Melatonin exerts neuroprotection in a chronodisrupted rat model through reduction in oxidative stress and modulation of autophagy

ABSTRACT

Circadian disruption due to artificial light affects cellular redox homeostasis and may lead to neurodegenerative diseases. The aim of the present study was to investigate the effect of continuous light exposure (CLE) and continuous dark exposure (CDE) along with melatonin supplementation on neuronal redox status, mitochondrial complexes, membrane bound transporters, inflammation, autophagy and neurodegeneration in chronodisrupted model of rat. In the study artificial light of white LED bulb with 500 lux intensity was used. Melatonin (10 mg/kg b.w., orally) was supplemented to control and CLE groups for 10 days. Standard protocols were employed to measure pro-oxidants, non-enzymatic antioxidants, and mitochondrial complexes in brain tissues. Membrane-bound ion transporter activities were evaluated in the crude synaptosomes. Gene expression analysis was performed to assess the expression of inflammatory, autophagy and neuronal marker genes. Histopathological changes in cerebral cortex and different hippocampus regions of the brain were studied. Melatonin exerted a significant normalization of redox status biomarkers in brain tissue. Further melatonin restored the activities of mitochondrial complexes and synaptosomal membrane bound ion transporters. RT-PCR data revealed that melatonin downregulated the expression of inflammatory (TNF-α, IL-6) autophagy (Atg-3, Beclin-1) and neurodegenerative genes (Ngb and NSE) in CLE group. Melatonin also preserved the histology architecture in cerebral cortex and hippocampus. Our results indicate that melatonin exerts a potent neuroprotective effect through reduction of oxidative stress, inflammation and autophagy. Melatonin supplementation might be a promising neurotherapeutic in the treatment neurodegenerative disorders caused by circadian disturbances.

KEYWORDS:

• Brain
• circadian disruption
• melatonin
• neurodegeneration
• oxidative stress

Acknowledgements

AKV is a recipient of fellowship from the Council of Scientific and Industrial Research (CSIR), New Delhi, India. Financial funding from Department of Biotechnology, Government of India under the RRFSP is gratefully acknowledged. The Department of Biochemistry is supported by FIST grant of DST, New Delhi and SAP DRS I from UGC, India.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Science and Engineering Research Board.