Biology subjects

Selvaraji, S.

Publications and source records attributed to Selvaraji, S..

7 recordsLinked to original sources

bioRxiv2026

Modelling prodromal Parkinson's disease- gastrointestinal pathology and early motor deficits in mice after transient rotenone exposure

Early gastrointestinal (GI) dysfunction is a hallmark feature of Parkinson's disease (PD), yet models capturing prodromal gut and brain pathology in PD remain limited. Motivated by the increased PD risk associated with pesticide exposure, we monitored motor behavior, brain pathology, and GI structure and function over 9 months following 5 daily doses of rotenone in mice. Transient rotenone exposure induced significant nigrostriatal pathology, including {approx}48% loss of dopaminergic neurons and increased -synuclein aggregation in the substantia nigra, without significant changes in gross motor function. Notably, we identified pronounced GI dysfunction including reduced colonic transit velocity, altered motility dynamics, and delayed whole-gut transit. These functional changes were accompanied by enteric dopaminergic neurodegeneration, increased colonic -synuclein accumulation, increased colonic crypt depth, goblet cell hyperplasia with elevated mucin content per goblet cell. The findings are consistent with prodromal PD, suggesting the utility of this model for investigating early disease mechanisms and intervention strategies.

neuroscience↗

bioRxiv2025

Magnetoelectric nanodiscs diminish motor deficits in a model of Parkinson's disease

Magnetoelectric nanodiscs (MENDs) offer a wireless, minimally invasive route to neuromodulation by converting weak magnetic fields into electric polarization, but their therapeutic applications have remained unrealized. Here, we report the therapeutic development of MENDs for deep brain stimulation (DBS) in the subthalamic nucleus (STN) to alleviate motor deficits in a mouse model of Parkinsons disease. To quantitatively assess therapeutic outcomes, we introduce GaitPattern, a computational pipeline that extracts DBS-induced alterations in salient gait features. Using GaitPattern, we demonstrate that MEND-mediated STN DBS induces motor improvements with precision comparable to clinical electrode-based DBS, while minimizing inflammatory responses associated with the implanted hardware. Notably, MEND-mediated DBS reduces oxidative stress in the brain, a key contributor to neurodegeneration. These findings position MEND-mediated STN DBS as an effective and minimally invasive neuromodulation strategy.

neuroscience↗

bioRxiv2024

Impact of Parental Time-Restricted Feeding on Offspring Metabolic Phenotypic Traits

A substantial body of research elucidates the mechanisms and health advantages associated with intermittent fasting (IF). However, the impact of parental IF on offspring remains unclear. Through an investigation involving four IF and ad libitum combinations of parental mating groups, we demonstrate that parental IF (daily time-restricted feeding) influences offsprings metabolic health indicators in male and female offspring in distinct ways. We found that when both parents are on IF their offspring exhibit protection against the adverse effects of a high-fat, high-sugar, and high-salt diet in a sex-specific manner. This study underscores the potential significance of parental lifestyle modifications involving dietary restriction for the metabolic status of their children and their risk for obesity and diabetes.

genetics↗

bioRxiv2023

FUNCTIONAL AGEING: A Science-Technology-Society Approach to teach Ageing and Age-related Diseases

PurposeAgeing is a complex biological process that involves numerous genes and pathways. Experimental studies have identified several of these genes and pathways that that can extend or shorten an individuals lifespan. Understanding these genes and pathways can help develop interventions that improve health and quality of life of older people. Nonetheless, as the global population continues to age, it is essential to comprehend the ageing processs impact on society. Functional age is defined as a combination of chronological, biological, and psychological ages. An educational course called "Functional Ageing" was created for life science students at the National University of Singapore (NUS) during the academic year 2016-2017. The module adopted an interdisciplinary approach based on science-technology-society (STS) methodology and aimed to equip students with the analytical tools needed to assess the ageing process at both the molecular and physiological/functional levels. Ultimately, the module aimed to promote the understanding of ageing processes, particularly functional ageing in a population and its societal impacts. MethodsThis "Functional Ageing" course spanned over 13 weeks, consisting of weekly four-hour sessions that aimed to integrate both biology of ageing and societal perceptions of an ageing population. The first half of the semester covered the molecular processes that govern ageing, while the second half focussed on societal perception, burden of disease, healthy ageing interventions and creating an ageless society. Experimental and epidemiological studies were used to explain the ageing process. Expert guest lecturers were invited throughout the module to share their experiences on the demanding research areas of ageing today, as well as clinical aspects of age-related diseases. In addition, a field visit to a geriatric ward at the mental health organisation was arranged to showcase the countrys approach to dealing with the rising demands of ageing, and to provide experiential learning that can help inculcate a clearer public perception of ageing. ResultsThis 13-week module helped to improve students perception about functional ageing in todays society. After the module, a reflection analysis was conducted to evaluate students perceptions of ageing society. Overall findings garnered have demonstrated that while students generally have a brief understanding of the biological processes of ageing, their perception on how ageing is being manifested in a public health and societal setting is in paucity. However, the routine university-directed feedback survey indicated that the module had a positive impact on students appreciation and comprehension of the interplay between biological and sociological aspects of ageing, thus achieving the learning objectives of the module. ConclusionThe aim of the "Functional ageing" module was to integrate the biology and sociology of ageing to provide a better interdisciplinary understanding of ageing in society. After completing the module, students demonstrated a change in their mindset and attitude towards how their scientific understanding of ageing can be coupled to their public perception of ageing. As ageing populations become more prevalent in many societies, it is crucial that we prepare for an ageing population and develop a positive perception of ageing. Through educational efforts like this course/module, students will exhibit greater awareness of ageing issues, leading to more informed and balanced perceptions.

scientific communication and education↗

bioRxiv2021

Multiomics Analyses Reveal Dynamic Bioenergetic Pathways and Functional Remodeling of the Heart During Intermittent Fasting

AimsIntermittent fasting (IF) reduces cardiovascular risk factors in animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction, but the underlying molecular mechanisms are unknown. To delineate molecular and cellular adaptations of the heart to IF, we carried out system-wide comprehensive analyses of proteome and phosphoproteome, complemented with transcriptome profiling, followed by functional analysis. Methods and resultsIn order to understand molecular and cellular remodeling of the heart during IF, we employed advanced mass spectrometry for system-wide profiling of the proteome and phosphoproteome of heart tissues obtained from mice maintained for 6 months on either daily 12- or 16-hour fasting, every-other-day fasting or ad libitum control feeding regimens. We also performed transcriptome analyses using RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. IF regimens significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Comparison of differentially expressed proteome and transcriptome upon IF showed the higher correlation of pathway alternation in short IF regimen but the inverse correlation of metabolic processes such as fatty acid oxidation and immune processes in longer IF regimens. In addition, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance. ConclusionOur systematic multi-omics study elucidates a molecular framework for understanding how IF impacts the hearts function and its vulnerability to injury and disease. Translational perspectiveIntermittent fasting is emerging as a desirable lifestyle adaptation to impact cardiovascular health through the modulation of molecular and cellular mechanisms, and by acting on disease risk factors. Evidence from numerous studies indicates that the fasting cycles are highly and consistently effective in protecting against cardiovascular diseases and improving cardiac health in animals and human. Using multi-omics, here we dissect distinct molecular adaptations of the heart to different intermittent fasting regimens. Our results unveil novel cardioprotective mechanisms and open up new avenues for innovative pharmacological approaches to prevent and treat cardiovascular diseases.

systems biology↗

bioRxiv2020

Hippocampal Transcriptome Profiling Reveals Common Disease Pathways in Chronic Hypoperfusion and Ageing

Vascular dementia (VaD) is a progressive cognitive impairment of vascular etiology. VaD is characterized by cerebral hypoperfusion, increased blood-brain barrier permeability and white matter lesions. An increased burden of VaD is expected due to rapidly aging populations. The hippocampus is particularly susceptible to hypoperfusion, and the resulting memory impairment may play a crucial role in VaD. Here we have investigated the hippocampal gene expression profile of young and old mice subjected to chronic cerebral hypoperfusion by bilateral common carotid artery stenosis (BCAS). Our data in sham-operated young and aged mice show the normal age-associated decline in cerebral blood flow and differential gene expression. BCAS and ageing caused broadly similar effects, however, BCAS-induced changes in hippocampal gene expression differed between young and aged mice. Specifically, transcriptomic analysis indicated that in comparison to young sham mice, many pathways altered by BCAS in young mice resembled those present in sham aged mice. Immunoblot analyses confirmed these findings. Finally, relative to young sham mice the cell type-specific profile of genes in both young BCAS and old sham animals further revealed common cell-specific genes. Our data provide a genetic-based molecular framework for chronic hypoperfusion-induced hippocampal damage and reveal common cellular signaling pathways likely to be important in the pathophysiology of VaD.

neuroscience↗

bioRxiv2020

AIM2 Inflammasome Mediates Hallmark Neuropathological Alterations and Cognitive Impairment in a Mouse Model of Vascular Dementia

Chronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long-term cognitive impairment and memory loss. Here we used a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate its effect on the innate immune response - particularly the inflammasome signaling pathway. Comprehensive analyses revealed that chronic cerebral hypoperfusion induces a complex temporal expression and activation of inflammasome components and their downstream products (IL-1{beta} and IL-18) in different brain regions, and promotes activation of apoptotic and pyroptotic cell death pathways. Polarized glial cell activation, white matter lesion formation and hippocampal neuronal loss also occurred in a spatiotemporal manner. Moreover, in AIM2 knockout mice we observed attenuated inflammasome-mediated production of proinflammatory cytokines, apoptosis and pyroptosis, as well as resistance to chronic microglial activation, myelin breakdown, hippocampal neuronal loss, and behavioural and cognitive deficits following BCAS. Hence, we have demonstrated that activation of the AIM2 inflammasome substantially contributes to the pathophysiology of chronic cerebral hypoperfusion-induced brain injury and may therefore represent a promising therapeutic target for attenuating cognitive impairment in VaD.

neuroscience↗