Publications by authors named "Khaga R Neupane"

3 Publications

  • Page 1 of 1

Nicotine induces morphological and functional changes in astrocytes via nicotinic receptor activity.

Glia 2021 Apr 14. Epub 2021 Apr 14.

Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA.

Nicotine is a highly addictive compound present in tobacco, which causes the release of dopamine in different regions of the brain. Recent studies have shown that astrocytes express nicotinic acetylcholine receptors (nAChRs) and mediate calcium signaling. In this study, we examine the morphological and functional adaptations of astrocytes due to nicotine exposure. Utilizing a combination of fluorescence and atomic force microscopy, we show that nicotine-treated astrocytes exhibit time-dependent remodeling in the number and length of both proximal and fine processes. Blocking nAChR activity with an antagonist completely abolishes nicotine's influence on astrocyte morphology indicating that nicotine's action is mediated by these receptors. Functional studies show that 24-hr nicotine treatment induces higher levels of calcium activity in both the cell soma and the processes with a more substantial change observed in the processes. Nicotine does not induce reactive astrocytosis even at high concentrations (10 μM) as determined by cytokine release and glial fibrillary acidic protein expression. We designed tissue clearing experiments to test whether morphological changes occur in vivo using astrocyte specific Aldh1l1-tdTomato knock in mice. We find that nicotine induces a change in the volume of astrocytes in the prefrontal cortex, CA1 of the hippocampus, and the substantia nigra. These results indicate that nicotine directly alters the functional and morphological properties of astrocytes potentially contributing to the underlying mechanism of nicotine abuse.
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http://dx.doi.org/10.1002/glia.24011DOI Listing
April 2021

Macrophage-Engineered Vesicles for Therapeutic Delivery and Bidirectional Reprogramming of Immune Cell Polarization.

ACS Omega 2021 Feb 26;6(5):3847-3857. Epub 2021 Jan 26.

Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, United States.

Macrophages, one of the most important phagocytic cells of the immune system, are highly plastic and are known to exhibit diverse roles under different pathological conditions. The ability to repolarize macrophages from pro-inflammatory (M1) to anti-inflammatory (M2) or offers a promising therapeutic approach for treating various diseases such as traumatic injury and cancer. Herein, it is demonstrated that macrophage-engineered vesicles (MEVs) generated by disruption of macrophage cellular membranes can be used as nanocarriers capable of reprogramming macrophages and microglia toward either pro- or anti-inflammatory phenotypes. MEVs can be produced at high yields and easily loaded with diagnostic molecules or chemotherapeutics and delivered to both macrophages and cancer cells and . Overall, MEVs show promise as potential delivery vehicles for both therapeutics and their ability to controllably modulate macrophage/microglia inflammatory phenotypes.
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http://dx.doi.org/10.1021/acsomega.0c05632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876833PMC
February 2021

Cell-Derived Vesicles for in Vitro and in Vivo Targeted Therapeutic Delivery.

ACS Omega 2019 Jul 24;4(7):12657-12664. Epub 2019 Jul 24.

Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, United States.

Efficient delivery of therapeutics across the cell membrane to the interior of the cell remains a challenge both in vitro and in vivo. Here, we demonstrate that vesicles derived from cellular membranes can be efficiently loaded with cargo that can then be delivered to the interior of the cell. These vesicles demonstrated cell-targeting specificity as well as the ability to deliver a wide range of different cargos. We utilized this approach to deliver both lipophilic and hydrophilic cargos including therapeutics and DNA in vitro. We further demonstrated in vivo targeting and delivery using fluorescently labeled vesicles to target tumor xenografts in an animal. Cell-derived vesicles can be generated in high yields and are easily loaded with a variety of cargos. The ability of these vesicles to specifically target the same cell type from which they originated provides an efficient means of delivering cargo, such as therapeutics, both in vitro and in vivo.
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http://dx.doi.org/10.1021/acsomega.9b01353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681979PMC
July 2019