Nigrostriatal Reduction of Aromatic L‐Amino Acid Decarboxylase Activity in MPTP‐Treated Squirrel Monkeys: In Vivo and In Vitro Investigations

Aromatic L‐amino acid decarboxylase (AAAD) activity was examined in vivo with positron emission tomography (PET) using 6‐[18F]fluoro‐L‐DOPA (FDOPA) in squirrel monkeys lesioned with graded doses of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In vitro biochemical determination...

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Bibliographic Details
Published in:	Journal of neurochemistry Vol. 74; no. 3; pp. 1147 - 1157
Main Authors:	Yee, R.E., Huang, S.‐C., Stout, D.B., Irwin, I., Shoghi‐Jadid, K., Togaski, D.M., DeLanney, L.E., Langston, J.W., Satyamurthy, N., Farahani, K.F., Phelps, M.E., Barrio, J.R.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Science Ltd 01-03-2000 Blackwell
Subjects:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine 6‐[18F]Fluoro‐L‐DOPA Animals Aromatic Amino Acid Decarboxylase Inhibitors Aromatic L‐amino acid decarboxylase Aromatic-L-Amino-Acid Decarboxylases - metabolism Biological and medical sciences Corpus Striatum - drug effects Corpus Striatum - enzymology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dihydroxyphenylalanine - analogs & derivatives Dopamine Agents - pharmacology Female Male Medical sciences Neurology Saimiri Saimiri sciureus Squirrel monkeys Substantia Nigra - drug effects Substantia Nigra - enzymology Tomography, Emission-Computed Animal model Nervous system diseases Enzyme Central nervous system Parkinson disease Lyases Saimiri sciureus Cerebral disorder Carbon-carbon lyases Vertebrata Mammalia Enzymatic activity Carboxy-lyases Animal Central nervous system disease Neurotoxin Primates Simioidea Aromatic-L-amino-acid decarboxylase Degenerative disease Nigrostriatal pathway Brain (vertebrata) Extrapyramidal syndrome
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Summary:	Aromatic L‐amino acid decarboxylase (AAAD) activity was examined in vivo with positron emission tomography (PET) using 6‐[18F]fluoro‐L‐DOPA (FDOPA) in squirrel monkeys lesioned with graded doses of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In vitro biochemical determinations of AAAD activity in caudate, putamen, substantia nigra, and nucleus accumbens were performed in the same animals to establish a direct comparison of in vivo and in vitro measurements. In vivo and in vitro AAAD activities in caudate/putamen were substantially reduced in animals treated with the highest dose of MPTP (2.0 mg/kg). The percent change in the striatal FDOPA uptake (Ki) and decarboxylation rate constant (k3) values resulting from MPTP treatment showed highly significant correlations with in vitro‐determined AAAD activities. However, decarboxylase rates within individual animals presented as ~ 10‐fold difference between in vivo and in vitro values. Lower in vivo k3 measurements may be attributed to several possibilities, including transport restrictions limiting substrate availability to AAAD within the neuron. In addition, reductions in AAAD activity in the substantia nigra did not parallel reductions in AAAD activity within the striatum, supporting the notion of a nonlinear relationship between nigrostriatal cell degeneration and terminal losses. This work further explores the role of AAAD in Parkinson's disease, a more important factor than previously thought.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0022-3042 1471-4159
DOI:	10.1046/j.1471-4159.2000.741147.x