in Neurodegenerative, Psychiatric and Systemic Inflammatory Disorders
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DOI：
10.2174/1871527313666140711091400
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发表时间：
2014-01-01
影响因子：
3
通讯作者：
Maes, Michael
中科院分区：
文献类型：
--
作者：
Anderson, George;Maes, Michael
在许多精神疾病、神经退行性疾病和全身炎症性疾病中，昼夜褪黑激素减少，而褪黑激素酶和褪黑激素受体是遗传易感性因素。用褪黑激素治疗可用于多种医学病症，包括双相情感障碍、阿尔茨海默病、抑郁症和纤维肌痛。褪黑激素作用的减少通常归因于松果体产生的损失。然而，褪黑激素，沿着其直接前体N-乙酰血清素（NAS），由许多（如果不是全部的话）含有线粒体的细胞产生，包括免疫细胞和中央神经胶质。在这里，我们回顾了本地褪黑激素和NAS生产的数据，并提出星形胶质细胞褪黑激素和NAS流出是至关重要的局部中枢炎症调节在神经胶质细胞-神经元界面。褪黑激素和NAS提供抗氧化和抗炎作用，以及增加线粒体氧化磷酸化和功能。因此，它们在局部炎症部位的产生减少被认为是褪黑激素与各种医疗条件的遗传关联的基础。类似地，包括抗抑郁药在内的5-羟色胺增强药物在各种疾病中的益处部分是通过增加星形胶质细胞局部NAS和褪黑激素产生的5-羟色胺可用性来介导的。这种概念化结合了不同疾病的大量数据，特别是氧化和亚硝化应激、抗氧化剂、色氨酸催化酶和线粒体失调在不同的医疗条件下明显。胶质细胞褪黑素和NAS调节是精神疾病、神经退行性疾病和胶质瘤的重要治疗靶点。
In many psychiatric, neurodegenerative and systemic inflammatory disorders circadian melatonin is decreased whilst melatonin enzymes and melatonin receptors are genetic susceptibility factors. Treatment with melatonin is useful in a diverse range of medical conditions, including bipolar disorder, Alzheimer's disease, depression and fibromyalgia. Decreased melatonin effects are classically attributed to lost pineal production. However, melatonin, along with its immediate precursor N-acetylserotonin (NAS), is produced by many, if not all, mitochondrial containing cells, including immune cells and central glia. Here we review the data on local melatonin and NAS production and propose that astrocyte melatonin and NAS efflux is crucial to local central inflammation regulation at the glia-neuronal interface. Melatonin and NAS provide antioxidant and anti-inflammatory effects, as well as increasing mitochondrial oxidative phosphorylation and functioning. Consequently, their decreased production at sites of local inflammation is proposed to underlie melatonin's genetic association with a diverse range of medical conditions. Similarly the benefits of serotonin boosting medications, including antidepressants, across a wide range of conditions are partly mediated by increasing serotonin availability for astrocytic local NAS and melatonin production.Such a conceptualization incorporates a plethora of data across different disorders, especially the commonalities in oxidative and nitrosative stress, anti-oxidants, tryptophan catabolites and mitochondrial dysregulation evident in a diverse array of medical conditions. Glia melatonin and NAS regulation are important treatment targets in psychiatric disorders, neurodegenerative disorders and glioma.