Melatonin Attenuates Thrombin-induced Inflammation in BV2 Cells and Then Protects HT22 Cells from Apoptosis

Tang, Jiao; Chen, Rui; Wang, Lingling; Lu, Yu; Zuo, Dandan; Cui, Guiyun; Xiao-qian, Gong

doi:10.1007/s10753-020-01270-5

Cited by 12 publications

(10 citation statements)

References 36 publications

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“…In the latter study, conditioned medium from thrombin-treated BV2 cells was also shown to induce apoptosis in HT22 cells, an effect suppressed by the addition of melatonin. Similar protection was obtained with the antioxidant N -acetylcysteine, which may indicate a role of ROS scavenging [ 34 ]. The prevention of microglial inflammasome activation may be largely explained by the downregulation of TLR4 (toll-like receptor 4) [ 35 , 36 , 37 , 38 ] and its adapter protein MyD88 (myeloid differentiation factor 88) [ 36 ], effects that have been observed in very different models and under various conditions.…”

Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingsupporting

confidence: 58%

“…Suppression of the formation and activity of the NLRP3 inflammasome caused by melatonin was observed after LPS treatment in natural microglia in vivo [ 32 ] and in BV2 cells [ 33 ] as well as in an inflammation model of intracerebral hemorrhage in which BV2 cells were treated with thrombin [ 34 ]. In the latter study, conditioned medium from thrombin-treated BV2 cells was also shown to induce apoptosis in HT22 cells, an effect suppressed by the addition of melatonin.…”

Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingmentioning

confidence: 99%

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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 Signalingsupporting

confidence: 58%

Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingmentioning

confidence: 99%

Melatonin and Microglia

Hardeland

2021

IJMS

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“…The RBC-lysate model could well-mimic ICH condition in vitro, and it has not been previously used to assess neuroprotective effects of melatonin. Previous studies used oxyhemoglobin, hemin and thrombin as in vitro models of ICH (32,47,48). Using the RBC-lysate model, our results demonstrated that 10 -5 M melatonin could significantly increase viability of SH-SY5Y cells after RBC lysate treatment.…”

Section: Discussionmentioning

confidence: 52%

Melatonin attenuates microglial activation and improves neurological functions in rat model of collagenase-induced intracerebral hemorrhage

Leung¹,

Cheung²

2021

Melatonin Res.

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Intracerebral hemorrhage (ICH) is a severe form of stroke with a high mortality rate. It is also an important cause of permanent disability. Apart from hematoma growth and edema development, inflammatory responses and oxidative stress are responsible for poor outcomes after ICH. Due to its antioxidant, anti-inflammatory and anti-apoptotic properties, melatonin is a neuroprotective molecule against different neurological diseases. The protective roles of melatonin on ICH, particularly in the collagenase-induced ICH model, have not been well studied. The present study aims to explore neuroprotective effects of melatonin against ICH. At 24 hours after ICH induction, rats exhibited neurological deficits with mild loss in body weight (BW). Hematoma was found in the brain parenchyma with ED-1+ activated microglia and TUNEL+ apoptotic cells in the perihematomal region. As an in vitro model of ICH, SH-SY5Y cells were treated with red blood cell lysate. This treatment significantly reduced cell viability; however, melatonin (10-5 M) restored the cell viability. At 72 hours after ICH, rats treated with melatonin (50 mg/kg) at 2, 24 and 48 hours had reduced perihematomal microglial activation. However, there was no effect on hematoma size or perihematomal apoptosis. We further treated rats with 50 mg/kg melatonin starting at 2 hours and repeating at 24-hour intervals for two or seven more days. Both melatonin treatments improved post-ICH neurological functions, and the effect was most pronounced at 4 days after ICH. Since studies regarding the protective roles of melatonin on ICH remain very limited, our study advances our understanding of the potential use of melatonin as a treatment for ICH.

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“…Melatonin is a neurohormone secreted by pineal and initially recognized as an antioxidant and a powerful free radical scavenger implicated in various physiological and pathological processes (Tang et al, 2020). Its ability to readily cross the blood-brain barrier (BBB) enables a neuroprotective effect on central nervous system in a myriad of neurological diseases; e.g.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity

et al. 2021

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Stroke is one of the leading causes of death and disability worldwide with limited therapeutic options. Melatonin can attenuate ischemic brain damage with improved functional outcomes. However, the cellular mechanisms of melatonin-driven neuroprotection against post-stroke neuronal death remain unknown. Here, distal middle cerebral artery occlusion (dMCAO) was performed in C57BL/6j mice to develop an ischemic stroke in vivo model. Melatonin was injected intraperitoneally immediately after ischemia, and 24 and 48 hours later. Melatonin treatment, with 5 to 20 mg/kg, elicited a dose-dependent decrease in infarct volume and concomitant increase in sensorimotor function. At the molecular level, phosphorylation of PTEN and Akt were increased, whereas PTEN activity was decreased in melatonin treated animals 72 hours after dMCAO. At the cellular level, oxygenglucose deprivation (OGD) challenge of neuronal cell line Neuro-2a (N2a) and primary neurons supported melatonin’s direct protection against neuronal cell death. Melatonin treatment reduced LDH release and neuronal apoptosis at various time points, markedly increased Akt phosphorylation in neuronal membrane, but significantly suppressed it in the cytoplasm of post-OGD neurons. Mechanistically, melatonin-induced Akt phosphorylation and neuronal survival was blocked by Wortmannin, a potent PIP3 inhibitor, exposing increased PI3K/Akt activation as a central player in melatonin-driven neuroprotection. Finally, PTEN knock-down through siRNA significantly inhibited PI3K/Akt activation and cell survival following melatonin treatment, suggesting that melatonin protection against ischemic brain damage, is at least partially, dependent on modulation of the PTEN/PI3K/Akt signaling axis.

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Melatonin Attenuates Thrombin-induced Inflammation in BV2 Cells and Then Protects HT22 Cells from Apoptosis

Cited by 12 publications

References 36 publications

Melatonin and Microglia

Melatonin and Microglia

Melatonin attenuates microglial activation and improves neurological functions in rat model of collagenase-induced intracerebral hemorrhage

Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity

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