Anorexia induces a microglial associated pro-inflammatory environment and correlates with neurodegeneration in the prefrontal cortex of young female rats

Abstract

Dehydration-Induced Anorexia (DIA) is a murine model that reproduces weight loss and avoidance of food, despite its availability. The prefrontal cortex (PFC) integrates sensory inputs and updates associative learning to promote (hunger) or inhibit (satiety) food-seeking behavior. In this study we tested if anorexia induces a pro-inflammatory environment associated with microglia in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), specific subregions of the PFC involved in appetite. Our results showed that anorexia increased microglial density, promoted a de-ramified morphology and augmented the de-ramified/ramified ratio in the mPFC and OFC but not in the motor cortex. Anorexia also increased the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. This pro-inflammatory environment associated with microglia activation correlates with neuronal damage as revealed by Fluoro Jade C (FJC) and NeuN immunolabeling. We conclude that anorexia triggers a pro-inflammatory environment associated with microglia that correlates with neurodegeneration in the mPFC and OFC.