Descripción del proyecto
Dilucidar la neurobiología de los atracones provocados por el estrés
Los trastornos de la conducta alimentaria y la obesidad amenazan la salud de diversas maneras. El trastorno de sobreingesta compulsiva se ha relacionado con alteraciones de los circuitos neuronales, pero es necesario seguir investigando a fin de encontrar opciones de tratamiento eficaces para esta enfermedad. El proyecto ReCoDE, financiado con fondos europeos, se centrará en el modo en que el estrés altera la fuerza de las conexiones en el encéfalo que intervienen en la toma de decisiones y cómo puede desencadenar un comportamiento alimentario impulsivo. Además, buscará formas de remodelar este proceso mediante la manipulación específica de la actividad encefálica. Se utilizará electrofisiología, optogenética y rastreo neuronal para revelar si los atracones se producen debido a cambios en el control de la corteza prefrontal sobre los circuitos laterales del hipotálamo que regulan la ingesta de alimentos. Los resultados pueden ser prometedores para futuros tratamientos de los trastornos alimentarios.
Objetivo
Obesity and eating disorders are critical problems in society. Many patients with these brain diseases cope with stress by ravenous food intake (binge eating), which engenders new stress and maintains the pathology. Evidence-based treatments for this are urgently needed, but their implementation is hindered by a knowledge gap on: (i) which stress-driven neural disruptions cause binge eating, and (ii) whether these neural circuit changes can be normalized for therapeutic gain.
Studies in humans and rodents link binge eating to dysfunction of the prefrontal cortex (PFC), a brain region orchestrating the stress response. However, it is unknown how effects of stress on PFC output cause binge eating. The PFC prominently innervates the lateral hypothalamus (LHA), a region with a crucial role in managing food intake, yet little is known about the function of PFC regulation of the LHA. I predict that stress-induced binge eating requires a functional reorganization of prefrontal cortical control over lateral hypothalamus feeding circuits, and that this control can be restored to limit binge eating.
I propose a cutting-edge threefold strategy to address these hypotheses in mouse models:
1. I will unravel the make-up of PFC-LHA circuitry, combining electrophysiology, optogenetics and neural tracing. I will assess how stress functionally alters this complex network.
2. I will determine the concurrent activity at multiple sites within PFC-LHA circuitry as mice engage in stress-driven binge eating, using fiber photometric calcium recordings.
3. I will assess if normalizing stress-altered PFC-LHA synapses rebalances this circuitry in vivo and limits binge eating. For this I will combine optogenetic plasticity protocols, with fiber photometric measurements in freely moving mice.
Overall, this challenging project aims to unravel the unclear neurobiology of stress-induced binge eating. If successful, this would provide a key advance in understanding binge eating pathologies.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
3584 CX Utrecht
Países Bajos