Cellular and Molecular Neuroscience, Immunology, Neurology, Neuroscience
20
Scopus Publications
2043
Scholar Citations
16
Scholar h-index
18
Scholar i10-index
Scopus Publications
Multimodal Nano-DESI Mass Spectrometry Imaging Reveals Phospholipids Accumulation in and around Amyloid Plaques in Alzheimer’s Disease Manxi Yang, Xindi Tang, Mushfeqa Iqfath, Emerson Hernly, Daisy Unsihuay, Palak Manchanda, Kaushik Sharma, Zihan Qu, Hang Hu, Connor Beveridge, Gaurav Chopra, Julia Laskin ACS Chemical Neuroscience, 2025 Alzheimer's disease (AD), characterized by β-amyloid plaques, is increasingly recognized by lipid dysregulation as a key factor in its pathology. Mass spectrometry imaging (MSI), a powerful tool for mapping the spatial distribution of biomolecules in tissue sections, is ideally suited for investigating region-specific molecular alterations in diseased animal tissues. Recent MSI advancements have revealed plaque-associated molecular features in the AD brain, highlighting the role of metabolic dysfunction in disease progression. In this study, we developed a novel multimodal MSI approach using nanospray desorption electrospray ionization (nano-DESI) for dual polarity mode lipid and peptide imaging in the brain tissues of 5-7-month-old transgenic familial AD mice (5xFAD), followed by fluorescence imaging of β-amyloid plaques on the same tissue section. Our results revealed the accumulation of several peptides and phospholipids, including phosphatidylethanolamines (PE), phosphatidylinositols (PI), phosphatidylglycerols (PG), and phosphatidylcholines (PC) in and/or surrounding β-amyloid plaques in the hippocampus, isocortex, and thalamus regions of the AD brain. Furthermore, we observed that several fatty acids (FAs) were enhanced in the plaque-enriched subiculum region of the hippocampus. Our results demonstrate the power of the multimodal nano-DESI MSI approach for comprehensive mapping of molecular pathology with high spatial resolution, providing unique insights into disease metabolism and potential biomarkers.
Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease Priya Prakash, Palak Manchanda, Evi Paouri, Kanchan Bisht, Kaushik Sharma, Jitika Rajpoot, Victoria Wendt, Ahad Hossain, Prageeth R. Wijewardhane, Caitlin E. Randolph, Yihao Chen, Sarah Stanko, Nadia Gasmi, Anxhela Gjojdeshi, Sophie Card, Jonathan Fine, Krupal P. Jethava, Matthew G. Clark, Bin Dong, Seohee Ma, Alexis Crockett, Elizabeth A. Thayer, Marlo Nicolas, Ryann Davis, Dhruv Hardikar, Daniela Allende, Richard A. Prayson, Chi Zhang, Dimitrios Davalos, Gaurav Chopra Immunity, 2025
Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice Kanchan Bisht, Kenneth A. Okojie, Kaushik Sharma, Dennis H. Lentferink, Yu-Yo Sun, Hong-Ru Chen, Joseph O. Uweru, Saipranusha Amancherla, Zainab Calcuttawala, Antony Brayan Campos-Salazar, Bruce Corliss, Lara Jabbour, Jordan Benderoth, Bria Friestad, William A. Mills, Brant E. Isakson, Marie-Ève Tremblay, Chia-Yi Kuan, Ukpong B. Eyo Nature Communications, 2021 Microglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 + myeloid cell somata and brain capillaries. We confirm that these cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then, we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing them with parenchymal microglia (PCMs) in their morphological activities including during microglial depletion and repopulation. Molecularly, we identify P2RY12 receptors as a regulator of CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, microglial elimination triggered capillary dilation, blood flow increase, and impaired vasodilation that were recapitulated in P2RY12−/− and PANX1−/− mice suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function.
A Comparative Biology of Microglia Across Species Kaushik Sharma, Kanchan Bisht, Ukpong B. Eyo Frontiers in Cell and Developmental Biology, 2021 Microglia are unique brain-resident, myeloid cells. They have received growing interest for their implication in an increasing number of neurodevelopmental, acute injury, and neurodegenerative disorders of the central nervous system (CNS). Fate-mapping studies establish microglial ontogeny from the periphery during development, while recent transcriptomic studies highlight microglial identity as distinct from other CNS cells and peripheral myeloid cells. This evidence for a unique microglial ontogeny and identity raises questions regarding their identity and functions across species. This review will examine the available evidence for microglia in invertebrate and vertebrate species to clarify similarities and differences in microglial identity, ontogeny, and physiology across species. This discussion highlights conserved and divergent microglial properties through evolution. Finally, we suggest several interesting research directions from an evolutionary perspective to adequately understand the significance of microglia emergence. A proper appreciation of microglia from this perspective could inform the development of specific therapies geared at targeting microglia in various pathologies.
Sex Differences of Microglia and Synapses in the Hippocampal Dentate Gyrus of Adult Mouse Offspring Exposed to Maternal Immune Activation Chin Wai Hui, Haley A. Vecchiarelli, Étienne Gervais, Xiao Luo, Félix Michaud, Lisa Scheefhals, Kanchan Bisht, Kaushik Sharma, Lisa Topolnik, Marie-Ève Tremblay Frontiers in Cellular Neuroscience, 2020 Schizophrenia is a psychiatric disorder affecting ∼1% of humans worldwide. It is earlier and more frequently diagnosed in men than woman, and men display more pronounced negative symptoms together with greater gray matter reductions. Our previous findings utilizing a maternal immune activation (mIA) mouse model of schizophrenia revealed exacerbated anxiety-like behavior and sensorimotor gating deficits in adult male offspring that were associated with increased microglial reactivity and inflammation in the hippocampal dentate gyrus (DG). However, both male and female adult offspring displayed stereotypy and impairment of sociability. We hypothesized that mIA may lead to sex-specific alterations in microglial pruning activity, resulting in abnormal synaptic connectivity in the DG. Using the same mIA model, we show in the current study sex-specific differences in microglia and synapses within the DG of adult offspring. Specifically, microglial levels of cluster of differentiation (CD)68 and CD11b were increased in mIA-exposed females. Sex-specific differences in excitatory and inhibitory synapse densities were also observed following mIA. Additionally, inhibitory synaptic tone was increased in DG granule cells of both males and females, while changes in excitatory synaptic transmission occurred only in females with mIA. These findings suggest that phagocytic and complement pathways may together contribute to a sexual dimorphism in synaptic pruning and neuronal dysfunction in mIA, and may propose sex-specific therapeutic targets to prevent schizophrenia-like behaviors.
Precise brain mapping to perform repetitive in vivo imaging of neuro-immune dynamics in mice Kanchan Bisht, Kaushik Sharma, Ukpong B. Eyo Journal of Visualized Experiments, 2020 cells, this protocol demonstrates the ability of this technique to allow repetitive visualization of cellular dynamics in the same brain location over extended time periods, that can further aid in understanding the structural and functional responses of these cells in normal physiology or following pathological insults. Where necessary, this approach can be coupled to functional imaging of neural cells, e.g., with calcium imaging. This approach is especially a powerful technique to visualize the physical interaction between different cell types of the CNS in vivo when genetic mouse models or specific dyes with distinct fluorescent tags to label the cells of interest are available.
Dark microglia: A new phenotype predominantly associated with pathological states Kanchan Bisht, Kaushik P. Sharma, Cynthia Lecours, Maria Gabriela Sánchez, Hassan El Hajj, Giampaolo Milior, Adrián Olmos‐Alonso, Diego Gómez‐Nicola, Giamal Luheshi, Luc Vallières, Igor Branchi, Laura Maggi, Cristina Limatola, Oleg Butovsky, Marie‐Ève Tremblay GLIA, 2016
Dark microglia: Why are they dark? Kanchan Bisht, Kaushik Sharma, Baptiste Lacoste, Marie-Ève Tremblay Communicative and Integrative Biology, 2016
Multimodal Nano-DESI Mass Spectrometry Imaging Reveals Phospholipids Accumulation in and around Amyloid Plaques in Alzheimer’s Disease M Yang, X Tang, M Iqfath, E Hernly, D Unsihuay, P Manchanda, ... ACS Chemical Neuroscience 16 (16), 3127-3137 , 2025 2025 Citations: 6
Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease P Prakash, P Manchanda, E Paouri, K Bisht, K Sharma, J Rajpoot, ... Immunity 58 (6), 1536-1552. e8 , 2025 2025 Citations: 67
Amyloid β induces lipid droplet-mediated microglial dysfunction in Alzheimer’s disease P Prakash, P Manchanda, E Paouri, K Bisht, K Sharma, J Rajpoot, ... BioRxiv, 2023.06. 04.543525 , 2024 2024 Citations: 41
Dark microglia are abundant in normal postnatal development, where they remodel synapses via phagocytosis and trogocytosis, and are dependent on TREM2 HA Vecchiarelli, K Bisht, K Sharma, S Weiser Novak, ME Traetta, ... BioRxiv, 2024.10. 15.618087 , 2024 2024 Citations: 10
Ketogenic diet changes microglial morphology and the hippocampal lipidomic profile differently in stress susceptible versus resistant male mice upon repeated social defeat FG Ibáñez, T Halvorson, K Sharma, CG McKee, M Carrier, K Picard, ... Brain, behavior, and immunity 114, 383-406 , 2023 2023 Citations: 27
Ketogenic diet alters microglial morphology and changes the hippocampal lipidomic profile distinctively in stress susceptible versus resistant male mice upon repeated social defeat FG Ibáñez, T Halvorson, K Sharma, C McKee, M Carrier, K Picard, ... bioRxiv , 2023 2023 Citations: 3
Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice K Picard, K Bisht, S Poggini, S Garofalo, MT Golia, B Basilico, F Abdallah, ... Brain, Behavior, and Immunity 97, 423-439 , 2021 2021 Citations: 98
Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice K Bisht, KA Okojie, K Sharma, DH Lentferink, YY Sun, HR Chen, ... Nature communications 12 (1), 5289 , 2021 2021 Citations: 339
A comparative biology of microglia across species K Sharma, K Bisht, UB Eyo Frontiers in cell and developmental biology 9, 652748 , 2021 2021 Citations: 53
P. 709 Ketogenic diet modulates microglial properties at steady-state and promotes resilience to repeated social defeat stress in adult mice FG Ibanez, K Sharma, K Picard, K Bisht, N Vernoux, ME Tremblay European Neuropsychopharmacology 40, S403-S404 , 2020 2020
Sex differences of microglia and synapses in the hippocampal dentate gyrus of adult mouse offspring exposed to maternal immune activation CW Hui, HA Vecchiarelli, É Gervais, X Luo, F Michaud, L Scheefhals, ... Frontiers in Cellular Neuroscience 14, 558181 , 2020 2020 Citations: 75
رسم خرائط دقيقة للدماغ لأداء المتكررة في التصوير فيفو من ديناميات العصبية المناعية في الفئران K Bisht, K Sharma, UB Eyo Journal of Visualized Experiments (JoVE), e61454 , 2020 2020
Precise brain mapping to perform repetitive in vivo imaging of neuro-immune dynamics in mice K Bisht, K Sharma, UB Eyo J. Vis. Exp 10 (61454), 10.3791 , 2020 2020 Citations: 4
Microglia: Multiple states and multiple roles in the normal and diseased brain and spinal cord K Sharma, ME Tremblay Neuroscience letters 729, 135019 , 2020 2020 Citations: 2
Calming neurons with a microglial touch K Sharma, LJ Wu, UB Eyo Trends in neurosciences 43 (4), 197-199 , 2020 2020 Citations: 16
Fare Beyninde Mikroglial Yoğunluk, Morfoloji ve Periferik Miyeloid Hücre Infiltrasyonu Analizi için IBA1 ve TMEM119 Kullanılarak İmmünofloresanS Boyama FG Ibanez, K Picard, M Bordeleau, K Sharma, K Bisht, MÈ Tremblay Journal of Visualized Experiments (JoVE), e60510 , 2019 2019
Immunofluorescence צביעת באמצעות IBA1 ו TMEM119 עבור צפיפות Microglial, מורפולוגיה וניתוח הסתננות מיאלואידית תא היקפית במוח העכבר FG Ibanez, K Picard, M Bordeleau, K Sharma, K Bisht, MÈ Tremblay Journal of Visualized Experiments (JoVE), e60510 , 2019 2019
تلطيخ المناعية باستخدام IBA1 و TMEM119 لكثافة Microglial، المورفولوجية والطرفية الخلية النخاعية تحليل تسلل في الدماغ الماوس FG Ibanez, K Picard, M Bordeleau, K Sharma, K Bisht, MÈ Tremblay Journal of Visualized Experiments (JoVE), e60510 , 2019 2019
Immunfluoreszenzfärbung mit IBA1 und TMEM119 für Mikroglia-Dichte, Morphologie und periphere Myeloid-Zellinfiltrationsanalyse im Maushirn FG Ibanez, K Picard, M Bordeleau, K Sharma, K Bisht, MÈ Tremblay Journal of Visualized Experiments (JoVE), e60510 , 2019 2019
Immunofluorescenza Colorazione utilizzando IBA1 e TMEM119 per densità microgliale, morfologia e infiltrazione delle cellule mieloidi periferiche nel cervello del mouse FG Ibanez, K Picard, M Bordeleau, K Sharma, K Bisht, MÈ Tremblay Journal of Visualized Experiments (JoVE), e60510 , 2019 2019
MOST CITED SCHOLAR PUBLICATIONS
Dark microglia: a new phenotype predominantly associated with pathological states K Bisht, KP Sharma, C Lecours, M Gabriela Sánchez, H El Hajj, G Milior, ... Glia 64 (5), 826-839 , 2016 2016 Citations: 489
Chronic stress as a risk factor for Alzheimer's disease: roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress K Bisht, K Sharma, MÈ Tremblay Neurobiology of stress 9, 9-21 , 2018 2018 Citations: 472
Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice K Bisht, KA Okojie, K Sharma, DH Lentferink, YY Sun, HR Chen, ... Nature communications 12 (1), 5289 , 2021 2021 Citations: 339
Immunofluorescence staining using IBA1 and TMEM119 for microglial density, morphology and peripheral myeloid cell infiltration analysis in mouse brain FG Ibanez, K Picard, M Bordeleau, K Sharma, K Bisht, MÈ Tremblay JoVE (Journal of Visualized Experiments), e60510 , 2019 2019 Citations: 124
Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice K Picard, K Bisht, S Poggini, S Garofalo, MT Golia, B Basilico, F Abdallah, ... Brain, Behavior, and Immunity 97, 423-439 , 2021 2021 Citations: 98
Sex differences of microglia and synapses in the hippocampal dentate gyrus of adult mouse offspring exposed to maternal immune activation CW Hui, HA Vecchiarelli, É Gervais, X Luo, F Michaud, L Scheefhals, ... Frontiers in Cellular Neuroscience 14, 558181 , 2020 2020 Citations: 75
Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease P Prakash, P Manchanda, E Paouri, K Bisht, K Sharma, J Rajpoot, ... Immunity 58 (6), 1536-1552. e8 , 2025 2025 Citations: 67
Microglia under psychosocial stressors along the aging trajectory: consequences on neuronal circuits, behavior, and brain diseases L Tian, CW Hui, K Bisht, Y Tan, K Sharma, S Chen, X Zhang, ... Progress in Neuro-Psychopharmacology and Biological Psychiatry 79, 27-39 , 2017 2017 Citations: 54
A comparative biology of microglia across species K Sharma, K Bisht, UB Eyo Frontiers in cell and developmental biology 9, 652748 , 2021 2021 Citations: 53
Dark microglia: Why are they dark? K Bisht, K Sharma, B Lacoste, MÈ Tremblay Communicative & integrative biology 9 (6), e1230575 , 2016 2016 Citations: 46
Amyloid β induces lipid droplet-mediated microglial dysfunction in Alzheimer’s disease P Prakash, P Manchanda, E Paouri, K Bisht, K Sharma, J Rajpoot, ... BioRxiv, 2023.06. 04.543525 , 2024 2024 Citations: 41
Microglia in the developing prefrontal cortex of rats show dynamic changes following neonatal disconnection of the ventral hippocampus CW Hui, SK Bhardwaj, K Sharma, AT Joseph, K Bisht, K Picard, ... Neuropharmacology 146, 264-275 , 2019 2019 Citations: 35
Feedback mechanism in depolarization-induced sustained activation of extracellular signal-regulated kinase in the hippocampus C Maharana, KP Sharma, SK Sharma Scientific reports 3 (1), 1103 , 2013 2013 Citations: 29
Ketogenic diet changes microglial morphology and the hippocampal lipidomic profile differently in stress susceptible versus resistant male mice upon repeated social defeat FG Ibáñez, T Halvorson, K Sharma, CG McKee, M Carrier, K Picard, ... Brain, behavior, and immunity 114, 383-406 , 2023 2023 Citations: 27
Depolarization induces acetylation of histone H2B in the hippocampus C Maharana, KP Sharma, SK Sharma Neuroscience 167 (2), 354-360 , 2010 2010 Citations: 27
Histone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memory K Pandey, KP Sharma, SK Sharma Learning & Memory 22 (10), 514-518 , 2015 2015 Citations: 20
Calming neurons with a microglial touch K Sharma, LJ Wu, UB Eyo Trends in neurosciences 43 (4), 197-199 , 2020 2020 Citations: 16
Dark microglia are abundant in normal postnatal development, where they remodel synapses via phagocytosis and trogocytosis, and are dependent on TREM2 HA Vecchiarelli, K Bisht, K Sharma, S Weiser Novak, ME Traetta, ... BioRxiv, 2024.10. 15.618087 , 2024 2024 Citations: 10
Multimodal Nano-DESI Mass Spectrometry Imaging Reveals Phospholipids Accumulation in and around Amyloid Plaques in Alzheimer’s Disease M Yang, X Tang, M Iqfath, E Hernly, D Unsihuay, P Manchanda, ... ACS Chemical Neuroscience 16 (16), 3127-3137 , 2025 2025 Citations: 6
Mechanisms of cAMP-induced sustained activation of extracellular signal-regulated kinase in the hippocampus KP Sharma, JB Singh, SK Sharma Neuroreport 25 (7), 470-474 , 2014 2014 Citations: 6