Benoit Labonté, Ph.D.
Assistant Professor, Université Laval
Research chair in partnership with Sentinel North - Molecular Neurobiology of Mood Disorders.
Discoveries about differences in the brains of depressed men and women
Dr. Benoit Labonté's research aims to understand the biological basis of depression and other mood disorders, with a specific focus on sex differences. Although depression is twice as common in women, most preclinical studies have been conducted primarily in males. Dr. Labonté's research has recently shown that genes expressed in the brains of model animals and humans with depression are very different in the two sexes.
Dr. Labonté's research focuses on mouse models of mood disorders, but his results have been confirmed by the analysis of human samples from brain banks and blood tests. These studies have identified genes and proteins that are specifically activated or repressed in depressed males or females. These genes constitute therapeutic targets that could be used to treat this disease in a personalized fashion.
Finally, studies in the Labonté laboratory also aim to understand the neural circuits involved in the regulation of mood. By combining multiple cellular and molecular approaches, his team can understand the contribution that certain neuronal populations make to the expression of depressive behaviors.
It is therefore in the context of developing better, more targeted therapeutic approaches to treat men and women that Dr. Labonté's team aims to improve our understanding of the molecular mechanisms underlying mood disorders.
In my lab, we are interested in identifying the molecular programs associated with the expression of mood disorders with a particular interest in defining sex differences. We aim at characterizing the role these molecular programs have on behavioral regulation by using well-validated mouse models of stress, known to reproduce both the phenotypic and molecular alterations found in males and females suffering from mood disorders. We use various approaches to identify and isolate neuronal populations functionally associated with stress response in both sexes. We also modify these molecular programs into a cell-specific fashion and aim at reversing the behavioral consequences of chronic stress in males and females. Overall, the overarching objectives of my laboratory are to provide a better understanding of the sexual dimorphism characterizing the molecular mechanisms responsible for the expression of mood disorders and to develop better and more targeted therapeutic approaches for their treatment in males and females.
To do so, we put forward a multidisciplinary and translational approach capitalizing on the comparative analysis of human and animal samples (post-mortem brain, blood samples). The stress models we use in male and female mice are chronic variable stress, chronic social defeat, and social isolation, all of which are evaluated through a battery of behavioral tests. Using different viral approaches in transgenic mouse lines, we map neuronal networks taking place across brain regions. We capitalize on these viral approaches to stimulate specific neuronal populations (optogenetics, dreadds) and isolate them (FACS, ribotag) before extracting their genetic material (RNA, DNA, ChIP) for further molecular analyses. We use genome-wide sequencing methods (RNAseq, ChIPseq) combined with cutting-edge bioinformatics analyses to characterize the transcriptional and epigenetic organization of gene networks in different cellular populations in both sexes that we then compare across species. We also use various viral approaches (viral-mediated gene transfer) to modify the expression of specific genes within precise cellular populations and determine their behavioral contribution in regulating stress responses in both males and females.
Our research interests are oriented toward the 3 following objectives:
- Determine the PFC connectome and evaluate the functional and behavioral contribution of the different neuronal populations projecting to the PFC in males and females following chronic stress.
- Determine the transcriptional organization of gene networks across the different neuronal populations projecting directly onto PFC neurons and evaluate the behavioral contribution of key hub genes in a sex- and cell-type- specific fashion.
- Determine the epigenetic signatures associated with the transcriptional reorganization of gene networks specific to the different neuronal populations projecting onto PFC neurons in males and females following chronic stress.
Research Chair Pfizer and Centre de Recherche de l’Institut Universitaire en Santé Mentale de Québec (2016-2021)
Molecular mechanisms underlying stress responses in males and females
