Facteur neurotrophique dérivé du cerveau comme biomarqueur diagnostique et pronostique dans l'anorexie mentale

Anorexia nervosa (AN) is a multifaceted eating disorder marked by severe caloric restriction, extreme weight loss, and distorted body image. This thesis investigates the role of brain-derived neurotrophic factor (BDNF) in AN through the lens of neurobiological, metabolic, and psychological factors. Using a chronic animal model, the research examines how BDNF signaling intersects with reward and cognitive circuits, as well as its implications for the muscle-brain axis and the role of other neurotrophins in AN. Chapter 1 delves into the neurobiological and metabolic dimensions of AN. It focuses on how BDNF signaling dynamics are affected by chronic restriction, refeeding, and binge behaviors, specifically within brain structures associated with reward and cognitive circuits. Utilizing a chronic animal model, this chapter explores alterations in BDNF signaling across key brain regions, including the dorsal striatum (DS), prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA). It examines how these changes impact reward processing, cognitive functions, and overall metabolic homeostasis in the context of AN. The chapter also addresses the broader implications of these findings for understanding the neurobiological underpinnings of the disorder and its treatment. Chapter 2 investigates the dynamics of BDNF signaling and its relationship with genes implicated in the muscle-brain axis. This chapter examines how BDNF interacts with both rapid and slow muscle fibers and explores the connections between muscle and key brain regions, including the hippocampus and hypothalamus. The research highlights how these interactions influence neurobiological and metabolic processes in AN. By elucidating the role of BDNF in muscle-brain communication, this chapter contributes to a deeper understanding of the physiological mechanisms underlying AN and their potential implications for treatment strategies. Chapter 3 explores the role of other neurotrophins, specifically NTF3, NTF5, and NGF, in brain regions associated with AN. This chapter investigates how these neurotrophins are regulated and their impact on AN-related brain structures. By examining the expression and function of NTF3, NTF5, and NGF, the research provides insights into their contributions to the neurobiological processes underlying AN.