Impact du stress sur l'épileptogénèse et différences du développement de l'hippocampe entre les sexes

 

Daniele Wolf

Centre hospitalier universitaire Sainte Justine

 

Domaine : santé différentielle des sexes

Programme Formation de doctorat

Concours 2018-2019

Partenaire :

Fondation des Étoiles

Despite sex being an important basic human variable, publications often continue to neglect sex-based considerations and analyses in basic and clinical research. In the brain, sexual differentiation organizes the neural architecture differently between males and females, and the main influence on this process is exposure to gonadal steroids, such as testosterone and its metabolites, during sensitive periods in the perinatal development. Besides, significant sex differences have been shown in behaviour, stress responses, epilepsy and GABAergic network development. Therefore, we intend to understand how developmental sex differences underlie sexual dimorphism in brain inhibitory networks affecting stress responses and epileptogenesis.

To do so, we propose to study the implication of testosterone by using, on top of male and female animals, androgenised females as well as androgen-insensitive male rats. We will, in these contexts, study differences in hippocampal GABAergic network development and evaluate the impact of pre- and postnatal stress on epileptogenesis. The findings of this research, and others systematically studying both sexes, will certainly contribute to improved and accurate data used in the elaboration of clinical drugs affecting the GABAergic system in Canadian women, but also acknowledgement of the intricacies and differences between sexes by comprehending them fully.