Mechanisms of Inhibition of Excessive Microglial Activation by Melatonin

Gao, Juan; Su, Gang; Liu, Jifei; Zhang, Jiajia; Zhou, Jian; Liu, Xiaoyan; Tian, Ye; Zhang, Zhenchang

doi:10.1007/s12031-020-01531-w

Cited by 13 publications

(12 citation statements)

References 85 publications

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“…With regard to this overwhelming evidence, an earlier cytokine-based conclusion that melatonin may not be an important modulator of macrophage and microglia function [ 60 ] appears to be obsolete. In addition to the many data concerning anti-inflammatory signaling within the microglial regulatory network, various studies have observed the suppression of microglia activation and microgliosis by melatonin under various conditions and often along with attenuated astrocyte activation [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Conversely, microglia activation can be aggravated by pinealectomy [ 71 ].…”

Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingmentioning

confidence: 99%

Melatonin and Microglia

Hardeland

2021

IJMS

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Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk with astrocytes and neurons, indirectly. These effects of melatonin are of relevance in terms of antioxidative protection, not only concerning free-radical detoxification, but also in prevention of processes that cause, promote, or propagate oxidative stress and neurodegeneration, such as overexcitation, toxicological insults, viral and bacterial infections, and sterile inflammation of different grades. The immunological interplay in the CNS, with microglia playing a central role, is of high complexity and includes signaling toward endothelial cells and other leukocytes by cytokines, chemokines, nitric oxide, and eikosanoids. Melatonin interferes with these processes in multiple signaling routes and steps. In addition to canonical signal transduction by MT1 and MT2 melatonin receptors, secondary and tertiary signaling is of relevance and has to be considered, e.g., via the upregulation of sirtuins and the modulation of pro- and anti-inflammatory microRNAs. Many details concerning the modulation of macrophage functionality by melatonin are obviously also applicable to microglial cells. Of particular interest is the polarization toward M2 subtypes instead of M1, i.e., in favor of being anti-inflammatory at the expense of proinflammatory activities, which is well-documented in macrophages but also applies to microglia.

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Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingmentioning

confidence: 99%

Melatonin and Microglia

Hardeland

2021

IJMS

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“…We next sought to elucidate the mechanisms by which Mt1 activation rescues neurons from undergoing Aβ-induced AD pathologies. In mammals, melatonin inhibits the activation of microglia 14,16 and stimulates Aβ-degrading enzyme expression, thus inhibiting Aβ deposition. 17,18,51 Therefore, melatonin effectively protects neurons from beta-amyloid-mediated toxicity by modulating the induced anti-amyloidogenic and anti-inflammatory processes.…”

Section: Activation Of Mt1 Via Crispr/cas9 Activators Modulates Anti-...mentioning

confidence: 99%

“…This hormone detoxifies reactive oxygen species and prevents the overactivation of microglia by inhibiting the phosphorylation of mTOR and its downstream matrix, thus inhibiting microglia activation. [14][15][16] Microglia overactivation greatly contributes to neuronal damage in neurodegenerative diseases. Therefore, these mechanisms could explain the neuroprotective properties of melatonin.…”

Section: Introductionmentioning

confidence: 99%

Activation of melatonin receptor 1 by CRISPR‐Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model

Park

Kim

2022

Journal of Pineal Research

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of neurotoxic beta-amyloid (Aβ) in the brain.Melatonin receptors have been reported to associate with aging and AD, and their expression decreased with the progression of AD. As an alternative to AD treatment, overexpression of melatonin receptors may lead to melatonin-like effects to treat alleviate the symptoms of AD. Here, we successfully activated the type 1 melatonin receptor (Mt1) in vivo brain using a Cas9 activator as a novel AD therapeutic strategy. The Cas9 activator efficiently activated the endogenous Mt1 gene in the brain. Activation of Mt1 via Cas9 activators modulated anti-amyloidogenic and anti-inflammatory roles in 5xFAD AD mice brain. Moreover, activation of Mt1 with the CRISPR/Cas9 activator improved cognitive deficits in an AD model. These results demonstrated the therapeutic potential of melatonin receptor activation via CRISPR/Cas9

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“…Moreover, cryopreservation induces ROS generation that finally leads to oxidative stress, which affects the recovery efficiency and clinical pregnancy rate ( Agarwal et al, 2012 ; Won et al, 2013 ; Grynberg et al, 2018 ; Van Den Heuvel-Eibrink et al, 2018 ; Pang et al, 2020 ). The production of ROS by oocytes and somatic cells and the reduced levels of antioxidant enzymes in the follicular microenvironment may induce follicular apoptosis ( Gao et al, 2020 ; Yang et al, 2020 ). Some antioxidants (such as MLT and resveratrol) have been shown to counteract the negative effects of cryopreservation on the quantity and quality of OTs, probably through the enhancement of free radical scavenging mechanisms in the follicles ( Tarín et al, 2002 ; Rocha et al, 2018 ; Olcese, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Melatonin Inhibits Oxidative Stress and Apoptosis in Cryopreserved Ovarian Tissues via Nrf2/HO-1 Signaling Pathway

Sun

Liu

Yang

et al. 2020

Front. Mol. Biosci.

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In the field of assisted reproductive technology, female fertility preservation, particularly ovarian tissue cryopreservation in adolescent cancer patients, has attracted much attention. Melatonin (MLT) is well known for its antioxidative and anti-apoptotic properties; however, whether it can ameliorate the cryoinjury and inhibit the generation of reactive oxygen species (ROS) in cryopreserved ovarian tissues (OTs) has not yet been reported. Here, we demonstrated that MLT could protect follicular integrity; prevent cell apoptosis; decrease ROS, malondialdehyde (MDA), and nitric oxide (NO) levels; and increase activities of glutathione peroxidases (GSH-Px), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) in cryopreserved OTs. Furthermore, these effects may be related with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, as evidenced by increased mRNA levels of Nrf2 downstream genes, including heme oxygenase-1 (HO-1), glutathione S-transferase M1 (GSTM1), SOD, and CAT. In summary, MLT can not only directly scavenge ROS but also significantly induce the activation of antioxidative enzymes via the Nrf2 signaling pathway, which is a new mechanism underlying the protection effects of MLT on cryopreserved OTs.

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Mechanisms of Inhibition of Excessive Microglial Activation by Melatonin

Cited by 13 publications

References 85 publications

Melatonin and Microglia

Melatonin and Microglia

Activation of melatonin receptor 1 by CRISPR‐Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model

Melatonin Inhibits Oxidative Stress and Apoptosis in Cryopreserved Ovarian Tissues via Nrf2/HO-1 Signaling Pathway

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