Melatonin Modulates Neuroinflammatory Response and Microglial Activation in Mice Exposed to Dim Blue Light at Night

Overview

Journal Front Pharmacol

Date 2024 Jun 14

PMID 38873431

Authors

Chao Song

Zhaotaize Suo

Zixu Wang

Jing Cao

Yulan Dong

Yaoxing Chen

Affiliations

Soon will be listed here.

Abstract

Objectives: Dim light at night contributes to neurodegenerative diseases by causing neuroinflammation. In the central nervous system, the activation of microglia is a significant contributor to neuroinflammation. Therefore, there is an urgent need to find an intervention to treat the neuroinflammatory response caused by dim light at night. Melatonin is a rhythmic hormone whose synthesis is suppressed during the day. In this study, we attempt to explore whether and how melatonin improves hippocampal neuroinflammation in mice exposed to dim blue light at night.

Materials And Methods: , a total of 36 male C57BL6/J mice that exposed to no light at night, dim blue light at night, and dim blue light at night with melatonin treatment. , the corticosterone-induced BV2 cells with or without melatonin treatment were used.

Results: Both and experiments showed melatonin treatment significantly reduced dim blue light -induced hippocampal microglial activation and the expression of inflammatory factors IL-1β and TNF-α. This improved effect of melatonin is related to its receptor MT2 rather than MT1. The MT2 blockers significantly increased mRNA levels of M1-type activation marker CD86 and inflammatory cytokines IL-1β and TNF-α in melatonin-treated BV2 cells. Binding of melatonin to its receptor MT2 downregulated the expression of inflammatory proteins P-P65 and NLRP3, consequently inhibited the CD80 expression and M1-type activation in microglia. Furthermore, consistent with the decrease in microglial activation and inflammatory response after melatonin treatment, we also observed a reduction in hippocampal neuron loss and damage to the HT22 cells.

Conclusion: Our findings suggested that melatonin may regulate microglial polarization through MT2/NF-kB-NLRP3 pathway and improves dim blue light -induced hippocampal neuroinflammation in mice.

References

Tang J, Chen R, Wang L, Yu L, Zuo D, Cui G . Melatonin Attenuates Thrombin-induced Inflammation in BV2 Cells and Then Protects HT22 Cells from Apoptosis. Inflammation. 2020; 43(5):1959-1970. DOI: 10.1007/s10753-020-01270-5. View

Rasia-Filho A, Calcagnotto M, von Bohlen Und Halbach O . Glial Cell Modulation of Dendritic Spine Structure and Synaptic Function. Adv Neurobiol. 2023; 34:255-310. DOI: 10.1007/978-3-031-36159-3_6. View

Fonken L, Kitsmiller E, Smale L, Nelson R . Dim nighttime light impairs cognition and provokes depressive-like responses in a diurnal rodent. J Biol Rhythms. 2012; 27(4):319-27. DOI: 10.1177/0748730412448324. View

Feng X, Zhao Y, Yang T, Song M, Wang C, Yao Y . Glucocorticoid-Driven NLRP3 Inflammasome Activation in Hippocampal Microglia Mediates Chronic Stress-Induced Depressive-Like Behaviors. Front Mol Neurosci. 2019; 12:210. PMC: 6727781. DOI: 10.3389/fnmol.2019.00210. View

Zheng R, Ruan Y, Yan Y, Lin Z, Xue N, Yan Y . Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson's Disease. J Inflamm Res. 2021; 14:3063-3075. PMC: 8275196. DOI: 10.2147/JIR.S317672. View

Hardeland R . Melatonin and Microglia. Int J Mol Sci. 2021; 22(15). PMC: 8347578. DOI: 10.3390/ijms22158296. View

Wang X, Wang Z, Cao J, Dong Y, Chen Y . Melatonin ameliorates anxiety-like behaviors induced by sleep deprivation in mice: Role of oxidative stress, neuroinflammation, autophagy and apoptosis. Brain Res Bull. 2021; 174:161-172. DOI: 10.1016/j.brainresbull.2021.06.010. View

Liu Q, Wang Z, Cao J, Dong Y, Chen Y . Dim Blue Light at Night Induces Spatial Memory Impairment in Mice by Hippocampal Neuroinflammation and Oxidative Stress. Antioxidants (Basel). 2022; 11(7). PMC: 9311634. DOI: 10.3390/antiox11071218. View

Dong Y, Li S, Lu Y, Li X, Liao Y, Peng Z . Stress-induced NLRP3 inflammasome activation negatively regulates fear memory in mice. J Neuroinflammation. 2020; 17(1):205. PMC: 7341659. DOI: 10.1186/s12974-020-01842-0. View

10.

Jebelli J, Hooper C, Pocock J . Microglial p53 activation is detrimental to neuronal synapses during activation-induced inflammation: Implications for neurodegeneration. Neurosci Lett. 2014; 583:92-7. DOI: 10.1016/j.neulet.2014.08.049. View

11.

Fonken L, Lieberman R, Weil Z, Nelson R . Dim light at night exaggerates weight gain and inflammation associated with a high-fat diet in male mice. Endocrinology. 2013; 154(10):3817-25. DOI: 10.1210/en.2013-1121. View

12.

Xu Y, Cui K, Li J, Tang X, Lin J, Lu X . Melatonin attenuates choroidal neovascularization by regulating macrophage/microglia polarization via inhibition of RhoA/ROCK signaling pathway. J Pineal Res. 2020; 69(1):e12660. DOI: 10.1111/jpi.12660. View

13.

Gonzalez M . Dim Light at Night and Constant Darkness: Two Frequently Used Lighting Conditions That Jeopardize the Health and Well-being of Laboratory Rodents. Front Neurol. 2018; 9:609. PMC: 6084421. DOI: 10.3389/fneur.2018.00609. View

14.

Ali T, Rahman S, Hao Q, Li W, Liu Z, Shah F . Melatonin prevents neuroinflammation and relieves depression by attenuating autophagy impairment through FOXO3a regulation. J Pineal Res. 2020; 69(2):e12667. DOI: 10.1111/jpi.12667. View

15.

Silvani M, Werder R, Perret C . The influence of blue light on sleep, performance and wellbeing in young adults: A systematic review. Front Physiol. 2022; 13:943108. PMC: 9424753. DOI: 10.3389/fphys.2022.943108. View

16.

Calvo-Sanz J, Tapia-Ayuga C . Blue light emission spectra of popular mobile devices: The extent of user protection against melatonin suppression by built-in screen technology and light filtering software systems. Chronobiol Int. 2020; 37(7):1016-1022. DOI: 10.1080/07420528.2020.1781149. View

17.

Guo Y, Wei X, Zhang T, Sun T . Molecular mechanisms of melatonin-induced alleviation of synaptic dysfunction and neuroinflammation in Parkinson's disease: a review. Eur Rev Med Pharmacol Sci. 2023; 27(11):5070-5082. DOI: 10.26355/eurrev_202306_32624. View

18.

Chen R, Weitzner A, McKennon L, Fonken L . Light at night during development in mice has modest effects on adulthood behavior and neuroimmune activation. Behav Brain Res. 2021; 405:113171. PMC: 8120684. DOI: 10.1016/j.bbr.2021.113171. View

19.

Costello A, Linning-Duffy K, Vandenbrook C, Lonstein J, Yan L . Daytime Light Deficiency Leads to Sex- and Brain Region-Specific Neuroinflammatory Responses in a Diurnal Rodent. Cell Mol Neurobiol. 2022; 43(3):1369-1384. PMC: 10635710. DOI: 10.1007/s10571-022-01256-x. View

20.

Rumanova V, Okuliarova M, Zeman M . Differential Effects of Constant Light and Dim Light at Night on the Circadian Control of Metabolism and Behavior. Int J Mol Sci. 2020; 21(15). PMC: 7432546. DOI: 10.3390/ijms21155478. View