Biology subjects

Devkar, R.

Publications and source records attributed to Devkar, R..

2 recordsLinked to original sources

bioRxiv2026

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

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.

animal behavior and cognition↗

bioRxiv2020

Alternative MyD88 -Cyclin D1 signaling in breast cancer cells regulates TLR3 mediated cell proliferation

TLR3 mediated apoptotic changes in cancer cells are well documented and hence several synthetic ligands of TLR3 are being used for adjuvant therapy. But there are reports showing contradictory effect of TLR3 signaling which includes our previous report that had shown cell proliferation following surface localization of TLR 3. However, the underlying mechanism of cell surface localization of TLR3 and subsequent cell proliferation lacks clarity. This study addresses TLR3 ligand mediated signaling cascade that regulates a proliferative effect in breast cancer cells (MDA MB 231 and T47D) challenged with TLR3 ligand in the presence of MyD88 inhibitor. Evidences were obtained using immunoblotting, co-immunoprecipitation, confocal microscopy, Immunocytochemistry, ELISA, and flowcytometry. Results had revealed that TLR3 ligand treatment significantly enhanced breast cancer cell proliferation marked by an upregulated expression of cyclinD1 but the same were suppressed by addition of MyD88 inhibitor. Also, expression of IRAK1-TRAF6-TAK1 were altered in the given TLR3-signaling pathway. Inhibition of MyD88 disrupted the downstream adaptor complex and mediated signaling through TLR3-MyD88-NF-{kappa}B (p65)-IL6-Cyclin D1 pathway. TLR3 mediated alternative signaling of the TLR3-MyD88-IRAK1-TRAF6-TAK1-TAB1-NF-{kappa}B axis leads to upregulation of IL6 and cyclinD1. This response is hypothesized to be via the MyD88 gateway that culminates in proliferation of breast cancer cells. Overall, this study provides first comprehensive evidence on involvement of canonical signaling of TLR3 using MyD88 - Cyclin D1 mediated breast cancer cell proliferation. The findings elucidated herein will provide valuable insights into understand the TLR3 mediated adjuvant therapy in cancer.

cancer biology↗