The novel cyclooxygenase-2 inhibitor GW637185X protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity

被引：8

作者：

Aguirre, Jose A. ^{[1
]}

Leo, Giuseppina ^{[3
]}

Cueto, Raquel ^{[2
]}

Andbjer, Beth ^{[4
]}

Naylor, Alan ^{[5
]}

Medhurst, Andrew D. ^{[5
]}

Agnati, Luigi F. ^{[3
]}

Fuxe, Kjell ^{[4
]}

机构：

[1] Univ Malaga, Sch Med, Dept Human Physiol, E-29071 Malaga, Spain

[2] Univ Malaga, Sch Med, Dept Pharmacol, E-29071 Malaga, Spain

[3] Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41100 Modena, Italy

[4] Karolinska Inst, Dept Neurosci, Stockholm, Sweden

[5] GlaxoSmithKline, Neurol GI, Ctr Excellence Drug Discovery, Harlow, Essex, England

来源：

NEUROREPORT | 2008年 / 19卷 / 06期

关键词：

basal ganglia; cyclooxygenase-2 inhibitor GW637185X; microdensitometry; mouse; neuroprotection; Parkinson's disease; stereology tyrosine hydroxylase; 1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine;

D O I：

10.1097/WNR.0b013e3282fb7898

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The possible neuroprotective role of a novel and highly selective cyclooxygenase-2 inhibitor GW637185X was studied in a model of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury of nigrostriatal dopaminergic (DA) neurons in the mouse. Stereological and microdensitometrical analysis of nigral tyrosine hydroxylase-immunoreactive cell bodies and striatal tyrosine hydroxylase-immunoreactive terminals, respectively, showed that GW637185X exerted a full protection against MPTP-induced degeneration of the nigro-striatal pathway. In contrast to earlier studies, these findings demonstrate that acute inhibition of cyclooxygenase-2 can result in a full neuroprotective effect not only on nigral DA cell bodies, but also on striatal DA terminals in the mouse MPTP model.

引用

页码：657 / 660

页数：4

共 26 条

[1]

AGNATI LF, 1984, ACTA PHYSIOL SCAND, P5

[2] Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP [J].

Aguirre, JA ;

Kehr, J ;

Yoshitake, T ;

Liu, FL ;

Rivera, A ;

Fernandez-Espinola, S ;

Andbjer, B ;

Leo, G ;

Medhurst, AD ;

Agnati, LF ;

Fuxe, K .

BRAIN RESEARCH, 2005, 1033 (02) :216-220

[3]

AGUIRRE JA, 2007, 7 IBRO WORLD C NEUR, P337

[4] Cyclooxygenase-2 inhibitor NS-398 protects neuronal cultures from lipopolysaccharide-induced neurotoxicity [J].

Araki, E ;

Forster, C ;

Dubinsky, JM ;

Ross, ME ;

Iadecola, C .

STROKE, 2001, 32 (10) :2370-2375

[5]

Brambilla R, 2001, ANN NY ACAD SCI, V939, P54

[6] Differential effects of acute and subchronic administration on phencyclidine-induced neuro degeneration in the perinatal rat [J].

Cheng, ZW ;

Johnson, KM .

JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 81 (02) :284-292

[7] COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice [J].

Feng, ZH ;

Li, DD ;

Fung, PCW ;

Pei, Z ;

Ramsden, DB ;

Ho, SL .

NEUROREPORT, 2003, 14 (15) :1927-1929

[8] Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra [J].

Feng, ZH ;

Wang, TG ;

Li, DD ;

Fung, P ;

Wilson, BC ;

Liu, B ;

Ali, SF ;

Langenbach, R ;

Hong, JS .

NEUROSCIENCE LETTERS, 2002, 329 (03) :354-358

[9]

GREEN RH, 2001, Patent No. 0138311

[10]

Hirsch EC, 2003, ANN NY ACAD SCI, V991, P214

← 1 2 3 →