Activation of PACAP+ vagal motoneurons following remote ischemic pre-conditioning

Abstract

The Dorsal Motor Nucleus of the Vagus nerve (DMV) provides parasympathetic innervation of the intrinsic cardiac nervous system (ICN), and it has been shown that DMV activity is required for the cardioprotection induced by remote ischemic pre-conditioning (RIPC) against the pathological effects of myocardial infarction. However, the mechanism behind the DMV’s cardioprotective effects is not well understood. Previous literature has shown that the DMV and the other vagal motor nuclei, the nucleus ambiguus (NA), innervate distinct cells within the ICN. DMV neurons project to many other organs in addition to the heart. The cardioprotective neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) has been found to be expressed in the fibers innervating the ICN, where it is co-localized with the parasympathetic marker, ChAT. While we have found PACAP to be expressed in cardiac-projecting DMV neurons, it is unknown whether these neurons are preferentially activated in response to RIPC. To assess the activity of these neurons following RIPC, we performed immunofluorescence staining of brainstem tissue containing DMV neurons for both PACAP, and c-FOS, a neuronal activity-dependent marker. We hypothesized that PACAP+ DMV neurons would have increased activity following RIPC, and therefore increased c-FOS intensity and increased co-localization with PACAP compared to sham control. Our results suggest that PACAP+ neurons in the DMV show increased activity following RIPC compared to sham, as defined by increased c-FOS fluorescence intensity and co-localization with PACAP. These results suggest that PACAP+ neurons are activated during the cardioprotective response to remote ischemic pre-conditioning. Funding was provided by the R01 HL161696 grant through National Heart, Lung, and Blood institute and the National Institutes of Health Common Fund SPARC Program Grant OT2OD030534. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.