Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury

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dc.contributor.authorKrukowski, Karen
dc.contributor.authorNolan, Amber
dc.contributor.authorBecker, McKenna
dc.contributor.authorPicard, Katherine
dc.contributor.authorVernoux, Nathalie
dc.contributor.authorFrias, Elma S.
dc.contributor.authorFeng, Xi
dc.contributor.authorRosi, Susanna
dc.contributor.authorTremblay, Marie-Ève
dc.date.accessioned2024-03-20T15:48:53Z
dc.date.available2024-03-20T15:48:53Z
dc.date.issued2021
dc.descriptionWe are grateful to Dr. Sachiko Sato and Julie-Christine Lévesque at the Bioimaging Platform of Centre de recherche du CHU de Québec-Université Laval, as well as Audrey Gagné for her help with electron microscopy imaging and Maude Bordeleau for her help with statistical analyses. Microscopic images were obtained at the Nikon Imaging Center at UCSF. Schematic diagrams in figures created in Biorender.com.
dc.description.abstractTraumatic brain injury (TBI) is one of the leading causes of long-term neurological disability in the world. Currently, there are no therapeutics for treating the deleterious consequences of brain trauma; this is in part due to a lack of complete understanding of cellular processes that underlie TBI-related pathologies. Following TBI, microglia, the brain resident immune cells, turn into a "reactive" state characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Utilizing multimodal, state-of-the-art techniques that widely span from ultrastructural analysis to optogenetic interrogation of circuit function, we investigated the reactive microglia phenotype one week after injury when learning and memory deficits are also measured. Microglia displayed increased: (i) phagocytic activity in vivo, (ii) synaptic engulfment, (iii) increased neuronal contact, including with dendrites and somata (termed 'satellite microglia'). Functionally, satellite microglia might impact somatic inhibition as demonstrated by the associated reduction in inhibitory synaptic drive. Cumulatively, here we demonstrate novel microglia-mediated mechanisms that may contribute to synaptic loss and cognitive impairment after traumatic brain injury.
dc.description.reviewstatusReviewed
dc.description.scholarlevelFaculty
dc.description.sponsorshipThis work was supported by the NIH/National Institute on Aging Grant R01AG056770 (to S.R.), the NIH/National Cancer Institute Grant R01 R01CA246722 (to S.R), the NRSA post-doctoral fellowship from the NIA F32AG054126 (to K.K), the National Institute for General Medicine (NIGMS) Initiative for Maximizing Student Development (R25GM056847) and the National Science Foundation (NSF) Graduate Fellowship Program (To E.S.F), the UCSF Clinical and National Center for Advanced Translational Sciences at NIH (UCSF-CTSI Grant Number TL1 TR001871) and the NIH/NINDS (K08NS114170) (To A.N). K.P. was supported by a doctoral scholarship from Fonds de recherche du Québec – Santé, an excellence award from Fondation du CHU de Québec, as well as from Centre thématique de recherche en neurosciences and from Fondation Famille-Choquette. This study was funded by a Canadian Institutes of Health Research Foundation Grant (148420) and Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (RGPIN-2014-05308) awarded to M.E.T. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition. The San Francisco General Hospital Flow Core Facility was supported by the National Institutes of Health (P30 AI027763).
dc.identifier.citationKrukowski, K., Nolan, A., Becker, M., Picard, K., Vernoux, N., Frias, E. S., ... Rosi, S. (2021). Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury. Brain Behavior and Immunity, 98, 122-135. https://doi.org/10.1016/j.bbi.2021.08.210
dc.identifier.urihttps://doi.org/10.1016/j.bbi.2021.08.210
dc.identifier.urihttps://hdl.handle.net/1828/16228
dc.language.isoen
dc.publisherBrain Behavior and Immunity
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjecttraumatic brain injury
dc.subjectmicroglia
dc.subjectneuroinflammation
dc.subjectlearning and memory
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleNovel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
dc.typeArticle

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