Neurotoxicity research
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Neurotoxicity research · May 2009
Neuroprotective effect of ghrelin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease by blocking microglial activation.
Ghrelin is an endogenous ligand for growth hormone (GH) secretagogue receptor 1a (GHS-R1a) and is produced and released mainly from the stomach. It was recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of Parkinson's disease (PD) neurodegeneration. However, the role of microglia in the neuroprotective properties of ghrelin is still unknown. ⋯ The inhibitory effect of ghrelin on the activation of microglia appears to be indirect by suppressing matrix metalloproteinase-3 (MMP-3) expression in stressed dopaminergic neurons because GHS-R1a is not expressed in SNpc microglial cells. Finally, in vitro administration of ghrelin prevented 1-methyl-4-phenylpyridinium-induced dopaminergic cell loss, MMP-3 expression, microglial activation, and the subsequent release of TNF-alpha, IL-1beta, and nitrite in mesencephalic cultures. Our data indicate that ghrelin may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that ghrelin may be a valuable therapeutic agent for neurodegenerative diseases such as PD.