Antiinflammatory Activity of Melatonin in Central Nervous System

Abstract

Melatonin is mainly produced in the mammalian pineal gland during the dark phase. Its secretion from the pineal gland has been classically associated with circadian and circanual rhythm regulation. However, melatonin production is not confined exclusively to the pineal gland, but other tissues including retina, Harderian glands, gut, ovary, testes, bone marrow and lens also produce it. Several studies have shown that melatonin reduces chronic and acute inflammation. The immunomodulatory properties of melatonin are well known; it acts on the immune system by regulating cytokine production of immunocompetent cells. Experimental and clinical data showing that melatonin reduces adhesion molecules and pro-inflammatory cytokines and modifies serum inflammatory parameters. As a consequence, melatonin improves the clinical course of illnesses which have an inflammatory etiology. Moreover, experimental evidence supports its actions as a direct and indirect antioxidant, scavenging free radicals, stimulating antioxidant enzymes, enhancing the activities of other antioxidants or protecting other antioxidant enzymes from oxidative damage. Several encouraging clinical studies suggest that melatonin is a neuroprotective molecule in neurodegenerative disorders where brain oxidative damage has been implicated as a common link. In this review, the authors examine the effect of melatonin on several neurological diseases with inflammatory components, including dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, stroke, and brain ischemia/reperfusion but also in traumatic CNS injuries (traumatic brain and spinal cord injury)

Redox regulation of cellular stress response in multiple sclerosis

“…However, up-regulation of antioxidants in astrocytes and macrophages in active MS lesions [30] as well as in leukocytes suggests that endogenous protection from oxidative damage could limit the deleterious consequences of the oxidative stress per se [40]. Interestingly, exogenously administrated antioxidants have shown some beneficial effects in animal studies of MS but no clinical studies support the use of such therapy [41][42][43][44]. Furthermore, the possible links between MS and redox balance perturbation is indicated by increased malonaldehyde and F2-iP levels in MS patients as compared to control individuals with other neurological disorders [11] and, in addition, an inappropriate expression of Hsps on oligodendrocytes [36,45].…”

Inflammation and the Silent Sequelae of Stroke

“…The quality of these studies, however, has been suboptimal and the evidence is not yet compelling enough to suggest that antidepressants be prescribed to all patients with PSD [106]. Non-SSRI antidepressants have not been widely studied in stroke, but drugs like agomelatine may be particularly attractive given that melatonin decreases central nervous system inflammation [107] and improves outcome in experimental models of cerebral ischemia [108,109]. Additional evidence for the role of inflammation in the genesis of PSD and as a viable target for the treatment of PSD includes the fact that treatment with pioglitazone, as opposed to metformin, decreases PSD in patients with diabetes [110].…”

Trening ute eller inne? Rapport fra et prosjekt med datainnsamling under Forskningsdagene 2012

“…Moreover, it has an antioxidant action, scavenging free radicals, stimulating antioxidant enzymes, enhancing the activities of other antioxidants or protecting other antioxidant enzymes from oxidative damage. Several studies suggest that melatonin is a neuro-protective molecule in neurodegenerative disorders where brain oxidative damage has been implicated as a common link (Esposito & Cuzzocrea, 2010). Reduced MLT production has been associated with coronary-vascular-diseases (CVDs), diabetes (Peschke, 2008;Ruger & Scheer, 2009), different forms of cancer (Takeda & Maemura, 2010), neurological diseases with inflammatory components including dementia, Alzheimer disease, Parkinson disease, stroke, and brain ischemia/reperfusion (Esposito & Cuzzocrea, 2010).…”