Expression of catechol-O-methyltransferase in the brain and periphery of normal and MPTP-treated common marmosets

被引:6
作者
Zeng, Bai-Yun [1 ]
Balfour, Robert H. [1 ]
Jackson, Mike J. [1 ]
Rose, Sarah [1 ]
Jenner, Peter [1 ]
机构
[1] Kings Coll London, Neurodegenerat Dis Res Grp, Sch Biomed & Hlth Sci, London SE1 1UL, England
关键词
Catechol-O-methyltransferase; Brain; Common marmoset; PARKINSONS-DISEASE; L-DOPA; METHYL-TRANSFERASE; GENE-EXPRESSION; ENZYME-ACTIVITY; FRONTAL-CORTEX; RAT-BRAIN; PRIMATES; COMT; DYSKINESIA;
D O I
10.1007/s00702-009-0315-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Catechol-O-methyltransferase (COMT) inhibition is widely used to potentiate the effects of levodopa in Parkinson's disease but the effects of nigral dopaminergic cell loss and levodopa treatment on COMT activity are not known. The present study investigated the expression of COMT in the brain and liver of normal common marmosets, and animals treated with MPTP and those treated with levodopa to induce dyskinesia. Reverse transcript PCR demonstrated the expression of COMT mRNA in the liver, cortex and striatum of normal marmosets. Using Western blotting, the presence of two subunits of COMT protein, membrane bound COMT (MB-COMT) and soluble COMT (S-COMT), was shown in the liver, cortex and striatum of normal marmosets. Quantitative analysis of the MB-COMT and S-COMT subunit bands showed that there was no significant difference in the density of bands in MPTP treated marmosets or those exposed to levodopa compared to normal animals. COMT immunoreactivity was expressed in many brain regions including the cortex and striatum. No difference in COMT staining intensity was observed between normal, MPTP exposed or MPTP plus levodopa treated animals. COMT immunostaining was present in most striatal neurones and it was occasionally seen in glial cells. The data from present study demonstrated the expression of COMT mRNA and protein in the brain of common marmoset contrary to a previous report that it is not expressed in this species. COMT activity appears unaffected by loss of the dopaminergic nigro-striatal pathway and levodopa treatment.
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页码:45 / 51
页数:7
相关论文
共 36 条
[1]  
Akil M, 2003, J NEUROSCI, V23, P2008
[2]   Catechol-O-methyltransferase and its inhibitors in Parkinson's disease [J].
Bonifacio, Maria Joao ;
Palma, P. Nuno ;
Almeida, Luis ;
Soares-da-Silva, Patricio .
CNS DRUG REVIEWS, 2007, 13 (03) :352-379
[3]   PURIFICATION AND KINETIC-PROPERTIES OF LIVER MICROSOMAL-CATECHOL-O-METHYLTRANSFERASE [J].
BORCHARDT, RT ;
CHENG, CF ;
COOKE, PH ;
CREVELING, CR .
LIFE SCIENCES, 1974, 14 (06) :1089-1100
[4]  
Brooks David J, 2008, Neuropsychiatr Dis Treat, V4, P39
[5]   Chronic antipsychotics treatment regulates MAOA, MAOB and COMT gene expression in rat frontal cortex [J].
Chen, Mao-Liang ;
Chen, Chia-Hsiang .
JOURNAL OF PSYCHIATRIC RESEARCH, 2007, 41 (1-2) :57-62
[6]  
CHENG MC, 2007, INT J NEUROPSYCHOPH, V17, P1
[7]   Effects of catechol-O-methyltransferase inhibition on the rates of uptake and reversibility of 6-fluoro-L-dopa trapping in MPTP-induced parkinsonism in monkeys [J].
Doudet, DJ ;
Chan, GLY ;
Holden, JE ;
Morrison, KS ;
Wyatt, RJ ;
Ruth, TJ .
NEUROPHARMACOLOGY, 1997, 36 (03) :363-371
[8]   CATECHOLAMINE-METABOLIZING ENZYME-ACTIVITY IN THE NIGROSTRIATAL SYSTEM [J].
FRANCIS, A ;
WHITTEMORE, R ;
JEFFERY, DR ;
PEARCE, LB ;
ROTH, JA .
BIOCHEMICAL PHARMACOLOGY, 1987, 36 (13) :2229-2231
[9]   SOLUBLE AND PARTICULATE FORMS OF RAT CATECHOL-O-METHYLTRANSFERASE DISTINGUISHED BY GEL-ELECTROPHORESIS AND IMMUNE FIXATION [J].
GROSSMAN, MH ;
CREVELING, CR ;
RYBCZYNSKI, R ;
BRAVERMAN, M ;
ISERSKY, C ;
BREAKEFIELD, XO .
JOURNAL OF NEUROCHEMISTRY, 1985, 44 (02) :421-432
[10]  
GULDBERG HC, 1975, PHARMACOL REV, V27, P135