Compared with their littermate controls, Mlc1-ErbB2V664E mice consumed much less food and water after Dox withdrawal. Twenty days after Dox withdrawal, they exhibited malnourishment with significantly smaller body sizes and lighter weights (Figure 5a and b). To explore whether there was a peripheral problem causing anorexia, we dissected their digestive systems and discovered atrophy of the gastrointestinal tract and accessory organs (Figure 5c). Further investigation of gastrointestinal tract sections with hematoxylin and eosin (H & E) staining showed no pathological changes, although the stomachs were constricted because of lack of content (Figure 5d). There were no cells targeted by Mlc1-tTA in the gastrointestinal tract of Mlc1-ErbB2V664E mice (Supplementary Figure S11a and b). Therefore, anorexia was caused by an inhibition of neural circuits for feeding behavior. Remarkably, hypothalamic astrocytes have crucial roles in controlling feeding behavior , and hypothalamic inflammation is linked to anorexia . Indeed, astrocytic ErbB activation induced prevalent astrogliosis and associated inflammation in the brain including the hypothalamus, as indicated by intensively stained GFAP+ and Iba1+ cells there (Figure 5e). To screen for other possible pathological changes, mouse brains were sectioned for H & E staining. Astrocyte dysfunction and associated inflammation would disrupt the integrity of the brain–blood barrier and influence cerebrospinal fluid production . As a result, the ventricles of Mlc1-ErbB2V664E mice were larger than those of littermate controls. Nevertheless, other brain regions exhibited comparable sizes in the two groups (Figure 5f). Therefore, in animals with reactive astrogliosis and associated inflammation throughout the brain, anorexia was the predominant result, suggesting hypothalamic susceptibility.