Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2018-2019)

Introduction : Until the 1990s, astrocytes were largely considered to be passive components of the central nervous system, providing mainly structural support for neurons. It is now clear that astrocytes are highly dynamic cells that play a variety of roles that are essential for the proper function of cerebral networks. However, our current knowledge on the morpho-functional properties of these cells comes essentially from studies conducted with animal models, rodents in particular. Despite the many similarities in the basic organization of rodent and human brains, significant differences can exist at the cellular level. Our work as well as that of other groups have recently shown that cortical astrocytes are much more complex and diverse than their rodent counterparts. Despite these recent findings, much remains to be discovered regarding the cellular and subcellular organization and molecular properties of astrocytes in the human brain. In particular, virtually nothing is known about the morphometric and molecular features of astrocytes in other, non-cortical, brain regions.

Main and specific objectives : The main objective of this research program will be to characterize the anatomical and gene expression profiles of astrocytic subtypes found in different regions of the human brain (neocortex, allocortex, thalamus, basal ganglia, brainstem). More specifically, we will use fine anatomical and molecular approaches to (i) describe qualitatively and quantitatively the distribution and morphometric (cellular and subcellular) properties of astrocytes in each region, and (ii) characterize the regional astrocytic gene expression profiles (transcriptomics).

Methods : Well-characterized fixed and frozen postmortem brain samples will be obtained from the Douglas-Brain Canada Brain Bank. These samples will come from healthy 35-40 year-old male and female donors with no history of psychiatric, neurological, or chronic inflammatory conditions. State-of-the-art approaches routinely used in my laboratory will be employed to quantify regional astrocytic densities and morphologies. These include stereological quantifications of GFAP-immunostained cells and 3D reconstructions of Golgi-stained astrocytes. In each region, astrocytes will be extracted by laser-capture microdissection, and their expression profiles determined by ultra-low input RNA sequencing.

Significance : By characterizing the morphometric and gene expression profiles of astrocytes in various brain regions, this research will provide the first comprehensive description of cerebral astrocytic subtypes in humans. This will allow the field to better understand the cellular organization of human brain circuits, as well as the implication of astrocytes in the function of these circuits.