Enhanced neuronal activation in central autonomic network nuclei in aged mice following acute peripheral immune challenge

Infection is associated with activation in central autonomic nuclei involved in mediating coordinated host defense responses. Aged mice showed exaggerated sickness behavior following peripheral injection of pro-inflammatory bacterial lipopolysaccharide (LPS), but is unknown whether central autonomic network responses are concomitantly increased. To assess whether aged mice exhibit enhanced neural response to LPS, we compared neural responses using c-Fos immunohistochemistry in aged BALB/c mice (22-24 months) with those of young adult peers (3-6 months). Intraperitoneal LPS challenge induced robust expression of c-Fos protein in central autonomic regions, including catecholaminergic neurons in the pons and brainstem, as well as in barrier-associated areas including the circumventricular organs. The numbers of c-Fos positive neurons were significantly greater in the aged compared to the young adult mice. These findings show age-associated enhancement of response to inflammation in the blood-brain chemosensory interfaces as well the central autonomic pathways involved in the elaboration of sickness symptoms, which may contribute to exaggerated sickness and poorer outcomes of infectious disease in the elderly.