Biology subjects

Mehta, K.

Publications and source records attributed to Mehta, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Primary Human Macrophages Exhibit Functional CYP3A4 Activity with Marked Expression-Function Discordance and Cocaine-Induced Catalytic Activation

CYP3A4 is a phase I drug-metabolizing enzyme responsible for transformation of ~50% of clinically relevant drugs. While extensively characterized in hepatocytes, its role in immune cells remains poorly understood. Here, using primary human monocyte-derived macrophages, we identify an understudied extrahepatic site of CYP3A4-mediated drug metabolism. Macrophages from 100 independent donors expressed CYP3A4 and its transcriptional regulators, Pregnane X Receptor (PXR) and Constitutive Androstane Receptor (CAR), with substantial interindividual variability. Importantly, CYP3A4 protein expression was accompanied by measurable catalytic activity in intact macrophages, yet CYP3A4 mRNA, protein abundance, and activity lacked concordance, demonstrating that expression alone may not predict function. In vivo, CYP3A4 was expressed in rhesus macaque Kupffer cells, further supporting macrophages as a potential pharmacologic entity. We next evaluated cocaine as a potential modulator of CYP3A4, due to its role in xenobiotic clearance. Cocaine had a dichotomous effect on expression, increasing CYP3A4 in some donors while producing no change or decreases in others, a phenotype associated with PXR, CAR, and the sigma-1 cocaine receptor. Strikingly, despite these divergent expression responses, cocaine increased CYP3A4 catalytic activity in all donors, reaching or exceeding levels induced by rifampicin, a clinically relevant CYP3A4 inducer. In rhesus macaques, cocaine also decreased antiretroviral therapy tissue concentrations, coincident with increased CYP3A4 and PXR. Together, these findings establish macrophages as a functionally active extrahepatic site of CYP3A4 metabolism and reveal a critical disconnect between CYP3A4 expression and catalytic function. Moreover, our findings identify interindividual variability and expression-activity discordance as important considerations for personalized medicine and understanding clinically relevant drug-drug interactions in the context of substance use.

pharmacology and toxicology↗

bioRxiv2026

Wavelet Transform improves time-frequency characterization of the Electroretinographic Oscillatory Potentials as compared to Short-Time Fourier Transform across experimental and clinical models

Purpose: To compare continuous wavelet transform (CWT) and short-time Fourier transform (STFT) analyses of the oscillatory potentials (OPs) of the dark-adapted full-field electroretinogram (FFERG). Methods: FFERG recordings from Royal College of Surgeons (RCS) and healthy Brown Norway (BN) rats, wild-type and Atoh7 enhancer-knockout (KO) mice, and patients with diabetic retinopathy and healthy controls were analyzed with STFT and with CWT employing the real Morlet wavelet, after 60 Hz high-pass and sharp 60 Hz notch filtering. Time- and frequency-localized OP features were quantified and the methods compared on detection of transient OP signals. Both were additionally validated using synthetic OP-like bursts of known frequency embedded in each cohort's recorded noise. Results: CWT revealed distinct time-frequency patterns and disease-specific OP alterations across all rat, mouse, and human cohorts, with improved temporal localization and frequency resolution, whereas STFT merged transient features and was more susceptible to noise. CWT-derived dominant-frequency differences reached significance in all three models; the corresponding STFT difference reached significance only in rats (separate tests; methods not directly compared). In synthetic bursts, both methods recovered injected frequencies to within 1-2.5 Hz, but only CWT resolved two bursts separated by 15 ms. Conclusions: CWT employing the real Morlet wavelet provides a robust, physiologically relevant evaluation of OPs, with improved temporal localization and reduced spectral dispersion relative to STFT in clinical and experimental settings. Translational Relevance: CWT analysis may improve the characterization of inner retinal dysfunction by preserving transient OP time-frequency structure, as illustrated in preclinical rodent models and diabetic retinopathy patients.

physiology↗

bioRxiv2026

Highly replicable multisite patterns of adolescent white matter maturation

The Adolescent Brain Cognitive Development (ABCD) Study is the largest U.S.-based neuroimaging initiative of adolescent brain maturation. Diffusion MRI (dMRI) provides unique insights into white matter organization, yet applying advanced processing pipelines and managing technical variability across scanning environments remains challenging at scale. To address these issues, we present ABCD-BIDS Community Collection (ABCC) release 3.1.0, including a curated resource of more than 24,000 fully processed ABCD dMRI datasets. ABCC provides fully processed images, nuanced image quality metrics, advanced microstructural measures, and person-specific bundle tractography. Evaluating these rich data revealed that measures of diffusion restriction and non-Gaussianity--in particular the intracellular volume fraction from NODDI and return-to-origin probability from MAP-MRI--were highly sensitive to neurodevelopment and robust to variation in image quality. Additionally, harmonization of microstructural features markedly improved the cross-vendor generalizability of developmental effects. Together, ABCC accelerates reproducible, rigorous research on adolescent white matter development.

neuroscience↗

bioRxiv2026

Enhanced strand transfer and mismatch extension by HIV-1C reverse transcriptase promote sequence motif duplication

Genetic diversification of HIV-1 is driven largely by the error-prone activity of reverse transcriptase (RT) and frequent template switching during reverse transcription. A rare outcome of nonhomologous recombination is sequence motif duplication, which can alter viral gene regulation and protein function. Previous studies have shown that such duplications occur at significantly higher frequencies in HIV-1 subtype C (HIV-1C), particularly within the long terminal repeat (LTR) and p6-Gag regions, where they can confer replication advantages. However, the mechanistic basis for this subtype-specific bias remains unclear. We therefore investigated whether intrinsic biochemical properties of HIV-1C RT contribute to its elevated duplication frequency. Bioinformatic analysis of 6,877 full-length HIV-1 genomes identified four duplication hotspots, with the highest frequencies in HIV-1C. Comparative sequence analysis of RT revealed several subtype-specific residues, including a highly conserved threonine at position 359 (T359) in the connection domain of HIV-1C RT. Structural modeling suggested that T359 can form an additional hydrogen bond with the nascent cDNA, potentially stabilizing the RT-template complex. Biochemical characterization of recombinant RT variants demonstrated that residue 359 modulates polymerase activity and maintains subtype-specific optimal catalytic function. Functional assays further revealed that HIV-1C RT exhibits enhanced template strand transfer compared with HIV-1B RT. In addition, next-generation sequencing-based primer extension assays showed that HIV-1C RT extends mismatched 3' termini more efficiently across multiple mismatch types. Together, these findings indicate that subtype-specific biochemical properties of HIV-1C RT, particularly enhanced strand transfer and mismatch extension mediated in part by T359, promote nonhomologous recombination events that generate sequence motif duplications. This work provides a mechanistic explanation for the elevated duplication frequency characteristic of HIV-1C and highlights how subtle RT polymorphisms can shape viral evolutionary trajectories.

microbiology↗

bioRxiv2025

An Open, Fully-processed, Longitudinal Data Resource to Study Brain Development and Transdiagnostic Executive Function

Executive function (EF) develops rapidly during adolescence. However, deficits in EF also emerge in adolescence, representing a transdiagnostic symptom associated with many forms of psychopathology. To promote transdiagnostic research on EF during development, we introduce a new data resource - the Penn Longitudinal Executive functioning in Adolescent Development study (Penn LEAD) - that combines longitudinal multimodal imaging data with rich clinical and cognitive phenotyping. These data include 225 imaging sessions from 132 individuals (8-16 years old at the time of enrollment) who are typically developing (27.3%), or meet criteria for attention-deficit hyperactivity disorder (20.5%) or the psychosis-spectrum (52.3%). In addition to phenotypic data from multiple cognitive tasks focused on EF, the study includes data from structural MRI, diffusion MRI, n-back task fMRI, resting-state fMRI, and arterial spin-labeled MRI. Notably, all raw data, fully-processed derived data, and detailed quality control recommendations are publicly shared on OpenNeuro. We anticipate that such analysis-ready data will accelerate research on EF development in psychiatry.

neuroscience↗

bioRxiv2025

Antiviral and Anti-inflammatory Effects of Cannabidiol in HIV/SIV Infection

Persistent reservoirs and chronic immune activation are hallmarks of HIV, despite the effectiveness of antiretroviral therapy (ART) in suppressing viral replication. Here, we use rhesus macaques and primary and induced pluripotent stem cell (iPSC)-derived human immune cells to evaluate the virologic and immunologic consequences of cannabidiol (CBD) exposure during HIV/SIV infection. We show that CBD, in the absence of ART, suppresses viral replication and establishment of the viral reservoir to levels comparable with first-line therapies during acute SIV infection of rhesus macaques. This antiviral effect of CBD extended to in vitro HIV infection of human macrophages, T cells, and microglia. Immunologically, we observe CBD slowed CD4+ T cell decline and polarization, decreased CD14+CD16+ monocyte expansion, and reduced interferon-inducible cytokine release in rhesus macaques. We identify comparable effects on cytokine production with in vitro CBD treatment of human macrophages, T cells, and microglia. Importantly, we find CBD inhibits cytokines only when an immune response is elicited by HIV, suggesting it is not broadly immunosuppressive. Finally, we determine CBD regulates endocannabinoid receptors, modulators, and transporters and inhibits NF-{kappa}b and STAT1 activation when mediating its antiviral and anti-inflammatory effects. These findings show beneficial effects of CBD in laboratory models of untreated HIV, thus placebo-controlled clinical trials to evaluate the safety and effectiveness of adjunctive CBD use with ART is warranted.

microbiology↗

bioRxiv2025

Uncovering asparagine utilization pathway, a critical requirement for mycobacterial pH-driven adaptation at the host-pathogen crossroads

M. tuberculosis, an intracellular pathogen, thrives in a specialized membrane-bound vacuole, the phagosome with acidic pH and limited access to nutrients. To survive and replicate within human host, M. tuberculosis must adapt and fulfil its nutritional requirements. To understand how the bacillus captures nutrients from its host, we studied mycobacterial acquisition of host-derived amino acids, the preferred nitrogen sources. We discovered that PhoP, a key determinant of mycobacterial adaptation to phagosomal acidification, controls expression of AnsP1 and AnsP2 to facilitate acquisition of host aspartate and asparagine, respectively. Thus, macrophage-infected WT-H37Rv showed a significantly higher level of intra-bacterial Asn compared to the phoP-KO mutant and a complemented mutant could restore Asn level to that of WT-H37Rv. Under acidic conditions, elevated DNA binding of PhoP within the promoters lead to direct activation of ansP1 and ansP2. Consistently, phoP-KO is unable to utilize Asn under acidic condition, and over-expression of ansP1 or ansP2 restored intracellular growth defect of the mutant. These findings uncover the regulatory network allowing utilization of organic nitrogen sources by the pathogen during infection. Author summaryHuman Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a global public health burden claiming [~]1.25 million deaths in 2023. To investigate how the bacillus captures nitrogen sources from its host, we studied acquisition of host amino acids aspartate (Asp) and asparagine (Asn) by the tubercle bacilli. We show that PhoP, a key determinant of mycobacterial adaptation to phagosomal acidification, controls expression of Asp and Asn transporters to facilitate acquisition of host amino acids by the pathogen. A mutant lacking phoP is unable to utilize Asn under acidic conditions, whereas over-expression of ansP1 and/or ansP2 restored growth defect of the phoP-KO in vitro and in macrophages. Together, these findings uncover the transcriptional landscape allowing utilization of organic nitrogen sources by the tubercle bacilli during infection.

microbiology↗

bioRxiv2025

Group handling using Mus-Bus, a cage-transfer cum enrichment device reduces stress, anxiety and time taken for cage changes and enhances voluntary interaction in C57BL/6NCrl mice

It has been proven that tail-lifting mice can cause stress, anxiety and aversive behavior, and this finding has made scientists develop less stressful techniques like cupping and tunnel-handling. All these techniques have a disadvantage in that they can only handle mice individually and not in groups. This study produces scientific evidence on the advantages of group handling of laboratory mice for the first time. Group handling using the novel device significantly reduced the time taken and number of attempts taken for cage changes, a major reason that prevented tunnel-handling from being adopted globally. Shifting mice in groups using a device named "Mus-Mobile" resulted in significantly lower fecal corticosteroid levels, higher voluntary interaction time and the open field activity and time spent in the central arena were not altered when compared with tail lifting and tunnel handling in C57BL/6NCrl mice. Body weights were not different when Mus-Mobile was employed with respect to the other groups. This work shows that group-shifting is the next horizon for animal welfare, as this device can revolutionize the handling of laboratory mice to bring in better animal wellbeing.

animal behavior and cognition↗

bioRxiv2025

An open, fully-processed data resource for studying mood and sleep variability in the developing brain

Brain development during adolescence and early adulthood coincides with shifts in emotion regulation and sleep. Despite this, few existing datasets simultaneously characterize affective dynamics, sleep variation, and multimodal measures of brain development. Here, we describe the study protocol and initial release (n = 10) of an open data resource of neuroimaging paired with densely sampled behavioral measures in adolescents and young adults. All participants complete multi-echo functional MRI, compressed-sensing diffusion MRI, and advanced arterial spin-labeled MRI. Behavioral measures include ecological momentary assessment, actigraphy, extensive cognitive assessments, and detailed clinical phenotyping focused on emotion regulation. Raw and processed data are openly available without a data use agreement and will be regularly updated as accrual continues. Together, this resource will accelerate research on the links between mood, sleep, and brain development.

neuroscience↗

bioRxiv2025

Reproducible Brain Charts: An open data resource for mapping brain development and its associations with mental health

Major mental disorders are increasingly understood as disorders of brain development. Large and heterogeneous samples are required to define generalizable links between brain development and psychopathology. To this end, we introduce the Reproducible Brain Charts (RBC), an open data resource that integrates data from 5 large studies of brain development in youth from three continents (N=6,346; 45% Female). Confirmatory bifactor models were used to create harmonized psychiatric phenotypes that capture major dimensions of psychopathology. Following rigorous quality assurance, neuroimaging data were carefully curated and processed using consistent pipelines in a reproducible manner with DataLad, the Configurable Pipeline for the Analysis of Connectomes (C-PAC), and FreeSurfer. Initial analyses of RBC data emphasize the benefit of careful quality assurance and data harmonization in delineating developmental effects and associations with psychopathology. Critically, all RBC data - including harmonized psychiatric phenotypes, unprocessed images, and fully processed imaging derivatives - are openly shared without a data use agreement via the International Neuroimaging Data-sharing Initiative. Together, RBC facilitates large-scale, reproducible, and generalizable research in developmental and psychiatric neuroscience.

neuroscience↗

bioRxiv2025

A repressor co-regulatory network integrates iron acquisition to mycobacterial stress tolerance

Growing evidence suggests that controlled regulation of iron (Fe) uptake is essential for mycobacterial survival and proliferation in the host. In this study, we discovered the mechanism that links mycobacterial Fe acquisition to intra-bacterial redox environment via the phoP locus. Remarkably, regulated expression of the major Fe storage protein encoding gene bfrB determines bacterial tolerance to oxidative stress and intracellular survival of the pathogen. Transcriptomic analysis coupled with in vivo DNA binding studies uncover a distinct IdeR-independent regulation, which utilizes Lsr2 and virulence regulator PhoP to modulate transcriptional control of bfrB via recruitment of both the regulators. A striking inhibition of Lsr2 binding to the bfrB promoter in a phoP-KO mutant, attributable to Lsr2-PhoP protein-protein interaction, provides the most fundamental biological insight. Building on these results, we proposed a model suggesting how Lsr2-PhoP interaction (or lack thereof) contributes to repression and/or stress-specific activation of bfrB expression. Collectively, these results uncover a key mechanism linking Fe acquisition and oxidative stress response of mycobacteria, and have significant implications on the intracellular survival of the pathogen.

microbiology↗

bioRxiv2025

Developmental Variations in Recurrent Spatiotemporal Brain Propagations from Childhood to Adulthood

The brain undergoes profound structural and functional transformations from childhood to adolescence. Convergent evidence suggests that neurodevelopment proceeds in a hierarchical manner, characterized by heterogeneous maturation patterns across brain regions and networks. However, the maturation of the intrinsic spatiotemporal propagations of brain activity remains largely unexplored. This study aims to bridge this gap by delineating spatiotemporal propagations from childhood to early adulthood. By leveraging a recently developed approach that captures time-lag dynamic propagations, we characterized intrinsic dynamic propagations along three axes: sensory-association (S-A), task-positive to default networks (TP-D), and somatomotor-visual (SM-V) networks, which progress towards adult-like brain dynamics from childhood to early adulthood. Importantly, we demonstrated that as participants mature, there is a prolonged occurrence of the S-A and TP-D propagation states, indicating that they spend more time in these states. Conversely, the prevalence of SM-V propagation states declines during development. Notably, top-down propagations along the S-A axis exhibited an age-dependent increase in occurrence, serving as a superior predictor of cognitive scores compared to bottom-up S-A propagation. These findings were replicated across two independent cohorts (N = 677 in total), emphasizing the robustness and generalizability of these findings. Our results provide new insights into the emergence of adult-like functional dynamics during youth and their role in supporting cognition.

neuroscience↗

bioRxiv2024

Transcriptomic profiling of healthy individual-derived LCLs revealed inter-individual variability towards-hypoxia-responsive pathways

Hypoxia, or low oxygen levels, affects various developmental, physiological, and pathological processes. Its been consistently reported that there is an inter-individual variability at genetic and molecular pathways related to oxygen sensing and response. Understanding the underlying variability towards hypoxia sensing and response in health and disease conditions is challenging. The Prakriti stratification method of Ayurveda offers solutions, which classifies healthy individuals into different groups based on multisystem phenotyping. Our lab has previously used this method and provided evidence for the variability in hypoxia responsiveness physiologically among healthy individuals at population levels. Our current study seeks to understand hypoxia sensing and response pathways at cellular levels. We used eight Lymphoblastoid cell lines (LCLs) developed from healthy individuals of extreme Prakriti types. Hypoxia challenge experiments were performed using 0.2% oxygen for 24 and 48 hrs. of chronic hypoxia and captured global transcriptomics profiles. Differentially expressed genes revealed activation of core hypoxia-induced transcriptomic signatures, such as HIF-1 signaling and their metabolic reprogramming in pooled as well as in all Prakriti groups. However, there were Prakriti-specific differences, such as activation of TGF-{beta} mediated ROS and PI3K/AKT/mTOR driven mTORC1 complex in Kapha, downregulation of cholesterol homeostasis and regulation of Phosphoinositide biosynthesis in membrane potential observed in the Pitta group. In contrast, ER stress-induced activation of cell survival response via Unfolded protein response in the Vata group. The Prakriti stratification method will provide a novel method to understand inter-individual differences in hypoxia response pathways. SignificanceHypoxia can significantly impact various aspects of our health and well-being. All nucleated cells sense and respond to hypoxia, depending upon their cellular and metabolic activities. Its wide utility and spatiotemporal regulation make it a crucial target to study. We have used the Prakriti stratification method of Ayurveda to explore hypoxia sensing and response at cellular levels. Lymphoblastoid Cell Lines (LCLs) developed from the peripheral blood of stratified healthy individuals have been utilized to study the expression level variability at the baseline and hypoxia-induced conditions. The outcomes of our study will be crucial to understanding inter-individual variability in response to hypoxia overlayed baseline variations. Resulting in differential susceptibility towards hypoxic response in health and contributes to understanding variable outcomes in disease conditions. Molecular targets from our study will further be utilized for interventional drug targets in hypoxia-induced disease conditions.

cell biology↗

bioRxiv2024

Exploring Comorbidity Networks in Mild Traumatic Brain Injury Subjects through Graph Theory: A Traumatic Brain Injury Model Systems Study

Traumatic brain injuries (TBIs) are characterized by myriad comorbidities that affect the functioning of the affected individuals. The comorbidities that TBI subjects experience span a wide range, ranging from psychiatric diseases to those that affect the various systems of the body. This is compounded by the fact that the problems that TBI subjects face could span over an extended period post-primary injury. Further, no drug exists to prevent the spread of secondary injuries after a primary impact. In this study, we employed graph theory to understand the patterns of comorbidities after mild TBIs. Upon application of network analysis and a novel clustering algorithm, we discovered interesting associations between comorbidities in young and old subjects with the condition. Specifically, bipolar disorder was seen as related to cardiovascular comorbidities, a pattern that was observed only in the young subjects. Similar associations between obsessive-compulsive disorder and rheumatoid arthritis were observed in young subjects. Psychiatric comorbidities exhibited differential associations with non-psychiatric comorbidities depending on the age of the cohort. The study results might have implications for effective surveillance and the management of comorbidities post mild TBIs.

neuroscience↗

bioRxiv2024

A sensorimotor-association axis of thalamocortical connection development

Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence1-6. The brains capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity7-12, here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth. We first introduce, cortically annotate, and anatomically validate a new atlas of human thalamocortical connections using diffusion tractography. By applying this atlas to three independent youth datasets (ages 8-23 years; total N = 2,676), we reproducibly demonstrate that thalamocortical connections develop along a maturational gradient that aligns with the cortexs sensorimotor-association axis. Associative cortical regions with thalamic connections that take longest to mature exhibit protracted expression of neurochemical, structural, and functional markers indicative of higher circuit plasticity as well as heightened environmental sensitivity. This work highlights a central role for the thalamus in the orchestration of hierarchically organized and environmentally sensitive windows of cortical developmental malleability.

neuroscience↗

bioRxiv2024

Context-dependent acetylation of the virulence regulator PhoP accounts for carbon-source specific mycobacterial growth inhibition under acidic conditions

Mycobacterium tuberculosis PhoP is essential for intracellular survival and virulence of the tubercle bacilli. Genetic evidences coupled with biochemical studies uncover that PhoP affects various aspects of M. tuberculosis pathophysiology including pH sensing during intracellular adaptation and carbon source utilization. Building on this observation, herein we report essentiality of the phoP locus in carbon-source specific mycobacterial growth. Further, our results on mycobacterial growth in the presence of different carbon sources suggest accumulation of acetyl CoA, a metabolic intermediate which acetylates major transcription factors. To explore the mechanism, we examined in vivo acetylation of PhoP, and our results suggest a link between acetylation of PhoP and mycobacterial carbon source utilization. Using a genetic screening, we identified PhoP-specific mycobacterial acetylases. Our two major findings that (a) acidic conditions of growth inhibit PhoP acetylation, which represses PhoP regulon by interfering with DNA binding activity of the regulator and (b) mycobacteria expressing acetylation-defective PhoP shows growth inhibition, together suggest a role of acetylation on mycobacterial growth via carbon-source utilization. These results have implications on intracellular survival and growth program of mycobacteria under varying environmental cues.

microbiology↗

bioRxiv2023

Phosphatidylinositol 3-phosphate mediates Arc capsids secretion through the multivesicular body pathway

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) is an immediate early gene that plays a vital role in learning and memory. The recent discovery that Arc mediates the inter-neuronal RNA transfer implies its role in regulating neuronal functions across long distances. Arc protein has structural and functional properties similar to viral Group-specific antigen (Gag). By assembling into high-order, virus-like capsids, Arc mediates the intercellular RNA transfer. However, the exact secretion pathway through which Arc capsids maneuver cargos is unclear. Here, we identified that Arc capsids assemble and secrete through the endosomal-multivesicular body (MVB) pathway. Arcs endosomal entry is likely mediated by phosphatidylinositol-3-phosphate (PI3P). Indeed, reconstituted Arc protein preferably binds to PI3P. In mammalian cells, Arc forms puncta that colocalizes with FYVE, an endosomal PI3P marker, and competitive binding to PI3P via prolonged FYVE expression reduces the average number of Arc puncta per cell. Overexpression of MTMR1, a PI3P phosphatase, significantly reduces Arc capsid secretion. Arc capsids secrete through the endosomal-MVB axis as extracellular vesicles. Live-cell imaging shows that fluorescently labeled Arc primarily colocalizes Rab5 and CD63, early endosomal and MVB markers, respectively. Superresolution imaging resolves Arc accumulates within the intraluminal vesicles of MVB. CRISPR double knockout of RalA and RalB, crucial GTPases for MVB biogenesis and exocytosis, severely reduces Arc-mediated RNA transfer efficiency. These results suggest that, unlike the Human Immunodeficiency Virus Gag, which assembles on and bud off from the plasma membrane, Arc capsids assemble at the endocytic membranes of the endosomal-MVB pathway mediated by PI3P. Understanding Arcs secretion pathway helps gain insights into its role in intercellular cargo transfer and highlights the commonality and distinction of trafficking mechanisms between structurally resembled capsid proteins.

biophysics↗

bioRxiv2023

Curcumin alleviates Arsenic trioxide-induced behavioural impairment, oxidative damage & morphological alterations in striatal region of mice brain

Arsenic-induced neurotoxicity is well-documented in literature and reported to have dose-dependent damaging effects in the mice brain. Curcumin, a cost-effective plant polyphenol, safely demonstrates protective effects against arsenic-induced neurotoxicity by modifying oxidative stress, apoptosis, and neurochemistry in rodents brain. The present study determined the neuroprotective potential of curcumin (CUR) on adverse effects induced by arsenic trioxide (As2O3) in mice striatal region. Healthy adult male mice were chronically administered with varying concentrations of As2O3 (2, 4 & 8 mg/kg bw) alone and along with CUR (100 mg/kg bw) via oral route for 45 days. Towards the end of experimental period, the animals were subjected to behavioural paradigm including open field task, novel object recognition, rota-rod and morris water maze. Fresh striatal tissues were collected from the animals on day 46 for biochemical analysis such as MDA, GPx and GSH. While perfusion fixed brains were processed for morphological observations. Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to As2O3 compared to controls. Simultaneous treatment of As2O3 (2, 4 & 8 mg/kg bw) and curcumin (100 mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As2O3 alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of As2O3 (4 & 8 mg/kg bw). However, these changes were reversed in mice who received As2O3 + CUR co-treatment. Together, our findings provide preliminary evidence that curcumin protects mice striatal region from As2O3-induced behavioral, biochemical and morphological alterations.

pharmacology and toxicology↗