Levels ofpros-methylimidazoleacetic acid: Correlation with severity of Parkinson's disease in CSF of patients and with the depletion of striatal dopamine and its metabolites in MPTP-treated mice
Autor: | George D. Prell, Albert M. Morrishow, R. S. Burns, Patrizio Blandina, Jai K. Khandelwal, Jack Peter Green |
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Rok vydání: | 1991 |
Předmět: |
Male
medicine.medical_specialty 3 4-Dihydroxyphenylacetic acid Parkinson's disease Dopamine Striatum Mice Norepinephrine chemistry.chemical_compound Cerebrospinal fluid Reference Values Internal medicine medicine Animals Humans Biological Psychiatry Aged Cerebral Cortex General Neuroscience MPTP Homovanillic acid Imidazoles Homovanillic Acid Parkinson Disease medicine.disease Corpus Striatum Mice Inbred C57BL Psychiatry and Mental health Endocrinology medicine.anatomical_structure Neurology chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Cerebral cortex 3 4-Dihydroxyphenylacetic Acid Female Neurology (clinical) Psychology medicine.drug |
Zdroj: | Journal of Neural Transmission - Parkinson's Disease and Dementia Section. 3:109-125 |
ISSN: | 1435-1463 0936-3076 |
DOI: | 10.1007/bf02260886 |
Popis: | The cerebrospinal fluid (CSF) levels of pros-methylimidazoleacetic acid (p-MIAA) in thirteen medication-free patients with mild to moderate Parkinson's disease were highly correlated (Spearman's rho = 0.749, p less than 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 (rho = 0.78, p less than 0.05 and rho = 1.0, p less than 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 less than 0.01), homovanillic acid (r = 0.79, p less than 0.02), 3,4-dihydroxyphenylacetic acid (r = 0.84, p less than 0.01) and norepinephrine (r = 0.91, p less than 0.002) in striatum, but not in cortex of the same mice. No such correlations were observed in either striatum or cortex of saline-treated 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. |
Databáze: | OpenAIRE |
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