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

TitleNovel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury.
Publication TypeJournal Article
Year of Publication2021
AuteursKrukowski, K, Nolan, A, Becker, MK, Picard, K, Vernoux, N, Frias, ES, Feng, X, Tremblay, M-È, Rosi, S
JournalBrain Behav Immun
Volume98
Pagination122-135
Date Published2021 11
ISSN1090-2139
KeywordsAnimals, Brain, Brain Injuries, Traumatic, Cognitive Dysfunction, Disease Models, Animal, Mice, Mice, Inbred C57BL, Microglia
Abstract

Traumatic 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.

DOI10.1016/j.bbi.2021.08.210
Alternate JournalBrain Behav Immun
PubMed ID34403733