Melatonin improves neuroplasticity by upregulating the growth‐associated protein‐43 (<scp>GAP</scp>‐43) and<scp>NMDAR</scp>postsynaptic density‐95 (<scp>PSD</scp>‐95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long‐term recovery period

Juan, Wei-Sheng; Huang, Shih‐Hung; Chang, Chia Ling; Hung, Yao-Min; Lin, Yu‐Wen; Chen, Tsung-Ying; Lee, Ai-Hua; Lee, Ai-Chiang; Wu, Tong; Lee, E-Jian

doi:10.1111/jpi.12114

Cited by 51 publications

(48 citation statements)

References 54 publications

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“…For example, melatonin may prevent oxidative damage in a model of focal ischemia by enhancing the nuclear factor erythroid 2-related factor 2 and antioxidant-responsive element (Nrf2-ARE) signaling pathway [219]. Moreover, melatonin may prevent glutamate excitotoxicity by up-regulating the growthassociated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins, thereby enhancing neuroplasticity [221]. Melatonin may also prevent ER stress [222] In a multicenter RCT melatonin combined with buspirone was effective for the acute treatment of MDD [223].…”

Section: Melatoninmentioning

confidence: 98%

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Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets

Carvalho¹,

Miskowiak²,

Hyphantis³

et al. 2015

CNSNDDT

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Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

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Section: Melatoninmentioning

confidence: 98%

“…The neuroprotective effects of melatonin have been extensively investigated [219][220][221]. For example, melatonin may prevent oxidative damage in a model of focal ischemia by enhancing the nuclear factor erythroid 2-related factor 2 and antioxidant-responsive element (Nrf2-ARE) signaling pathway [219].…”

Section: Melatoninmentioning

confidence: 99%

Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets

Carvalho¹,

Miskowiak²,

Hyphantis³

et al. 2015

CNSNDDT

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show abstract

“…Recently, the antioxidant effects of melatonin-induced neural plasticity have been investigated and other studies have reported the effects of melatonin on neuroplasticity and brain remodeling [49]. According to former researchers, melatonin seems to more effectively prevent lipid peroxidation in vivo [50], indicating that an even higher concentration of melatonin is thought to be required to exert its antioxidative role in vitro conditions compared to in vivo.…”

Section: Introductionmentioning

confidence: 99%

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

Won

Jin

Choi

et al. 2017

IJMS

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Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation (fmr) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.

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“…And overproduction of ROS due to the lack of FMRP has observed in Fmr1 KO mice. Eventually, these events affect neural signaling, learning and memory problem caused by altered antioxidant system [44]. Recently, melatonin has been investigated in neuronal plasticity with its antioxidant effect.…”

Section: Introductionmentioning

confidence: 99%

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

Won

Jin

Lee

et al. 2017

Preprint

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Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

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Cited by 51 publications

References 54 publications

Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets

Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

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