Tyrosine Hydroxylase-Expressing Neurons in the Vagal Ganglia: Characterization and Implications

Background/Objectives: A combination of sympathoexcitation and parasympathetic withdrawal contributes to the occurrence of ventricular arrhythmias, sudden cardiac death, and progression of heart failure after myocardial injury. As a result, vagal nerve stimulation has been under investigation as a potential option to increase cardiac vagal tone, but the results of clinical trials have been mixed. Prior studies have suggested that the vagal ganglia and nerves may contain sympathetic neurons that express tyrosine hydroxylase (TH), which, if stimulated, could potentially mitigate the effects of vagal nerve stimulation. The goal of the current study was to better characterize these neurons. Methods: Immunohistochemical staining was performed to evaluate for the presence of TH-expressing neurons in the inferior vagal (nodose) ganglia from six pigs. Additional staining was performed for dopamine beta-hydroxylase (DBH), which is required for the production of norepinephrine (NE), to determine if these neurons are indeed sympathetic and capable of releasing NE. Analysis of stellate ganglia was also performed, given that these ganglia are known to provide sympathetic innervation to the heart and release NE in the myocardium. Results: While nearly all TH-expressing neurons in the stellate ganglia expressed DBH, confirming that they can produce or release NE, none of the TH-expressing neurons in the vagal ganglia expressed DBH, demonstrating that these are dopaminergic but not noradrenergic neurons. Conclusions: TH-expressing neurons in the vagal ganglia previously reported to be potentially "sympathetic" do not express DBH and are, therefore, not capable of synthesizing NE.