¹University of Victoria, Division of Medical Sciences, Victoria, Canada

Background: A series of discoveries spanning the last two decades has shifted our view of microglia, the brain's immune cells, by showing their essential but previously unexpected contribution to brain development, as well as their important functions in learning and memory, and in behavioural adaptation to various environmental challenges (pollution, stress, inadequate nutrition, viral infection, etc.) during life. In this emergent field of investigation, which is currently experiencing exponential growth, our research project aims to investigate the roles of "dark microglia", a particular microglial state that we have discovered, and which may be specifically involved in proper neurodevelopment via remodelling of brain blood vessels (vasculature) and synapses, the connections between neurons.

Aims & Objectives: We aim to study the roles of dark microglia during normal development and in the context of maternal immune activation, a process associated with the onset of various neurodevelopmental and neuropsychiatric diseases in human patients. We focus our investigation on studying the long-term consequences of maternal viral infection-induced immune activation throughout development into adulthood.

Method: This research is conducted using a combination of cutting-edge mouse models, longitudinal behavioural testing, correlative microscopy (e.g., epifluorescence, confocal and state-of-the-art 2D and 3D-scanning electron microscopy), together with multi-omics. This integrative approach allows the Tremblay Lab to study the outcomes of various environmental risk factors and lifestyle elements on microglial properties and diversity along the aging trajectory. Targeted interventions are also performed.

Results: Our unpublished findings reveal differences in the structure and function of different microglial states that could play critical roles during development in health and maternal immune activation.

Discussion & Conclusions: This research into dark microglia's involvement in vascular and synaptic remodelling during normal development and upon maternal immune activation, an important environmental risk factor for human diseases, will bridge metabolism and immunity for the future prevention and/or treatment of several neurodevelopmental and neuropsychiatric disorders, including schizophrenia.