The autonomic nervous system (ANS) coordinates the body’s response to stress. Pro-inflammatory cytokines (e.g., tumor necrosis factor alpha, TNFα), released in response to different stressors, may influence underlying pathophysiology involving autonomic dysfunction. The current study evaluated the impact of peripheral TNFα on cellular activation in brainstem nuclei associated with autonomic function, including the dorsal vagal complex (DVC) and the ventral lateral medulla (VLM). Mice received a single intraperitoneal injection of TNFα and were processed two hours later to identify immunoreactive c-Fos in brainstem nuclei as a measure of cellular activity. The number of c-Fos immunoreactive cells increased after TNFα challenge within the DVC and VLM. Cell immunoreactive for c-Fos were concentrated lateral to the area postrema (AP), a circumventricular organ medial to the subdivision of the caudal portion of the nucleus of the solitary tract (cNTS) within the DVC. To examine the role of microglia in mediating cellular responses to peripheral TNFα, minocycline was administered into the fourth ventricle to decrease microglial function. Minocycline treatment reduced IBA-1 immunoreactivity in the AP and cNTS. When animals were challenged with TNFα after receiving minocycline, fewer c-Fos-positive cells were induced in the DVC and selectively in the rostral VLM. These findings highlight the spatial selectivity of cells in the brainstem to increased peripheral pro-inflammatory signaling, as well as the impact of resident microglia on autonomic circuitry responses.
Castellanos et al. (Mon,) studied this question.