ISSN:
1435-1463
Keywords:
Parkinson's disease
;
pros-methylimidazoleacetic acid
;
MPTP
;
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
;
dopamine
;
dopamine metabolites
;
homovanillic acid
;
DOPAC
;
norepinephrine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The cerebrospinal fluid (CSF) levels ofpros-methylimidazoleacetic acid (p-MIAA) in thirteen medication-free patients with mild to moderate Parkinson's disease were highly correlated (Spearman's ρ=0.749, p〈0.005) with the severity of signs of the disease as scored on the Columbia University Rating Scale. Levels of p-MIAA in males (n=8) and females (n=5) were each significantly correlated with scores of severity (ρ=0.78, p〈0.05 and ρ=1.0, p〈0.05, respectively). In C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP), levels of p-MIAA were significantly correlated with the depleted levels of dopamine (r=0.85, p〈0.01), homovanillic acid (r=0.79, p〈0.02), 3,4-dihydroxyphenylacetic acid (r=0.84, p〈0.01) and norepinephrine (r=0.91, p〈0.002) in striatum, but not in cortex of the same mice. No such correlations were observed in either striatum or cortex of salinetreated control mice. Mean levels of p-MIAA in CSF did not differ significantly between patients and age-matched controls; and mean levels of p-MIAA in striatum did not differ between MPTP-treated mice and controls. The simplest hypothesis to account for these strong correlations in the absence of differences in mean levels of p-MIAA is that accumulation of p-MIAA [or process(es) that govern its accumulation] influences a failing nigrostriatal system. It is also possible (in analogy with findings in other diseases and with other drugs) that measurements of the putative metabolite(s) of p-MIAA may distinguish the patients and the MPTP-treated mice from their respective controls. Elucidation of the processes that regulate formation and disposition of p-MIAA in brain and information on the neural effects of p-MIAA, its precursors and its putative metabolites may yield insight into factors that regulate the progression of Parkinson's disease, and may shed additional light on the cause(s) of this disease.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02260886
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