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Lack of neuroprotection in the absence of P2X7 receptors in toxin-induced animal models of Parkinson's disease

Molecular Neurodegeneration, ISSN: 1750-1326, Vol: 6, Issue: 1, Page: 28
2011
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Background: Previous studies indicate a role of P2Xreceptors in processes that lead to neuronal death. The main objective of our study was to examine whether genetic deletion or pharmacological blockade of P2X receptors influenced dopaminergic cell death in various models of Parkinson's disease (PD). Results: mRNA encoding P2Xand P2X receptors was up-regulated after treatment of PC12 cells with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). P2Xantagonists protected against MPTP and rotenone induced toxicity in the LDH assay, but failed to protect after rotenone treatment in the MTT assay in PC12 cells and in primary midbrain culture. In vivo MPTP and in vitro rotenone pretreatments increased the mRNA expression of P2Xreceptors in the striatum and substantia nigra of wild-type mice. Basal mRNA expression of P2X receptors was higher in P2Xknockout mice and was further up-regulated by MPTP treatment. Genetic deletion or pharmacological inhibition of P2Xreceptors did not change survival rate or depletion of striatal endogenous dopamine (DA) content after in vivo MPTP or in vitro rotenone treatment. However, depletion of norepinephrine was significant after MPTP treatment only in P2Xknockout mice. The basal ATP content was higher in the substantia nigra of wild-type mice, but the ADP level was lower. Rotenone treatment elicited a similar reduction in ATP content in the substantia nigra of both genotypes, whereas reduction of ATP was more pronounced after rotenone treatment in striatal slices of P2Xdeficient mice. Although the endogenous amino acid content remained unchanged, the level of the endocannabinoid, 2-AG, was elevated by rotenone in the striatum of wild-type mice, an effect that was absent in mice deficient in P2Xreceptors. Conclusions: We conclude that P2Xreceptor deficiency or inhibition does not support the survival of dopaminergic neurons in an in vivo or in vitro models of PD. © 2011 Hracská et al; licensee BioMed Central Ltd.

Bibliographic Details

Hracskó, Zsuzsanna; Baranyi, Mária; Csölle, Cecilia; Gölöncsér, Flóra; Madarász, Emilia; Kittel, Agnes; Sperlágh, Beáta

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology; Medicine; Neuroscience

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