Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression

Abstract

Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers.

Melatonin and the Brain–Heart Crosstalk in Neurocritically Ill Patients—From Molecular Action to Clinical Practice

“…Its concentration in the blood depends on the circadian rhythm. The highest secretion from the pineal gland is observed at night [13,14]. Physiologically, melatonin is mainly secreted by the pineal gland.…”

“…Physiologically, melatonin is mainly secreted by the pineal gland. However, the intestines, skin, retina, testes, ovaries, glial and microglial cells, and lymphocytes can also synthetize and release melatonin [14][15][16][17]. Its production and metabolism depend on race, age, and gender, and the highest melatonin concentration was found in epidermis of a young African American population [18].…”

“…This process is regulated by the light/dark cycle, and blue light (i.e., light waves between 420 and 480 nm) plays a crucial role via suppression of arylalkyl-amine N-acetyltransferase (AANAT) (Figure 2). Therefore, melatonin synthesis is better at night and with dark condi-tions, whereas light inhibits its synthesis and secretion [14,15]. Next, 5-hydroxytryptophan is decarbonized to serotonin, which is subsequently transferred to melatonin (Figure 2).…”

“…amine N-acetyltransferase (AANAT) (Figure 2). Therefore, melatonin synthesis is better at night and with dark conditions, whereas light inhibits its synthesis and secretion [14,15]. Next, 5-hydroxytryptophan is decarbonized to serotonin, which is subsequently transferred to melatonin (Figure 2).…”

Constant light in early life induces fear-related behavior in chickens with suppressed melatonin secretion and disrupted hippocampal expression of clock- and BDNF-associated genes

“…Conversely, melatonin and its precursor 5-hydroxytryptamine (5-HT) are related to improved behavior and wellbeing in both mammalian [ 16 ] and avian [ 17 ] species. Melatonin is reported to play important roles in regulating circadian clock, alleviating depression and anxiety, and mitigating oxidation-induced injuries [ 18 , 19 ].…”