Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury
Date
2021
Authors
Krukowski, Karen
Nolan, Amber
Becker, McKenna
Picard, Katherine
Vernoux, Nathalie
Frias, Elma S.
Feng, Xi
Rosi, Susanna
Tremblay, Marie-Ève
Journal Title
Journal ISSN
Volume Title
Publisher
Brain Behavior and Immunity
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.
Description
We 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.
Keywords
traumatic brain injury, microglia, neuroinflammation, learning and memory
Citation
Krukowski, 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