Glia cell number modulates sensitivity to MPTP in mice

Smeyne, Michelle; Jiao, Yun; Shepherd, Kennie R.; Smeyne, Richard J.

doi:10.1002/glia.20233

Cited by 58 publications

(36 citation statements)

References 76 publications

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“…dopamine neurons) but a much more pervasive disorder that involves glial cells and neurons both within and beyond the nigra. This view is based on evidence from human studies [22][23][24][25][26][27] as well as from experimental PD models [28][29][30][31]. Therefore, it is obvious that, if one limits their experimental design to studying just one cell type, many important aspects of the disease will be missed.…”

Section: Transcriptome Analysis Reveals Link Between Proteasomal and mentioning

confidence: 99%

Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease

et al. 2006

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There is growing evidence that dysfunction of the mitochondrial respiratory chain and failure of the cellular protein degradation machinery, specifically the ubiquitin-proteasome system, play an important role in the pathogenesis of Parkinson's disease. We now show that the corresponding pathways of these two systems are linked at the transcriptomic level in Parkinsonian substantia nigra. We examined gene expression in medial and lateral substantia nigra (SN) as well as in frontal cortex using whole genome DNA oligonucleotide microarrays. In this study, we use a hypothesis-driven approach in analysing microarray data to describe the expression of mitochondrial and ubiquitin-proteasomal system (UPS) genes in Parkinson's disease (PD). Although a number of genes showed up-regulation, we found an overall decrease in expression affecting the majority of mitochondrial and UPS sequences. The down-regulated genes include genes that encode subunits of complex I and the Parkinson's-disease-linked UCHL1. The observed changes in expression were very similar for both medial and lateral SN and also affected the PD cerebral cortex. As revealed by "gene shaving" clustering analysis, there was a very significant correlation between the transcriptomic profiles of both systems including in control brains. Therefore, the mitochondria and the proteasome form a higher-order gene regulatory network that is severely perturbed in Parkinson's disease. Our quantitative results also suggest that Parkinson's disease is a disease of more than one cell class, i.e. that it goes beyond the catecholaminergic neuron and involves glia as well.

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Section: Transcriptome Analysis Reveals Link Between Proteasomal and mentioning

confidence: 99%

Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease

et al. 2006

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“…Antibodies directed against GFAP were used to detect astrocytosis and antibodies directed against Iba-1 was used to detect microgliosis (53). Activated caspase-3 and Fluoro-Jade-B staining to mark apoptotic and necrotic cells, respectively were examined as described in ref.…”

Section: Virus Stock Preparation and Inoculation Of Mice With H5n1mentioning

confidence: 99%

Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration

Jang

Boltz²,

Sturm‐Ramirez³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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404

362

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One of the greatest influenza pandemic threats at this time is posed by the highly pathogenic H5N1 avian influenza viruses. To date, 61% of the 433 known human cases of H5N1 infection have proved fatal. Animals infected by H5N1 viruses have demonstrated acute neurological signs ranging from mild encephalitis to motor disturbances to coma. However, no studies have examined the longer-term neurologic consequences of H5N1 infection among surviving hosts. Using the C57BL/6J mouse, a mouse strain that can be infected by the A/Vietnam/1203/04 H5N1 virus without adaptation, we show that this virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection. We also observe a significant loss of dopaminergic neurons in the substantia nigra pars compacta 60 days after infection. Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases. alpha-synuclein ͉ Parkinson's disease ͉ substantia nigra ͉ stereology ͉ encephalitis

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“…The damage to dopaminergic neurons in the nigrostriatal system caused by MPTP is very similar to that seen in idiopathic Parkinson disease (PD) (Mandel et al, 2007;Yokoyama et al, 2008). C57BL/6J mice (Eldad et al, 1990;Teismann et al, 2001;Xiao et al, 2004;Smeyne et al, 2005;He et al, 2008b) and several species of primates (Jenner, 2009;Johnston et al, 2010) sensitive to MPTP are currently used as animal models for idiopathic PD (Schapira et al, 2007). When injected into these animals, MPTP penetrates the blood-brain barrier (BBB) and is converted to 1-methyl-4-phenylpyridinium (MPP + ) by monoamine oxidase-B (MAO-B) in astrocytes (Levitt et al, 1982;Singer et al, 1986;Di Monte et al, 1992;O'Callaghan and Seidler, 1992;Ghosh et al, 2007;Chen et al, 2008;He et al, 2008a;Sonsalla et al, 2010).…”

Section: Introductionmentioning

confidence: 91%

Biochemical evaluation of the neurotoxicity of MPTP and MPP<sup>+</sup> in embryonic and newborn mice

2013

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-One of the toxicities caused by 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is damage to dopaminergic neurons. When injected into C57BL/6J mice, MPTP penetrates into the brain and is converted to 1-methyl-4-phenylpyridinium (MPP + ) by monoamine oxidase (MAO)-B in astrocytes. MPP + has high affinity for the dopamine transporter (DAT) on dopaminergic neurons, and is taken up into the cell to cause cell death. There have been relatively few researches on the acute MPTP toxicity to embryonic or newborn mice. In the present study, we attempted to evaluate the influence of MPTP and MPP + on embryonic and newborn mice by measuring sequential changes in major indexes of MPTP toxicity and MPTP metabolism; levels of Tyrosine Hydroxylase (TH), DAT, MAO-A and MAO-B. In addition, we measured the levels of dopamine and its metabolites, 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA), in the brain of newborn mice. A single injection of MPTP and MPP + reduced the levels of dopamine and its metabolites, DOPAC and HVA, in the brain of newborn mice about 6-12 hr after the injection. Similarly the levels of mRNAs and proteins of DAT and TH were lowered in the brain of embryonic and newborn mice as well. The levels of these indexes were generally recovered at 24 hr after injection, indicating that the neurotoxicity induced by a single injection of MPTP or MPP + is temporary and recoverable in embryonic and newborn mice. By contrast, no significant changes in the expression levels of MAO-A and MAO-B were observed in either MPTP-or MPP + -treated mice.

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Glia cell number modulates sensitivity to MPTP in mice

Cited by 58 publications

References 76 publications

Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease

Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease

Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration

Biochemical evaluation of the neurotoxicity of MPTP and MPP<sup>+</sup> in embryonic and newborn mice

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