Melatonin improves neuro-behavioral perturbations in diet/photoperiod induced chronodisruption

Abstract

Endogenous circadian oscillators regulate learning, cognitive performance and memory are disrupted due to circadian shifts. High-fat-high-fructose (H) diet, photoperiodic shifts induced chronodisruption (CD) and a combination (HCD) causes neurobehavioral perturbations wherein; the merits of exogenous melatonin in alleviating the said behavioral deficits are studied herein. Indices of anxiety (marble burying test, elevated plus maze test and hole board test) and depressive behavior (sucrose preference test, forced swim test and tail suspension test) were elevated in H, CD and HCD groups. Significant increments in the titres of thyroid hormone levels (T3, T4 and TSH) and mRNA levels of hippocampal pro-inflammatory genes (Tnf-, Il-1{beta}, Il-4, Il-6, Il-10, Il-12, Il-17, Mcp-1 and Nf-{kappa}b) in the said experimental groups corroborates with the said changes. Exogenous melatonin treatment to the said experimental groups viz. HM, CDM and HCDM; accounted for moderate to significant improvement in the said neurobehavioral perturbations and hippocampal inflammatory markers. Hippocampal BDNF-TrkB pathway genes of H, CD and HCD had recorded a non-significant downregulation in mRNA but without prominent changes in proteins. Likewise, melatonin-treated groups showed moderate to significant improvement in transcripts of Bdnf, Trkb, Nt-3, Nt-4, Psd-95 and Syn-1. Herein, we report neurobehavioral perturbations caused by a combination of H and CD. Melatonin-mediated improvement in neurobehavior and the corrective changes in hippocampal BDNF-TrkB pathway implies towards the potential anxiolytic and anti-depressive activity as reported herein.