Serveur d'exploration sur la maladie de Parkinson

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Markers of dopamine depletion and compensatory response in striatum and cerebrospinal fluid

Identifieur interne : 002312 ( Main/Exploration ); précédent : 002311; suivant : 002313

Markers of dopamine depletion and compensatory response in striatum and cerebrospinal fluid

Auteurs : A. Loeffler [États-Unis] ; A. Lewitt [États-Unis] ; J. Demaggio [États-Unis] ; L. Juneau [États-Unis] ; E. Milbury [États-Unis] ; R. Matson [États-Unis]

Source :

RBID : ISTEX:580E8356C3EC4678951DC05A1BD774683BB6EE3B

Abstract

Summary: Though depletion of CSF homovanillic acid (HVA) concentration has often been regarded as a direct indicator of dopamine (DA) deficiency in Parkinson's Disease (PD), CSF HVA is normal in mildly affected patients. To explore why, we measured DA and its metabolites in striatum and CSF in rabbits receiving reserpine for 5 days. Reserpine, which depletes striatal DA by disrupting vesicular storage of the neurotransmitter, results in a compensatory increase of DA turnover. In response to a 96% depletion of striatal DA, its catabolic intermediates 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) decreased 64% and 92% in striatum, although the endproduct, HVA, was unchanged. In contrast, CSF concentrations of HVA and DOPAC increased significantly, though 3-MT and levodopa (LD) were unaltered. A 5-fold rise in striatal LD concentration after reserpine-induced DA depletion provided evidence for enhanced DA synthesis. As in PD, the compensatory increase of DA synthesis after reserpine administration confounds the ability of CSF HVA to reflect DA depletion.

Url:
DOI: 10.1007/BF02252962


Affiliations:


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<div type="abstract" xml:lang="en">Summary: Though depletion of CSF homovanillic acid (HVA) concentration has often been regarded as a direct indicator of dopamine (DA) deficiency in Parkinson's Disease (PD), CSF HVA is normal in mildly affected patients. To explore why, we measured DA and its metabolites in striatum and CSF in rabbits receiving reserpine for 5 days. Reserpine, which depletes striatal DA by disrupting vesicular storage of the neurotransmitter, results in a compensatory increase of DA turnover. In response to a 96% depletion of striatal DA, its catabolic intermediates 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) decreased 64% and 92% in striatum, although the endproduct, HVA, was unchanged. In contrast, CSF concentrations of HVA and DOPAC increased significantly, though 3-MT and levodopa (LD) were unaltered. A 5-fold rise in striatal LD concentration after reserpine-induced DA depletion provided evidence for enhanced DA synthesis. As in PD, the compensatory increase of DA synthesis after reserpine administration confounds the ability of CSF HVA to reflect DA depletion.</div>
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