Susan Amara, Ph.D., Scientific Director NIMH

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Amphetamine regulation of signaling in DA neurons
Neurotransmitter transporters present at the cell surface are well-established as the primary targets for psychostimulant drugs of abuse and for drugs such as methylphenidate and amphetamines, which are used to treat attention deficit disorders. In recent studies, we have observed that once amphetamines enter neurons they can activate multiple intracellular signaling pathways...

Krystof Bankiewicz, M.D, Ph.D., Professor University of California San Francisco

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Gene therapy of catecholamine-related diseases
This lecture gives the background, recent progress, and plans for using gene transfer technology to treat catecholamine-related genetic diseases. Direct intraparenchymal injection of adeno-associated viral vectors as a locally administered treatment has great potential as a gene therapy method but requires accurate delivery to maximize safety and efficacy...

Graeme Eisenhofer, Ph.D., Professor University of Dresden Germany

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From catecholamine metabolism to metabolomics of adrenal disorders
By the mid-1980's much of the basic knowledge about catecholamines had been established through the work of different groups including that led by Irwin J. Kopin at the NIH. Joining that effort in 1985 it turned out that there remained unanswered questions concerning the relative contributions of different sources of catecholamines and the processes by which and places where catecholamine metabolites were produced...

David Goldstein, M.D, Ph.D., Senior Investigator NINDS

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Catecholamine autotoxicity
A variety of neurodegenerative diseases including Parkinson disease and dementia with Lewy bodies feature profound catecholamine depletion in the brain and heart and intra-neuronal deposition of the protein alpha-synuclein (AS) in Lewy bodies in the brain and sympathetic nervous system. What renders catecholamine neurons susceptible in these diseases, and what links catecholamine deficiency with Lewy bodies?...

Daniela Jezova, PharmDr., DrSc., Professor Slovak Academy of Sciences Slovakia

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Catecholamine responses to stressors
Sympathetic and cardiovascular activation in response to stress stimuli1 that occur frequently in daily life belongs to relevant risk factors for the development of stress-related adverse factors and diseases. Despite intensive research over many years, we still do not know exactly whether it is harmful or beneficial to react to acute stress stimuli with high rates of catecholamine release for the long-term outcome. The aim of this overview is to review our previously obtained data in subjects with stress-related pathological states from the perspective of the magnitude of catecholamine response to acute stressors...

Stephen Kaler, M.D., Senior Investigator NICHD

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Neurochemicals as biomarkers of treatment response in Menkes disease.
Dopamine-beta-hydroxylase (DBH) is a copper-dependent enzyme that relies on the copper transporter, ATP7A, to make this metal cofactor available to DBH apoenzyme in the secretory pathway of dopaminergic cells. DBH normally converts dopamine (DA) to norepinephrine (NE), and biallelic mutations in the DBH gene cause derangement of neurochemical levels in blood and cerebrospinal fluid and a clinical syndrome of dysautonomia. Similar neurochemical derangements are evident in Menkes disease, a distinctive X-linked recessive disorder of copper metabolism caused by ATP7A mutations, and a serious illness for which we are testing experimental therapeutics, including viral gene therapy...

Karel Pacak. D.Sc., M.D., Ph.D., Senior Investigator

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A new paraganglioma-duodenal somatostatinoma-polycythemia syndrome
Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, erythropoiesis, and development. Paragangliomas/pheochromocytomas are catecholamine-producing tumors. The occurrence of two or more distinct types of tumors - one of them paraganglioma - is unusual in a patient, except in hereditary cancer syndromes. Polycythemia, in which the proportion of blood volume occupied by red cells and the red-cell mass are elevated, can be secondary (mediated by circulating erythropoietin) or primary and can be related to abnormalities in hypoxia-sensing pathways...

Nora Volkow, M.D., Director NIDA

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Dopamine and Drug Abuse
Addiction is a disorder that involves complex interactions between genes, development, and the social environment. Studies employing neuroimaging technology paired with behavioral measurements, and more recently genetics, have led to remarkable progress in elucidating neurochemical and functional changes that occur in the brains of addicted subjects. Although large and rapid increases in dopamine have been linked with the rewarding properties of drugs, the addicted state, in striking contrast, is marked by significant decreases in brain dopamine D2 receptor mediated signaling...

Moussa Youdim, Ph.D., Professor Emeritus Rappaport Institute Israel

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Multi-target neuroprotective and neurorestorative drugs
In Parkinson's disease (PD) and Alzheimer's disease (AD) no drugs are available to prevent the neuronal cell loss, and drugs in the clinic have at best symptomatic activity. In both diseases the patients have predisposition to depressive illness, and a significant percentage of PD patients have frontal cortex dementia. Due to the complex etiology of the diseases no ''magic bullet'' is available to prevent the various cascades of neurotoxic events resulting in neurodegeneration...

Michael Ziegler, M.D., Professor University of California San Diego

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Catecholaminergic changes after prolonged space flight
In 1977 Ziegler, Lake and Kopin reported that severe orthostatic hypotension (OH) could be caused by central or peripheral nerve defects that could be distinguished using the plasma norepinephrine (NE) response to standing...
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