Project description:In Parkinsonâ??s disease (PD), the progressive loss of substantia nigra dopamine cells has been associated with their vulnerability to oxidative stress, inflammation, and mitochondrial dysfunction. To identify multiple gene transcription alterations that may potentially underlie early stages of related degenerative processes in brain, we used the subcrhonic MPTP mouse model of PD and microarray analysis at 4 days post-MPTP when neurotoxic activity is maximal. Since PD results in gene changes throughout the brain, we assessed MPTP's effects in multiple regions: frontal cortex, striatum and midbrain. Experiment Overall Design: Mus musculus adults were randomly assigned to either MPTP or saline treatment groups. Brain regions of interest (frontal cortex, striatum and midbrain) were dissected from both groups for RNA extraction and hybridization on Affymetrix microarrays.
Project description:In Parkinson’s disease (PD), the progressive loss of substantia nigra dopamine cells has been associated with their vulnerability to oxidative stress, inflammation, and mitochondrial dysfunction. To identify multiple gene transcription alterations that may potentially underlie early stages of related degenerative processes in brain, we used the subcrhonic MPTP mouse model of PD and microarray analysis at 4 days post-MPTP when neurotoxic activity is maximal. Since PD results in gene changes throughout the brain, we assessed MPTP's effects in multiple regions: frontal cortex, striatum and midbrain. Keywords: neurotoxic response
Project description:PD is the second most common neurodegenerative disease worldwide with growing prevalence. MPTP is a neurotoxin which causes the appearance of Parkinson's disease (PD) pathology. The involvement of the cholinergic system in PD has been identified decades ago and anti-cholinergic drugs were upon the first drugs used for symptomatic treatment of PD. Of note, MPTP intoxication is a model of choice for symptomatic neuroprotective therapies since it have been quite predictive. Mice were exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), with or without the protective acetylcholinesterase (AChE-R) variant. Transgenic AChE-S (the synaptic variant), AChE-R (the shorter, protective variant) and FVB/N control mice were included in this study. Two brain regions were examined: the pre-frontal cortex (PFC) and the striatal caudate-putamen (CPu). Each condition (i.e brain region and transgenic variant) was examined on both naive and MPTP-exposed mice. 29 microarrays including hybridizations of control FVB/N PFC, control FVB/N CPu,control S transgenics PFC, control S transgenics CPu, control R transgenics PFC, control R transgenice CPu, MPTP FVB/N PFC, MPTP FVB/N CPu, MPTP S transgenics PFC, MPTP S transgenics CPu, MPTP R transgenics PFC and MPTP R transgenice CPu mRNA.
Project description:PD is the second most common neurodegenerative disease worldwide with growing prevalence. MPTP is a neurotoxin which causes the appearance of Parkinson's disease (PD) pathology. The involvement of the cholinergic system in PD has been identified decades ago and anti-cholinergic drugs were upon the first drugs used for symptomatic treatment of PD. Of note, MPTP intoxication is a model of choice for symptomatic neuroprotective therapies since it have been quite predictive. Mice were exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), with or without the protective acetylcholinesterase (AChE-R) variant. Transgenic AChE-S (the synaptic variant), AChE-R (the shorter, protective variant) and FVB/N control mice were included in this study. Two brain regions were examined: the pre-frontal cortex (PFC) and the striatal caudate-putamen (CPu). Each condition (i.e brain region and transgenic variant) was examined on both naive and MPTP-exposed mice.
Project description:Parkinson's disease pathogenesis proceeds through several phases, culminating in the loss of dopaminergic neurons of the substantia nigra (SN). Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of oxidative SN injury is frequently used to study degeneration of dopaminergic neurons in mice and non-human primates, an understanding of the temporal sequence of molecular events from inhibition of mitochondrial complex 1 to neuronal cell death is limited. Here, microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration. This approach enabled the identification of small, yet consistently significant, changes in gene expression within the SN of MPTP-treated animals. Such an analysis disclosed dysregulation of genes in three main areas related to neuronal function: cytoskeletal stability and maintenance, synaptic integrity, and cell cycle and apoptosis. The discovery and validation of these alterations provide molecular evidence for an evolving cascade of injury, dysfunction, and cell death. Keywords: Parkinson's disease; MPTP; gene expression; microarray; cytoskeleton; mouse
2006-05-12 | GSE4788 | GEO
Project description:Transcriptional analysis of multiple brain regions in Parkinson's disease
Project description:Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms. This SuperSeries is composed of the following subset Series: GSE20168: Transcriptional analysis of prefrontal area 9 in Parkinson's disease GSE20291: Transcriptional analysis of putamen in Parkinson's disease GSE20292: Transcriptional analysis of whole substantia nigra in Parkinson's disease Refer to individual Series