Biology subjects

Suryavanshi, S.

Publications and source records attributed to Suryavanshi, S..

3 recordsLinked to original sources

bioRxiv2026

Early-life stress-induced gut dysbiosis is ameliorated by nicotinamide treatment

Early life stress (ELS) in the form of adverse experiences in childhood results in multiple psycho-physiological pathologies during adulthood and accelerates aging. Such pathologies are recently observed to be alleviated upon nicotinamide treatment in a maternal separation model of ELS. We report a nicotinamide-driven amelioration of gut dysbiosis in middle-aged rodents with a history of neonatal maternal separation.

microbiology↗

bioRxiv2026

Allelic Variation at 9p21.3 Orchestrates Widespread RNA Splicing Shifts Governing Vascular Smooth Muscle Cell Plasticity

Genetic risk for coronary artery disease (CAD) has been linked to variants across more than 300 genomic loci. Whether and how these loci interface with RNA processing to drive disease-relevant cellular phenotypes remains unknown. Here, we applied haplotype-biased genome editing in induced pluripotent stem cells (iPSCs), followed by differentiation into vascular smooth muscle cells (VSMCs), to address how genetic variation at the strongest CAD locus - the 9p21.3 CAD risk locus - affects RNA processing and alternative splicing genome-wide. Using long-read RNA sequencing, we identified distinct allele-specific transcriptional programs driven by the two major haplotypes at 9p21.3, risk and non-risk. We unravel extensive reprogramming of mRNA splicing across the transcriptome, which leads to VSMC aberrant phenotypic modulation. The 9p21.3 risk haplotype disrupts transcript isoform expression and usage across multiple genomic loci implicated in diverse stages of atherosclerotic plaque development. We prioritized DDX5, previously implicated in CAD through GWAS. Isoform-specific modulation of DDX5 in VSMCs was sufficient to mitigate the 9p21.3 risk-associated molecular signature. Together, this work provides the first comprehensive isoform-level transcriptomic comparison of the two major haplotypes at the 9p21.3 locus and identifies a 9p21.3-DDX5 axis as a key regulator of VSMC phenotypic plasticity. These findings uncover allele-specific reprogramming of RNA splicing as a previously unrecognized mechanism underlying cardiovascular disease susceptibility and present a resource of targetable transcripts with potential relevance across vascular pathologies.

genetics↗

bioRxiv2020

Chronic chemogenetic activation of forebrain excitatory neurons in postnatal life evokes long-lasting changes in mood-related behavior

Early adversity is a key risk factor for the development of adult psychopathology, including anxiety, depression and schizophrenia. Rodent models of early adversity program persistent behavioral, molecular, metabolic, and neurophysiological changes. Perturbed signaling via forebrain Gq-coupled neurotransmitter receptors is a common feature across multiple models of early adversity. We addressed whether enhanced Gq-mediated signaling in forebrain excitatory neurons during postnatal life can evoke long-lasting mood-related behavioral changes. Excitatory hM3Dq DREADD-mediated chemogenetic activation of CamKII-positive forebrain excitatory neurons during postnatal life (P2-14) increased anxiety- and despair-like behavior, and evoked sensorimotor gating deficits in adulthood. In contrast, chronic chemogenetic hM3Dq DREADD activation of forebrain excitatory neurons in the juvenile or adult window did not evoke any mood-related behavioral alterations, highlighting the criticality of the postnatal temporal window. The enhanced anxiety-, despair- and schizophrenia-like behavioral changes evoked by chronic chemogenetic activation of forebrain excitatory neurons in postnatal life, was accompanied by an increased cortical and hippocampal metabolic rate of glutamatergic and GABAergic neurons in adulthood. Furthermore, animals with a history of postnatal hM3Dq activation exhibited a decline in the expression of activity-dependent and plasticity-associated markers within the hippocampus, along with perturbed hippocampal excitatory and inhibitory currents in adulthood. These results indicate that Gq signaling mediated activation of forebrain excitatory neurons during the critical postnatal window is sufficient to program altered mood-related behavior, as well as metabolic and neurophysiological changes in forebrain glutamate and GABA systems, recapitulating specific aspects of the consequences of early adversity.

neuroscience↗