Centre de recherche du CHU de Québec, Canada
Glial Physiology and Neurodegeneration
Title of the talk:
Structural relationships between microglia & synapses in contexts of neuroinflammation.
During her training, Marie-Eve Tremblay developed expertise in non-invasive imaging to study the physiological roles of glial cells throughout the lifespan. Since glial cells are highly reactive to changes in homeostasis, non-invasive methods that prevent their phenotypic transformation during experimental procedures are required to study their physiological roles. Using these techniques, her postdoctoral work revealed that microglia, the resident immune cells of the brain, actively remodel neuronal circuits (by phagocytosis of pre-synaptic axon terminals and post-synaptic dendritic spines) during normal physiological conditions. As an independent investigator, she is now exploring the significance of this new cellular mechanism which could represent the missing link between neuroinflammation and cognitive dysfunction in the pathogenesis of diseases. In particular, her research focusses on elucidating the roles of microglia in the loss of synapses which best correlates with the impairment of learning and memory across chronic stress, aging, and various pathological conditions. In complement, she is investigating the involvement of bone marrow-derived myeloid cells which infiltrate the brain through the vasculature, to provide further insights into the relationship between the brain and body across homeostasis, plasticity and disease. She is also studying additional physiological roles of microglia and other myeloid cell types in the brain, as well as their dysregulation upon chronic stress, depression, schizophrenia, aging, and neurodegenerative diseases to identify new pathogenic mechanisms. This work is conducted using a longitudinal approach that combines non-invasive chronic two-photon in vivo imaging –structural and functional– with superesolution microscopy, correlative 3D-scanning electron microscopy, and behavioural assessments. Her long-term goal is to help develop new therapies using myeloid cells as vectors for effecting targeted changes in neuronal circuits, in order to spare memories, learning and other cognitive functions.