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Autonomic Disorders

Program Duration: 2–5 years

18F-Dopamine heart and 18F-DOPA brain scans in a healthy volunteer (left) and a patient with Parkinson disease (right).



This program trains Fellows in patient-oriented, preclinical, and translational research about disorders of the autonomic nervous system. Because of the myriad roles of the autonomic nervous system in homeostasis, drug effects, and multi-disciplinary acute and chronic disorders of regulation, autonomic medical research requires thinking in terms integrative physiological concepts such as negative feedback and anticipatory regulation, multiple effectors and effector sharing, allostasis and allostatic load, and catecholaminergic neurodegeneration induced by positive feedback loops. The clinical research consists of developing and testing diagnostic and pathophysiologic biomarkers, natural history studies, and pathophysiologically relevant therapeutic interventions. Major emphasis is on autonomic failure in Parkinson’s disease (PD), dementia with Lewy bodies, pure autonomic failure, and other synucleinopathies evaluated by physiological, neurochechemical, Neuroimaging, microscopic, and genetic approaches. The preclinical research focuses on auto toxicity exerted by the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), harmful DOPAL-induced modifications of intracellular proteins such as alpha-synuclein, and strategies to mitigate those modifications. The program uses a variety of clinical assessment techniques to mitigate those modifications. The program uses a variety of clinical assessment techniques such as physiological autonomic function testing, catecholamine neurochemistry, and visualization of catecholaminergic innervation by positron emission tomography (PET) scanning, and immunofluorescence confocal microscopy. 

Area of Current Research

Diagnostic biomarkers and mechanisms of loss of catecholaminergic neurons in the brain and periphery
   in PD and related disorders
Relationships of autonomic failure to non-motor and pre-motor aspects of Lewy body diseases
Clinical laboratory evaluation and natural history of orthostatic hypotension
Experimental therapeutics targeting DOPAL formation and DOPAL-induced protein modifications
Collaborative clinical and preclinical studies of autonomic rare diseases
Computer modeling of cardiac sympathetic functions and mechanisms of noroadrenergic deficiency
Experimental therapeutics of neurogeneic orthostatic hypotension
 Clinical autonomic function testing
 Collaborative clinical and preclinical studies of catecholamine systems

Faculty

David S. Goldstein, M.D., Ph.D., Chief, Clinical Neurocardiology Section, goldsteind@ninds.nih.gov