Nanoscale Surveillance of the Brain by Microglia via cAMP-Regulated Filopodia
This week we profile a recent publication in Cell Reports from Dr. Louis-Philippe Bernier (pictured)
in the laboratory of Dr. Brian MacVicar at the Djavad Mowafaghian Centre for Brain Health.
Can you provide a brief overview of your lab’s current research focus?
I’m a Research Associate in Dr. Brian MacVicar’s lab, where we study the complex functioning of the brain by looking at how its various cell types interact with each other. Neurons, glia and vascular cells all need to act in a coordinated manner to function properly, and we use multiple in situ and in vivo tools to study their interactions. The two main aspects I study are how microglia survey the brain environment in health and disease, and how perivascular cells like pericytes contribute to brain function and pathology. Although the roles of these cells are critical in physiological conditions to maintain brain homeostasis, we are particularly interested in how metabolic challenges such as stroke trigger changes in the behaviour and function of microglia and pericytes.
What is the significance of the findings in this publication?
Microglia are highly ramified cells that constantly extend and retract processes to probe their environment and respond to changes in homeostasis. In this project, we reveal that they interact with their neighbouring neurons and glial cells by using filopodia, or thin actin-rich protrusions located near the tip of the larger processes. We characterized the intracellular pathway directing the presence and growth of these filopodia, and show that they allow microglia to more efficiently sense changes in the environment in the nanoscale. This dual-scale baseline surveillance of the brain parenchyma by microglia is critical throughout life, and our work shows how affecting the fine balance it relies on can dramatically affect microglial immune functions.
What are the next steps for this research?
Since microglial morphology is so dynamic, it can be used to track microglial function in real-time under different physiological and pathological conditions. We are currently investigating how microglial filopodia and other cellular structures are altered during stroke, or when important nutrients like glucose are depleted from the environment. Microglia are the brain’s first responders, and as such need to perform critical immune functions in pathological conditions where energy supplies are low. Understanding the intracellular mechanisms driving microglial function is therefore key to identifying how pharmacological manipulations of microglia may improve their protective role, or dampen their neurotoxic actions following injury.
This work was funded by:
The Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, the Heart and Stroke Foundation and Fondation Leducq.