Vulnérabilité et différences liées au sexe face aux troubles cognitifs post- traumatiques dans un modèle murin de traumatisme cérébral
Amandine Consumi
“Early activity in the developing brain” team

Abstract:
Traumatic Brain Injury (TBI) affects several million people each year around the world (Bondi et al., 2015). In 2020, according to the World Health Organization (WHO), TBI became the third leading cause of long-term mortality and disability, making it a major public health issue. It is known as a “silent epidemic” with a dynamic profile divided into 2 phases: an initial phase involving direct impact damage such as diffuse axonal lesions, edema or hemorrhage causing cellular and molecular upheavals; and a latent phase, consequence of these upheavals and seat of the appearance of various post-traumatic disorders such as motor, neurological, cognitive and neuropsychiatric impairments (Goubert, 2019; Tessier, 2023). Cognitive and neuropsychiatric disorders are the most common pathologies after TBI. However, these clinical presentations differ between men and women, which makes their management particularly difficult.
On the neurobiological level, pre-clinical studies carried out on the matter highlight alterations of hippocampal neurogenesis as well as of the chloride homeostasis dependent GABAergic neurotransmission. Nevertheless, almost all studies on the subject were conducted exclusively in males. These elements invite us to ask ourselves: are sex-related differences involved in TBI sequalae?
My thesis work suggests that there are sex-related differences in the molecular, cellular and behavioral responses following TBI and suggest a differential strategy in females to compensate for trauma-induced neuronal deficits. Indeed, I was able to highlight distinct behaviors between males, that exhibit responses associated with anxiety symptoms and females expressing impulsiveness related symptoms. At the cellular and molecular level, I found that although both sexes have a loss of parvalbumin interneurons in the hippocampus 1 month after the trauma, it seems that females are more vulnerable to these disruptions. This is confirmed by the high expression of pro-apoptotic factor P75NTR in females and neurotrophic factor BDNF in males. Furthermore, my results show an alteration of theta rhythms in the hippocampus of injured animals associated with a decrease in cognitive performance and again emphasize the complexity of traumatic sequelae in females who present a stronger variability of these hippocampal rhythms.

Jury:
Isabelle BARDOU, Rapportrice – Université de Caen
Gilles HUBERFELD, Rapporteur – Institut de Psychiatrie et Neuroscience de Paris (IPNP)
Caroline CHAMBON, Examinatrice – amU
Isabelle GUILLEMAIN, Examinatrice – Grenoble université
Valery MATARAZZO, Président – amU
Christophe PELLEGRINO, Directeur de thèse – amU
Claudio RIVERA, Co-directeur de thèse – amU

Monday, April 28, 2025, 10am, Inmed conference room