Biology subjects

Jethava, K. P.

Publications and source records attributed to Jethava, K. P..

3 recordsLinked to original sources

bioRxiv2025

Impact Induces Phagocytic Defect in Reactive Microglia

We have developed traumatic brain injury (TBI)-on-a-chip in vitro models using primary microglia and neuronal networks and recorded the molecular and cellular changes following impact to represent impact injury. Using a pH-responsive amyloid {beta} (A{beta}pH), we showed that microglial phagocytosis was reduced at 7 days post-impact on the chip. Simultaneously, neurons increased their uptake of A{beta}, and decreased neuronal firing frequency at 7 days post-impact based on electrophysiological recordings. Given the importance of lipid metabolism in brain trauma and neurodegeneration, the lipidome secreted by impacted cells was analyzed to understand changes in cellular processes. Interestingly, many lipid species from the sphingomyelin, glycerophospholipid, and phosphatidylserine classes were significantly affected by impact, which are known to play important roles in the resolution of neuroinflammation and the pathogenesis of neurodegeneration.

neuroscience↗

bioRxiv2021

One Scaffold - Different Organelles Sensors: pH-Activable Fluorescent Probes for Targeting Live Primary Microglial Cell Organelles

Targeting live cell organelles is important for imaging and to understand and control specific biochemical processes. Typically, fluorescent probes with distinct structural scaffolds have been used for targeting specific cell organelle. Herein, we aimed to design modular one-step synthetic strategies using a common reaction intermediate to develop new lysosomal, mitochondrial and nucleus targeting pH-activable fluorescent probes that are all based on a single boron dipyrromethane analogs. The divergent cell organelle targeting was achieved by synthesizing pH-activable fluorescent probes with specific functional groups changes to the main scaffold resulting in differential fluorescence and pKa. Specifically, we show that the functional group transformation of the same scaffold influences cellular localization and specificity of pH-activable fluorescent probes in live primary microglial cells with pKas ranging from ~4.5-6.0. We introduce a structure-organelle-relationship (SOR) framework targeting the nucleus (NucShine), lysosomes (LysoShine) and mitochondria (MitoShine) in primary mouse microglial cells. This work will result in future applications of SOR beyond imaging to target and control organelle-specific biochemical processes in disease-specific models.

biochemistry↗

bioRxiv2020

Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time

Phagocytosis by glial cells is essential to regulate brain function during development and disease. Given recent interest in using amyloid {beta} (A{beta})-targeted antibodies as a therapy for patients with Alzheimers disease, removal of A{beta} by phagocytosis is likely protective early in Alzheimers disease, but remains poorly understood. Impaired phagocytic function of glial cells surrounding A{beta} plaques during later stages in Alzheimers disease likely contributes to worsened disease outcomes, but the underlying mechanisms of how this occurs remain unknown. We have developed a human A{beta}1-42 analogue (A{beta}pH) that exhibits green fluorescence upon internalization into the acidic phagosomes of cells but is non-fluorescent at physiological pH. This allowed us to image, for the first time, glial uptake of A{beta}pH in real time in live animals. Microglia phagocytose more A{beta}pH than astrocytes in culture, in brain slices and in vivo. A{beta}pH can be used to investigate the phagocytic mechanisms removing A{beta} from the extracellular space, and thus could become a useful tool to study A{beta} clearance at different stages of Alzheimers disease.

neuroscience↗