Fig. 13

Hypothetical model of the role of microglia in protection against the anorectic effects of DON. Under resting conditions, activated microglial cell populations located at the AP and AP/NTS interface, i.e., the funiculus separans, protect the brainstem parenchyma from hazardous molecules coming from the blood. These activated microglia populations may endocyte/phagocytize neurotoxic blood-derived molecules to maintain the parenchymal microenvironment around the CVO. After its administration, DON reaches the AP and diffuses into surrounding structures through fenestrated capillaries. The DON-induced modification of the microglial phenotype could facilitate its action on neuronal networks, responsible for the control of food intake, and located in the NTS. When microglia are deleted by PLX3397 or inhibited by minocycline, the DON diffusion from the AP is unrestricted, leading to an exacerbation of its action