Hasan, W. | Search bioRxiv

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↗

bioRxiv2025

Seizure-like behavior and hyperactivity in napb knockout zebrafish as a model for autism and epilepsy

We identified N-ethylmaleimide-sensitive factor attachment protein beta (NAPB) as a potential risk gene for autism and epilepsy. Notably, Qatari monozygotic triplets with loss of function mutations in NAPB exhibit early onset epileptic encephalopathy and varying degrees of autism. In this study, we generated NAPB zebrafish model using CRISPR-Cas9-sgRNAs technology for gene editing of the two orthologs napba and napbb. We observed that napb crispants (CR) show shorter motor neuron axons length together with altered locomotion behavior, including significant increases in larvae total distance traveled, swimming velocity, and rotation frequency, indicating that these behavioral changes effectively mimic the human epileptic phenotype. We applied microelectrode array (MEA) technology to monitor neural activity and hyperexcitability in the zebrafish model. The napb CR shows hyperexcitability in the brain region. By combining behavioral tests with electrophysiological MEA assays, the established NAPB zebrafish model can be employed to study the pathophysiological mechanisms of ASD and epilepsy to screen potential therapeutic drugs.

neuroscience↗