Investigations des interactions de la microglie-astrocyte dans la maladie d'Alzheimer

 

Keith Murai

Institut de recherche du centre universitaire de santé McGill

 

Domaine : Neurosciences, santé mentale et toxicomanies

Fonds d'innovation Pfizer-FRQS

Concours 2013-2014

Currently, over 100,000 individuals suffer from Alzheimer¿s disease in Quebec. Over the course of the next generation it is estimated that this number could reach a staggering 260,000 (Alzheimer Society of Canada). Besides the significant social burden that AD places upon society, there are also overwhelming financial burdens that need to be considered. Because there is currently no cure for AD, further investment in research is needed to reach a better understanding of the underlying causes of the disease and aid the design of new therapies that can block its onset or slow its progression. AD is difficult to understand because the causes are likely multi-factorial and the molecular and cellular pathways involved are complex. Neuronal loss is clearly an important cause of the severe cognitive deficits in AD. However, emerging evidence suggests that altered glial cell activity in the brain might be a contributing factor. Glial cells were originally viewed as passive support cells for neurons in the central nervous system. However, studies have discovered that glial cells are more dynamic than first thought and fundamental to neuronal and brain function.

This grant will focus on the hypothesis that the inter-communication of two glial cell types in the brain, microglia and astrocytes, plays a critical role in AD. In order to test this, we will investigate the crosstalk between microglia and astrocytes in a mouse model of AD. We will implement cutting-edge techniques to visualize glial cells, neurons, and beta-amyloid plaques in AD-like mouse brains at different stages of the disease, and compare the neuron-glial relationships found in such models to those occuring in brain tissues from AD patients. This research has the potential to expose new mechanisms involved in the propagation of AD and help to build glial-based therapeutic strategies for the treatment of AD.