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Age-dependent effect of continuous ‘artificial light at night’ on circadian rhythm in male rats: neuroprotective role of melatonin

Abstract

Circadian disruption due to artificial light at night (ALAN) is an alarming threat to modern society. In the present study we evaluated the protective effect of melatonin on age dependent redox insults and neurochemical deficits induced by ALAN in the brain of chronodisrupted rat model. Young (3 months) and old (22 months) male Wistar rats were exposed to ALAN along with melatonin supplementation (10 mg Kg−1, oral) for 10 days. Results demonstrated significant increment in the pro-oxidant biomarkers: reactive oxygen species, lipid hydroperoxidation, protein carbonyl, nitric oxide while suppression in the total thiol, ferric reducing antioxidant potential level, superoxide dismutase and catalase activities in the brain of ALAN exposed groups with higher amplitude in aged rats. Further these oxidative modifications were protected by subsequent administration of melatonin. Mitochondrial complexes (C-I to C-IV) activity was significantly altered in young and old ALAN exposed groups with melatonin showing protective effect. Histopathological analysis show dense cytosolic staining and neuronal degeneration in cerebral cortex and different hippocampus regions with greater extent in old ALAN rats effectively moderated by melatonin supplementation. RT-PCR data analysis revealed melatonin effectively downregulated neuroinflammatory (IL-6, TNF α) and neurodegenerative marker (Ngb) while upregulating the aging (Sirt 1) gene expression in both young and old melatonin supplemented ALAN exposed groups. Our results may help in understanding the degree of ALAN induced photo-oxidative damage in neuronal redox homeostasis during aging. We also show that melatonin supplementation might provide a basis for amelioration of oxidative disturbances to improve circadian entrainment in aged populations.

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Acknowledgements

AKV is a recipient of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. Financial funding from Department of Biotechnology, Govt. of India under the ‘Research Resources, Service Facilities and Platforms’ is gratefully acknowledged. The Department of Biochemistry is supported by FIST Grant of DST, New Delhi and SAP DRS I from UGC, India.

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AKV and SIR conceived and designed the experiments. AKV and SS performed the experiments. AKV, SS and SIR analyzed the data. SS and SIR contributed with reagents/materials/analysis tools. AKV and SIR wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Syed Ibrahim Rizvi.

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Verma, A.K., Singh, S. & Rizvi, S.I. Age-dependent effect of continuous ‘artificial light at night’ on circadian rhythm in male rats: neuroprotective role of melatonin. Biogerontology 22, 531–545 (2021). https://doi.org/10.1007/s10522-021-09933-y

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Keywords

  • Aging
  • Artificial light at night (ALAN)
  • Brain
  • Chronodisruption
  • Melatonin
  • Oxidative stress