Pharmacological Effects of Melatonin as Neuroprotectant in Rodent Model: A Review on the Current Biological Evidence

Tan, Hui Ying; Ng, Khuen Yen; Koh, Rhun Yian; Chye, Soi Moi

doi:10.1007/s10571-019-00724-1

Cited by 22 publications

(18 citation statements)

References 219 publications

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“…An overwhelming amount of recent evidence points to melatonin’s neuroprotective effects in stroke, specifically highlighting its anti-oxidative, anti-inflammatory and anti-apoptotic capabilities, as shown in Table 1 . Importantly, melatonin can cross the blood brain barrier and attenuate neuronal cell death [ 57 ]. When melatonin was administered intraperitoneally to MCAO models, the brain infarct size decreased and cognitive performance was alleviated.…”

Section: Novel Evidence Supporting Melatonin As An Effective Theramentioning

confidence: 99%

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

et al. 2020

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Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system. Melatonin-based therapies have been shown to provide neuroprotective effects in the setting of ischemic stroke by mitigating neuroinflammation and accelerating brain tissue restoration. Melatonin treatment includes injection of exogenous melatonin, pineal gland grafting and melatonin-mediated stem cell therapy. This review will discuss the current preclinical and clinical studies investigating melatonin-based therapeutics to treat stroke.

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Section: Novel Evidence Supporting Melatonin As An Effective Theramentioning

confidence: 99%

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

et al. 2020

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“…Overall, our results on melatonin's effects are in agreement with its reported multiple beneficial actions that go well beyond a mere regulation of circadian rhythms. The compound is in fact endowed with anti-inflammatory, antioxidant, and neuroprotective activity against a number of neurodegenerative conditions that share neuroinflammatory features [35,91], including Parkinson's disease [92], hypoxia [29,93], amyotrophic lateral sclerosis [94], traumatic brain injury, spinal cord injury [95], and neuropsychiatric disor-ders [96]. A role for melatonin has convincingly emerged also in AD, where an inverse correlation between melatonin levels and disease progression has been reported in patients, along with sleep-wake cycle disturbances [43,97].…”

Section: Discussionmentioning

confidence: 99%

SIRT1-Dependent Upregulation of BDNF in Human Microglia Challenged with Aβ: An Early but Transient Response Rescued by Melatonin

et al. 2021

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Microglia represent a first-line defense in the brain. However, in pathological conditions such as Alzheimer’s disease (AD), a pro-inflammatory switch may occur, leading to loss of protective functions. Using the human microglial cell line HMC3, we showed that exposure to low concentrations of β-amyloid peptide 1-42 (Aβ42; 0.2 μM) initially (6 h) upregulated anti-inflammatory markers interleukin (IL)-4, IL-13, and brain-derived neurotrophic factor (BDNF). BDNF increase was prevented by selective inhibition of SIRT1 with EX527 (2 μM). Accordingly, these early effects were accompanied by a significant Aβ42-induced increase of SIRT1 expression, nuclear localization, and activity. SIRT1 modulation involved adenosine monophosphate-regulated kinase (AMPK), which was promptly (30 min) phosphorylated by Aβ42, while the AMPK inhibitor BML-275 (2 μM) attenuated Aβ42-induced SIRT1 increase. Initially observed microglial responses appeared transient, as microglial features changed when exposure to Aβ42 was prolonged (0.2 μM for 72 h). While SIRT1 and BDNF levels were reduced, the expression of inflammatory markers IL-1β and tumor necrosis factor (TNF)-α increased. This coincided with a rise in NF-kB nuclear localization. The effects of melatonin (1 μM) on prolonged microglial exposure to Aβ42 were analyzed for their protective potential. Melatonin was able to prolong SIRT1 and BDNF upregulation, as well as to prevent NF-kB nuclear translocation and acetylation. These effects were sensitive to the melatonin receptor antagonist, luzindole (25 μM). In conclusion, our data define an early microglial defensive response to Aβ42, featuring SIRT1-mediated BDNF upregulation that can be exogenously modulated by melatonin, thus identifying an important target for neuroprotection.

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“…However, there is an abundance of receptor-mediated neuroprotective effects that are amply reviewed recently elsewhere (please see refs. 74 , 75 ) so the remainder of the review will be focused on mitochondrial-mediated actions.…”

Section: Melatonin and Neuroprotectionmentioning

confidence: 99%

Melatonin’s neuroprotective role in mitochondria and its potential as a biomarker in aging, cognition and psychiatric disorders

et al. 2021

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Melatonin is an ancient molecule that is evident in high concentrations in various tissues throughout the body. It can be separated into two pools; one of which is synthesized by the pineal and can be found in blood, and the second by various tissues and is present in these tissues. Pineal melatonin levels display a circadian rhythm while tissue melatonin does not. For decades now, melatonin has been implicated in promoting and maintaining sleep. More recently, evidence indicates that it also plays an important role in neuroprotection. The beginning of our review will summarize this literature. As an amphiphilic, pleiotropic indoleamine, melatonin has both direct actions and receptor-mediated effects. For example, melatonin has established effects as an antioxidant and free radical scavenger both in vitro and in animal models. This is also evident in melatonin’s prominent role in mitochondria, which is reviewed in the next section. Melatonin is synthesized in, taken up by, and concentrated in mitochondria, the powerhouse of the cell. Mitochondria are also the major source of reactive oxygen species as a byproduct of mitochondrial oxidative metabolism. The final section of our review summarizes melatonin’s potential role in aging and psychiatric disorders. Pineal and tissue melatonin levels both decline with age. Pineal melatonin declines in individuals suffering from psychiatric disorders. Melatonin’s ability to act as a neuroprotectant opens new avenues of exploration for the molecule as it may be a potential treatment for cases with neurodegenerative disease.

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Pharmacological Effects of Melatonin as Neuroprotectant in Rodent Model: A Review on the Current Biological Evidence

Cited by 22 publications

References 219 publications

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

SIRT1-Dependent Upregulation of BDNF in Human Microglia Challenged with Aβ: An Early but Transient Response Rescued by Melatonin

Melatonin’s neuroprotective role in mitochondria and its potential as a biomarker in aging, cognition and psychiatric disorders

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