Biology subjects

Biswas, S. R.

Publications and source records attributed to Biswas, S. R..

3 recordsLinked to original sources

bioRxiv2025

Brain injury contributes to dopaminergic neurodegeneration, Lewy body pathology, and Parkinsonism preclinically with outcomes altered by T cell modulation

Traumatic brain injury (TBI) increases the risk of Parkinsons disease (PD) development later in life, but much remains unknown regarding the mechanisms driving this relationship. A single, mild brain injury triggers resident and peripheral neuroinflammatory pathways that are similarly activated in PD patients, which could possibly increase susceptibility to neurodegeneration. In this study, we used preclinical mouse models of mild TBI (mTBI) and PD to evaluate how injury-induced immune signaling may exacerbate PD-associated pathologies. Dopaminergic (DA) neurons showed upregulation of genes associated with neuroinflammation, adaptive immunity, and PD following mTBI. mTBI caused degeneration of DA neurons in the substantia nigra (SN) and increased the spread of Lewy body (LB) pathology to other brain regions, such as the ipsilateral cortex, in a preclinical model of PD. Reducing adaptive immune infiltration into the central nervous system (CNS) with a transgenic model lacking mature lymphocytes, or directly by in vivo depletion of T cells or B cells individually, improved neurodegenerative outcomes of DA neurons following brain injury. Our results indicate the possibility of a sustained, chronic peripheral immune cell infiltration which negatively affects both DA neurons and alpha synuclein (-syn) fibril propagation, providing insight on therapeutic windows to reduce DA neuron vulnerability.

neuroscience↗

bioRxiv2025

Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh Syndrome mice

Leigh syndrome (LS) is a complex, genetic mitochondrial disorder defined by neurodegenerative phenotypes with pediatric manifestation. However, recent clinical studies report behavioral phenotypes in human LS patients that are more reminiscent of neurodevelopmental delays. To determine if disruptions in epochs of rapid brain growth during infancy precede the hallmark brain lesions that arise during childhood, we evaluated neural and glial precursor cellular dynamics in a mouse model of LS. Single cell RNA sequencing along with histological and anatomical assessments were performed in NDUFS4 KO mice and compared with controls to determine the impact of Complex I deficiency on neural stem cells, their neuronal and oligodendroglial progeny, lineage progression, and overt differences in specific brain regions. Our findings show disruptions in all categories, specifically within the subventricular zone and corpus callosum. Given that LS is purely considered a neurodegenerative disease, we propose that mitochondrial dysfunction is a neurodevelopmental signature predating classic diagnosis in LS.

neuroscience↗

bioRxiv2021

Vibrio cholerae El Tor strains linked to global cholera are homogeneous by pulsed-field gel electrophoresis

Vibrio cholerae O1 El Tor, causative agent of the ongoing seventh cholera pandemic, is native to the aquatic environment of the Ganges Delta, Bay of Bengal (GDBB). Recent studies traced pandemic strains to the GDBB and proposed global spread of cholera had occurred via intercontinental transmission. In the research presented here, NotI-digested genomic DNA extracted from V. cholerae O1 clinical and environmental strains isolated in Bangladesh during 2004 - 2014 was analyzed by pulsed-field gel electrophoresis (PFGE). Results of cluster analysis showed 94.67% of the V. cholerae isolates belonged to clade A and included the majority of clinical isolates of spatio-temporal origin and representing different cholera endemic foci. The rest of the strains were estuarine, all environmental isolates from Mathbaria, Bangladesh, and occurred as singletons, clustered in clades B and C, or in the small clades D and E. Cluster analysis of the Bangladeshi strains and including 157 El Tor strains from thirteen countries in Asia, Africa, and the Americas revealed 85% of the total set of isolates belonged to clade A, indicating all were related, yet did not form an homogeneous cluster. Overall, 15% of the global strains comprised multiple small clades or segregated as singletons. Three sub-clades could be discerned within the major clade A, reflecting distinct lineages of V. cholerae El Tor associated with cholera in Asia, Africa, and the Americas. The presence in Asia and the Americas of non-pandemic V. cholerae El Tor populations differing by PFGE and from strains associated with cholera globally suggests different ecotypes are resident in distant geographies. Author SummaryCholera is a major health threat, especially in the Ganges Delta, Bay of Bengal (GDBB). Vibrio cholerae, causative agent of cholera, is native to the GDBB aquatic environment. Recent genomic studies suggest GDBB is the cholera hotspot where the disease spreads globally via human activity. Pulsed-field gel electrophoresis (PFGE) of NotI-digested genomic DNA from V. cholerae El Tor endemic cholera strains was done, including Bangladesh aquatic environment and clinical strains from distant geographical regions representing three cholera-prone continents. Results showed the majority of pandemic strains belonged to a major cluster, suggesting clonal relatedness. Ecotypes were detected, indicating geographically specific lineages. It is concluded that epidemic strains in Bangladesh and thirteen countries of Asia, Africa, and the Americas are geographically adapted, with independent evolution of the bacterium in respective geographical regions.

molecular biology↗