Donald B. Hoover, Ph.D.
Department of Biomedical Sciences
PO Box 70577
East Tennessee State University
Johnson City, TN 37614-1708
Education and Professional Background:
1972 - B.S. in Chemistry, Grove City College, Grove City, PA
1976 – Ph.D. in Pharmacology, West Virginia University, Morgantown, WV
1976‑1978: Staff Fellow, National Institutes of Health, Bethesda, MD. Appointment through the Pharmacology Research Associate Program of the National Institute of General Medical Sciences. Preceptor‑Dr. David M. Jacobowitz, National Institute of Mental Health, Laboratory of Clinical Science, Section on Histopharmacology
1993: Visiting Scientist at Geisinger Clinic, Weis Center for Research, Danville, PA (Dr. Kenneth Baker's lab)
2011-present : Adjunct Professor, Department of Biological Sciences, East Tennessee State University, Johnson City, TN
Rolf Fritz, Laboratory Coordination (Director of confocal microscopy facility)
Anthony Downs, Research Technician
• Cardiovascular neuroscience and pharmacology (research and teaching)
• Neuroimmunology of the peripheral nervous system (research)
• Pharmacology of infectious diseases (teaching)
Research in my laboratory focuses on two major areas: 1) neural regulation of cardiac function (neurocardiology) and 2) neural regulation of immune cell function (peripheral neuroimmunology).
Neurocardiology Projects: Our research in this field has the primary goals of understanding the neurochemical anatomy and connectivity of the peripheral neurons that are responsible for rapid and precise regulation of cardiac function under physiological and pathophysiological conditions. Classically, this system contains sympathetic ganglia/neurons that supply noradrenergic innervation to the heart and intrinsic cardiac ganglia/neurons that supply cholinergic parasympathetic innervation. Both types of ganglia receive the classical preganglionic cholinergic input.
However, our research has demonstrated that neurons within these ganglia, receive a wide variety of additional inputs from chemically and functionally distinct neurons. Our neurocardiology experiments use a variety of techniques including immunohistochemistry, electrophysiology, organotypic and cell culture, and pharmacological studies of isolated atria and hearts. Ongoing projects are investigating the remodeling of sympathetic ganglia in association with ventricular tachycardia and the role of neurotrophic factors (e.g., neurturin) and sympathetic/parasympathetic interactions in the development of the intrinsic cardiac nervous system.
CGRP and SP are colocalized in varicose nerve fibers that surround ChAT-immunoreactive cholinergic neurons of human intrinsic cardiac ganglia. A-D: Confocal images of a section that was triple labeled to show ChAT (A, green), CGRP (B, blue), and SP (C, red). A: ChAT was localized to neurons and nerve fibers. B and C: CGRP (B) and SP (C) occurred only in varicose nerve fibers that often surrounded intrinsic cardiac neurons. D: Overlay of images A-C shows that SP was predominantly colocalized with CGRP (lavender). Some varicose nerve fibers contained CGRP alone (blue). Neither CGRP nor SP occurred in ChAT-positive cholinergic nerve fibers. All panels contain maximum projection images compiled from confocal scans that spanned 8 mm. Scale bar indicates 150 mm. From Neuroscience 164: 1170-1179, 2009.
Neuroimmunology Project: The systemic hyper-inflammatory response that develops during sepsis can cause short- and long-term morbidity as well as mortality. Our laboratory and others are investigating the cholinergic anti-inflammatory pathway to identify therapeutic targets for reducing the morbidity and mortality of sepsis. This pathway is part of a reflex arc that modulates immune responses by acting at the spleen to suppress production of pro-inflammatory cytokines. Neural components of the pathway comprise preganglionic vagal efferent nerves (cholinergic) and their target postganglionic sympathetic neurons (noradrenergic) that innervate the spleen. Recent evidence suggests that norepinephrine (released from sympathetic nerves in the spleen) activates a cholinergic phenotype in splenic T cells. The acetylcholine released from these cells is thought to suppress production of inflammatory cytokines by stimulating alpha7 receptors on macrophages. We are investigating the in situ expression of cholinergic markers and alpha7 receptors by immune cells in the spleen, circulation, and several organs before and during experimental sepsis. Additionally, our studies will evaluate the efficacy of GTS-21 (an alpha7 agonist) at preventing, attenuating, or reversing sepsis-induced cardiac dysfunction, pulmonary pathology, and immunosuppression.
Active Research Support:
2013-2015 American Heart Association, Greater Southeast Affiliate, “Cholinergic Anti-inflammatory Response to Vagal Stimulation in Polymicrobial Sepsis”, Donald B. Hoover, PI.
2010-2015 National Heart Blood and Lung Institute; R01 HL071830 (competing renewal), “Myocardial Ischemia Remodels the Cardiac Nervous System”, Donald B. Hoover, CI; Jeffrey L. Ardell, PI.
2011-2014 National Science Foundation, “REU Site: Undergraduate Research in Integrative Developmental Biology”, Donald B. Hoover, Senior personnel; Rebecca Pyles, PI.
Hancock, J.C. and Hoover, D.B. Capsaicin-evoked bradycardia in anesthetized guinea pigs is mediated by endogenous tachykinins. Regl. Pept. 147: 19-24, 2008.
Hoover, D.B., Shepherd, A.V., Southerland, E.M., Armour, J.A. and Ardell, J.L. Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium. Autonom. Neurosci. 141: 38-45, 2008.
Hoard, J.L., Hoover, D.B., Mabe, A.M., Blakely, R.D., Feng, N. and Paolocci, N. Cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes, norepinephrine transporters, and the neurotrophin receptors TrkA and p75. Neuroscience 156: 129-142, 2008.
Mabe, A.M. and Hoover, D.B. Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice. Cardiovasc. Res. 82: 93-99, 2009.
Hoover, D.B., Isaacs, E.R., Jacques, F., Hoard, J.L., Pagé, P. and Armour, J.A. Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia.Neuroscience 164: 1170-1179, 2009.
Hoover, D.B ., Tompkins, J.D. and Parsons, R.L. Differential activation of guinea pig intrinsic cardiac neurons by the PAC1 agonists maxadilan and pituitary adenylate cyclase-activating polypeptide 27 (PACAP27). J. Pharmacol. Exp. Therap. 331: 197-203, 2009.
Mabe, A.M. and Hoover, D.B. Remodeling of cardiac cholinergic innervation and control of heart rate in mice with streptozotocin-induced diabetes. Autonomic Neurosci. 162: 24-31, 2011.
Gibbons, D.D., Southerland, E.M., Hoover, D.B., Beaumont, E., Armour, J.A. and Ardell, J.L. Neuromodulation targets intrinsic cardiac neurons to attentuate neuronally-mediated atrial arrhythmias. Am. J. Physiol. Regul. Integr. Comp. Physiol. 302: R357-R364, 2011.
Fregoso, S.P. and Hoover, D.B. Development of cardiac parasympathetic neurons, glial cells, and regional cholinergic innervation of the mouse heart. Neuroscience 221: 28-36, 2012.
Hoover, D.B., Girard, B.M., Hoover, J.L. and Parsons, R.L. PAC1 receptors mediate positive chronotropic responses to PACAP-27 and VIP in isolated mouse atria. European Journal of Pharmacology 713: 25-30, 2013.
Burt, R., Graves, B.M., Gao, M., Li, C., Williams, D.L., Fregoso, S.P., Hoover, D.B., Li, Y., Wright, G.L. and Wondergem. R. 9-Phenanthrol and flufenamic acid inhibit calcium oscillations in HL-1 mouse cardiomyocytes. Cell Calcium 54: 193-201, 2013.
Li, L., Hatcher, J.T., Hoover, D.B., Gu, H., Wurster, R.D. and Cheng, Z.J. Distribution and morphology of calcitonin gene-related peptide and substance P immunoreactive axons in the whole-mount atria of mice. Auton Neurosci. 181:37-48, 2014.
Downs, A.M., Bond, C.E., and Hoover, D.B
. Localization of α7 nicotinic acetylcholine receptor mRNA and protein within the cholinergic anti-inflammatory pathway. Neuroscience. 266:178-185, 2014.
Hoover, J.L., Bond, C.E., Hoover, D.B. and Defoe, D.M. Effect of neurturin deficiency on cholinergic and catecholaminergic innervation of the murine eye. Exp Eye Res. 2014 Mar 19;122C:32-39. doi: 10.1016/j.exer.2014.03.002. [Epub ahead of print].
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