Donald B. Hoover, Ph.D.
Key Laboratory Personnel:
Anthony Jackson, B.S., Lab Coordinator
Hunter Pearson, Graduate Student
Education and Professional Background:
Dr. Hoover received a B.S. in chemistry from Grove City College in 1972 and a Ph.D. in pharmacology from West Virginia University in 1972. He was awarded a Pharmacology Research Associate Training Program Fellowship in 1976 from the National Institutes of Health where he spent two years training as a Staff Fellow in the neuropharmacology and histopharmacology laboratory of Dr. David Jacobowitz. Dr. Hoover joined the pharmacology faculty at ETSU in 1978. He has been active in grant review for the American Heart Association and currently serves on their Molecular Signaling Peer Review Committee. Dr. Hoover received the ETSU Distinguished Faculty Award in Research for 2002.
• Structure and function of neurons that control cardiac function
• Development of cardiac parasympathetic and sympathetic neurons
• Structural and functional remodeling of cardiac innervation in heart disease
My laboratory has a long-term interest in the neural mechanisms that control cardiac function. Much of our work has focused on defining the neurochemical anatomy and neuropharmacology of the heart. We are particularly interested in learning the roles that novel neurotransmitters (e.g., neuropeptides) have in regulating neurotransmission at the intrinsic cardiac ganglia and in modulating cardiac function directly. More recently our interests have expanded to include the remodeling of cardiac neurons and nerve fibers in disease states (e.g., diabetes and heart failure) and learning the impact that these changes have in cardiac pathogenesis. As an outgrowth of this new research direction, my laboratory has embarked on studies aimed at learning the roles of neurotrophic factors and neuropoietic cytokines in the development and remodeling of cardiac ganglia and innervation of the heart (Fig. 1). This research employs a wide range of experimental techniques including molecular biology, immunohistochemistry, cell culture (Fig. 2), cellular electrophysiology, in vivo and in vitro monitoring of cardiac function, and classical concentration-response analysis.
Figure 1. Diagram illustrating the basic organization of parasympathetic and sympathetic neurons that innervate the heart and the opposing effects of their neurotransmitters on cardiac function. Postganglionic sympathetic neurons have somata in the stellate ganglia, which are located near the spinal cord. Many noradrenergic neurons in these ganglia have long axonal projections to the heart. In marked contrast, postganglionic parasympathetic neurons that innervate the heart are localized to cardiac ganglia, and cholinergic neurons in these ganglia have much shorter axonal projections to reach their cardiac targets. The primary targets of cholinergic nerves in the mouse heart are the sinoatrial node (i.e., pacemaker), the atrioventricular node, atrial muscle, and the cardiac conducting system.
Figure 2. Fluorescence images demonstrating effect of nerve growth factor (NGF) to stimulate neurite outgrowth from adult mouse stellate ganglion. The stellate ganglion was removed and cut into fragments, which were placed on collagen gels impregnated with 100 ng NGF/mL gel. These fragments were maintained in culture for 4 days at 37C. The preparations were fixed and immunostained for a neuronal marker.
AHA (Hoover, Principle investigator)
Title: Neurotrophic factors mediate structural and functional remodeling of cardiac cholinergic neurons
NIH RO1 HL071830 (Hoover, co-investigator)
Title: Myocardial ischemia remodels the cardiac nervous system.
Hoover DB, Ganote CE, Ferguson SM, Blakely RD and Parsons RL. Localization of cholinergic innervation in guinea pig heart by immunohistochemistry for high-affinity choline transporters. Cardiovasc Res 62: 112-121, 2004.
Chang Y, Lawson LJ, Hancock JC and Hoover DB. Pituitary adenylate cyclase-activating polypeptide: localization and differential influence on isolated hearts from rats and guinea pigs. Regul Pept 129: 139-146, 2005.
Mabe AM, Hoard JL, Duffourc MM and Hoover DB. Localization of cholinergic innervation and neurturin receptors in adult mouse heart and expression of the neurturin gene. Cell Tissue Res 326: 57-67, 2006.
Hoard JL, Hoover DB and Wondergem R. Phenotypic properties of adult mouse intrinsic cardiac neurons maintained in culture. Am J Physiol Cell Physiol 273: C1875-C1883, 2007.
Tompkins JD, Ardell JL, Hoover DB and Parsons RL. Neurally-released pituitary adenylate cyclase-activating polypeptide (PACAP) enhances guinea pig intrinsic cardiac neurone excitability. J Physiol 582.1: 87-93, 2007.
Hoard JL, Hoover DB, Mabe AM, Blakely RD, Feng N and Paolocci N. Cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes, norepinephrine transporters, and the neurotrophin receptors tropomyosin-related kinase A and p75. Neuroscience 156: 129-142, 2008.
Hoover DB, Shepherd AV, Southerland EM, Armour JA and Ardell JL. Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium. Auton Neurosci 141: 38-45, 2008.
Hoover DB, Isaacs ER, Jacques F, Hoard JL, Page P and Armour JA. Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia. Neuroscience 164: 1170-1179, 2009.
Hoover DB, Tompkins JD and Parsons RL. Differential activation of guinea pig intrinsic cardiac neurons by the PAC1 agonists maxadilan and pituitary adenylate cyclase-activating polypeptide 27 (PACAP27). J Pharmacol Exp Ther 331: 197-203, 2009.
Mabe AM and Hoover DB. Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice. Cardiovasc Res 82: 93-99, 2009.