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Bhaskaran, A.

Publications and source records attributed to Bhaskaran, A..

3 recordsLinked to original sources

Exposure to perfluorooctanoic acid accelerates Drosophila melanogaster juvenile development and disrupts mitochondrial metabolism

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with poorly understood sublethal effects on insects. Perfluorooctanoic acid (PFOA), one of the most widely distributed legacy PFAS is increasingly recognized for altering organismal physiology beyond traditional toxicity endpoints. Here, we use the fruit fly Drosophila melanogaster as a model to examine how PFOA exposure during larval (juvenile) development reshapes insect life-history progression and metabolic homeostasis. Our studies reveal that at environmentally relevant concentrations (nM to low {micro}M), PFOA induces precocious expression of developmentally-regulated genes and leads to metabolic changes that persist into adulthood. At higher concentrations used to probe mechanism, PFOA accelerates larval development, disrupts mitochondrial membrane potential, and increases whole-organism metabolic heat production - results that suggest altered mitochondrial energetic efficiency. Consistent with this tradeoff, PFOA-exposed larvae that develop faster under permissive conditions exhibit heightened sensitivity to environmental stressors, including elevated temperature and reduced food hydration. Together, these findings demonstrate that PFOA disrupts metabolic and developmental processes in a dose- and context-dependent manner, highlighting sublethal effects that may influence insect resilience under environmental stress. SYNOPSIS STATEMENTHere we describe how PFOA alters the growth, development, and metabolism of the fruit fly Drosophila melanogaster. Specifically, we find that PFOA accelerates Drosophila juvenile growth while also rendering exposed larvae sensitive to environmental stress. These observations suggest that widespread PFOA contamination may impair the developmental fitness of insect populations.

pharmacology and toxicology↗

High-resolution quantification of metabolic heat output from individual live Drosophila brains

Quantitative insights into brain metabolism are essential for advancing our understanding of energy dynamics in the brain. However, current approaches for tracking brain metabolism, metabolic profiling and respirometry, provide only static snapshots of metabolite levels or lack the required resolution. Here, we develop a novel nanowatt-resolution biocalorimeter capable of real-time continuous measurements of heat output to quantitatively measure the metabolism of individual live Drosophila melanogaster brains and investigate how sex, genotype, age, and disease affect brain metabolism. We show for the first time that female brains, across multiple wild-type genotypes, exhibit a significantly higher metabolic rate ([~]10%) than male brains at a young age (<10 days old) and follow distinct metabolic trajectories across the lifespan. We also find that parkin mutants, a genetic model for Parkinsons disease, exhibit a [~]15% reduction in brain metabolic output relative to controls, revealing that defective mitophagy due to parkin deficiency affects brain metabolism. Furthermore, we measure the metabolic rate of reproductive tissues of Drosophila, highlighting the broad applicability of our biocalorimeter. Together, these advances open new avenues for investigating how tissue-specific metabolism is impacted by aging, neurodegeneration, and disease states. TeaserDirect measurement of metabolic rate of individual Drosophila brains to investigate how sex, genotype, age, and disease affect brain metabolism.

bioengineering↗

Fluoxetine treatment during postnatal and juvenile temporal epochs evokes diametrically opposing changes in anxio-depressive behaviors, gene expression, mitochondrial function, and neuronal architecture in the medial prefrontal cortex

BackgroundThe selective serotonin reuptake inhibitor, fluoxetine is reported to evoke distinct effects on anxio-depressive behaviors based on the temporal window of administration. Here, we systematically addressed the influence of postnatal or juvenile fluoxetine treatment on anxio-depressive behavior, gene expression, mitochondrial biogenesis, and neuronal cytoarchitecture in adulthood. MethodsRat pups received postnatal fluoxetine (PNFlx) or juvenile fluoxetine (JFlx) treatment from postnatal day 2 (P2)-P21 or P28-48 respectively, and were assessed for changes in anxio-depressive behaviors, global gene expression, mitochondrial biogenesis/function, and dendritic cytoarchitecture in the medial prefrontal cortex (mPFC) in adulthood. ResultsPNFlx evoked long-lasting increases in anxio-depressive behaviors, whereas JFlx elicited persistent decreases in anxio-depressive behavior, accompanied by differential and minimally overlapping transcriptional changes in the mPFC in adulthood. We noted opposing changes in mitochondrial function and dendritic cytoarchitecture in the mPFC of PNFlx and JFlx animals, with a decline observed following PNFlx and an increase in response to JFlx treatment. Furthermore, the enhanced despair-like behavior in the PNFlx cohort was reversed by adult-onset treatment with nicotinamide, a precursor for NAD+ which enhances mitochondrial bioenergetics. ConclusionsFluoxetine treatment in early postnatal versus juvenile windows evokes opposing and persistent effects on anxio-depressive behavior in adult male rats, along with differential effects on gene expression, mitochondrial function, and dendritic morphology in the mPFC. Collectively, our findings highlight two distinct temporal windows in which fluoxetine exposure programs starkly differing outcomes in mood-related behavior, and posits a role for altered bioenergetics within the mPFC in contributing to these distinctive changes in emotionality.

neuroscience↗