Expression Of MPGES-1 In Substantia Nigra Of Mice PD Models Induced By MPTP

Background More and more research showed that inflammatory activation was an important factor in the development of Parkinson disease(PD). Anti-inflammation is an effective method in prevention and therapy of PD. Cycloxygenase (COX-2), a rate-limiting enzyme in the metabolic pathway of arachidonic acid, and its product-prostaglandin E2 (PGE2) play important roles in the patients and some animal models of PD. The role of membrane-associated PGE2 synthase (mPGES-1), the last enzyme of producing PGE2, was unknown in the development of PD.Objective To detect the protein and mRNA expression of mPGES-1 in the substantia nigra (SN) of mice PD models caused by 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), and to further explore the possible mechanisms of prostaglandins inducing dopaminergic neuron degeneration in substantia nigra of PD, which would be helpful in finding specificity target in therapy and prevention of PD.Methods 24 well-being male C57BL/6N mice were randomly divided into two groups: MPTP-induced parkinsonism group (15mg/kg, ipX4/d) and control group (NS, ip×4/d). After intraperitoneal injection 24 hours, the midbrains were cut out for protein and mRNA detection individually. The tyrosine hydroxylase (TH) in substantia nigra were detected by immunohistochemistry method. The mPGES-1 protein in the substantia nigra was detected by immumofluorescence method. The relative quantitation of mRNA of mPGES-1 in the middle brain was measured by real-time fluorescence PCR technique.Results Compared with control mice, the number of TH positive neurons in the substantia nigra evidently reduced in MPTP-induced PD model mice ( P < 0. 01); There is no mPGES-1 positive cell in the substantia nigra area in control mice, while obvious mPGES-1 immumofluorescence positive cells were observed in the substantia nigra area in MPTP-induced PD model mice. The expression of mRNA of mPGES-1 was also increased in the midbrain in MPTP mice. Its relative content of mRNA was 1.49 times compared with control group. ConclusionMPTP results in dopaminergic neuron impairment in substantia nigra area in C57BL/6N mice, by which made the mice PD models.It is first time confirmed that the protein of mPGES-1 is over-expression in the substantia nigra in MPTP-induced PD model mice, suggesting that mPGES-1 has relationship with the degeneration of dopaminergic neurons in substantia nigra in MPTP models.The mRNA of mPGES-1 is over-expression in the midbrain in MPTP-induced PD model mice, suggesting that the increase of mPGES-1 is in transcription level as well.