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Plasticity of cardiac vagal motoneurons in response to remote ischemic preconditioning

Hornung, E., Robbins, S., Srivastava, A., Achanta, S., Schwaber, J., and Vadigepalli, R.


Poster # 76


The significance of the Dorsal Motor Nucleus of the Vagus (DMV) to the maintenance ofcardiac health was previously ambiguous and underappreciated and has only recentlybeen found to be profound (i.e. DMV activity is required for and sufficient to emulate thecardioprotection induced by physiological interventions, specifically remote ischemicpreconditioning (RIPC)). Due to the recency of this evidence, little is known of themolecular, anatomical, and functional basis for the key cardioprotective role of DMV.Findings emerging from our single cell and spatial transcriptomic methods combinedwith heart to brain neural tracing in 12 week old male and female Sprague Dawley ratshighlight pituitary adenylate cyclase-activating polypeptide (PACAP), as well as severalother functionally relevant transcripts, as markers specifically of cardiac-projecting DMVneurons. We have also found several transcripts, including PACAP, to beneuroanatomically DMV-specific relative to the surrounding brainstem tissue, supportingthe potential for DMV fiber-specific molecular identifiers innervating neurons of theintrinsic cardiac nervous system (ICN). Given the vast literature suggesting thecardioprotective effect of PACAP on ICN neurons, we hypothesize that RIPC increasesPACAP levels in DMV. Preliminary RT-qPCR data from DMV tissue micro punchessuggests differential expression of various neuromodulatory markers, includingupregulation of the neurotrophic and cardioprotective neuropeptide PACAP, in responseto RIPC. To build upon these preliminary RT-qPCR results, we have been collectingbrainstem samples post-RIPC and post-sham surgery in an effort to validate thesetranscriptomic findings at the protein level with immunofluorescence staining andimaging measuring expression levels of PACAP, and other neuromodulatory markers.This work fills a major gap in the understanding of the cellular mechanisms by whichparasympathetic drive provides cardioprotection and provides a future translational pathto emulating PACAP's vagal neuromodulatory effects on heart health.

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