From the Research
Role of Melatonin in Treating Neuroinflammation
- Melatonin has been shown to modulate neuroinflammatory response and microglial activation in mice exposed to dim blue light at night, reducing hippocampal microglial activation and the expression of inflammatory factors IL-1β and TNF-α 1.
- Melatonin enhances microglia M2 polarization in rat models of neuro-inflammation via regulating ER stress/PPARδ/SIRT1 signaling axis, inhibiting NFκB-IKKβ activation in primary microglia 2.
- Melatonin attenuates neuroinflammation by down-regulating NLRP3 inflammasome via a SIRT1-dependent pathway in MPTP-induced models of Parkinson's disease, alleviating motor dysfunction and preventing MPTP-induced neurotoxicity in dopaminergic neurons 3.
- Melatonin acts as an antidepressant via attenuation of neuroinflammation by targeting Sirt1/Nrf2/HO-1 signaling, improving depressive-like behaviors and reducing cytokines level, oxidative stress, and glial cell activation markers in the brain of mice 4.
- Melatonin has been suggested as a potential regulator of oxidative stress and neuroinflammation, with implications for the management of brain injury-induced neurodegeneration, regulating TBI-induced autophagic dysfunction, mitogen-activated protein kinases, and release of inflammatory cytokines 5.
Mechanisms of Melatonin in Neuroinflammation
- Melatonin's anti-inflammatory effects are mediated by its receptor MT2, which downregulates the expression of inflammatory proteins P-P65 and NLRP3, inhibiting CD80 expression and M1-type activation in microglia 1.
- Melatonin regulates microglial polarization through the ER-stress-dependent PPARδ/SIRT1 signaling cascade, boosting LPS-stimulated alterations in polarization from the M1 to the M2 phenotype 2.
- Melatonin negatively regulates NLRP3 inflammasome activation via a SIRT1-dependent pathway, restoring the downregulation of SIRT1 and attenuating the activation of the NLRP3 inflammasome in MPP+-primed BV2 cells 3.
- Melatonin receptor-dependently protects against LPS-induced depressive-like behaviors via counteracting LPS-induced neuroinflammation, reducing oxidative stress and normalizing LPS-altered Sirt1, Nrf2, and HO-1 expression 4.
Implications of Melatonin in Neuroinflammation
- Melatonin may be a useful therapeutic approach for the treatment of neuroinflammation-associated disorders, such as Parkinson's disease and depression 1, 2, 3, 4.
- Melatonin's regulatory effects against TBI-induced autophagic dysfunction, mitogen-activated protein kinases, and release of inflammatory cytokines suggest its potential in managing brain injury-induced neurodegeneration 5.