Parkinson's disease: Studies on the pathology of the disease and the mechanism of action of the neurotoxin MPTP

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1988

OSTI ID:5647254

D'Amato, R J

In humans and animals, exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) causes certain clinical, pathological, and neurochemical features of Parkinson's disease (PD). MPTP is metabolized in the brain by monoamine oxidase (MAOb) to 1-methyl-4-phenylpyridine (MPP{sup +}), which is selectively accumulated and concentrated by high affinity uptake mechanisms into catecholamine neurons. We have demonstrated high affinity binding of MPP{sup +} to neuromelanin which may result in a toxic intraneuronal sequestration of MPP{sup +}. The involvement of neuromelanin is further supported by the demonstration that monkeys pretreated with chloroquine prior to the administration of MPTP are protected from MPTP induced neurotoxicity. Decreases in serotonin levels have been reported in the brains and spinal fluid of patients with both Parkinson's and Alzheimer's disease. In an effort to investigate the pathology of serotonin neurons in postmortem brain tissue from Parkinson's and Alzheimer's patients, ({sup 3}H)citalopram was characterized as a means of labeling serotonin uptake sites present on serotonin terminals.

• Research Organization: Johns Hopkins Univ., Baltimore, MD (USA)
• OSTI ID: 5647254
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL CELLS
ANIMALS
ANTIGENS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MONKEYS
NERVE CELLS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PRIMATES
PROTEINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RECEPTORS
SEROTONIN
SOMATIC CELLS
SYMPATHOMIMETICS
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES