Project description:We report RNA-sequencing from ventral mid brain and striatum from paraquat, pyridaben and paraquat+maneb mice models of Parkinson's disease. We observed several differentially expressed genes upon pesticide exposure which we analyzed by pathway analysis. We examined 3 replicates each for ventral mid brain and striatum per pesticide for RNA-Seq
Project description:We report RNA-sequencing from ventral mid brain and striatum from paraquat, pyridaben and paraquat+maneb mice models of Parkinson's disease. We observed several differentially expressed genes upon pesticide exposure which we analyzed by pathway analysis.
Project description:Bach1 is a known repressor of NRF2 transcription factor which governs oxidative stress during pathophysiology of Parkinson's disease. NRF2 activation in ventral midbrain is associated with protection against oxidative stress induced apoptosis of DA neurons. In this study we hve evaluated the effect of loss of Bach1 fucntion in ventral mid brains.
Project description:Strong evidence in human populations indicates that pesticide exposure increases the risk of Parkinson's disease . However, to date there has no study investigating the role of genetic pathways for pesticide induced PD at cellular resolution. We used single cell RNA sequencing to provide fine-grained information on the genetic pathways of Parkinson's disease caused by a combined regimen of maneb and paraquat. We investigated the substantia nigra pars compacta of control mice and mice treated with maneb and paraquat to identify changes in gene expression in cellular subpopulations such as neurons, glia and vascular cells. This work reveals how neuronal and non-neuronal cells interact in the context of a toxicologically and environmentally relevant model Parkinson's disease, while offering entry points to the design of new therapies.
Project description:Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor’s barrier avoidance, startled jumping, and retarded locomotion. Transcripts in hippocampus, amygdala, medial prefrontal cortex, ventral striatum (nucleus acumbens), septal region, corpus striatum, hemi-brain, blood, spleen and heart of stressed and control C57B/6 mice were analyzed using Agilent’s mouse genome-wide arrays.
Project description:Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. Functional and causal pathway analysis of gene expression and proteomic alterations in these three regions revealed pathways that correlated with deposition of alpha-synuclein. Microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release and other changes were reflected across all brain regions. Importantly a subset of these changes were replicated in Parkinson's disease blood. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany alpha-synculein pathology in Parkinson's disease, and may be instrumental in understanding and diagnosing Parkinson's disease progression. Substantia Nigra (3 normal, 3 PD), Striatum (6 normal, 6 PD), Cortex (5 normal, 5 PD), Cortex non-PD neurodegeneration (2 normal, 3 DLB). Note Sample X201264 was used both for Cortex normal and for Cortex nonPD normal
Project description:Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor’s barrier avoidance, startled jumping, and retarded locomotion. Transcripts in hippocampus, amygdala, medial prefrontal cortex, ventral striatum (nucleus acumbens), septal region, corpus striatum, hemi-brain, blood, spleen and heart of stressed and control C57B/6 mice were analyzed using Agilent’s mouse genome-wide arrays. C57B6 mice were exposed to SJL aggressor mice for periods of 5 days and 10days (6 hours each day) to induce anxiety/stress which parallels to PTSD in human Organs, blood and brain regions were collected after 24 hours and 1.5 week of post 5 days social defeat period; and 24 hour and 6 weeks post 10 days social stress period.
Project description:In this study we identify the gene expression changes that occur in the brain-localized immune cells in a mouse model of Parkinson's Disease. A mouse model of Parkinson's Disease was created as previously described by stereotacticaly injecting an AAV-expressing the human A53T_mutated form of a-Synuclein into the Substantia Nigra of adult mice, while control mice were injected with empty vector (EV). These mice exhibit neurodegeneration in the Substantia Nigra and Parkinson-like behaviour phenotypes. Sixteen weeks after the injection, the Substantia Nigra and Srtiatum were micro-dissected and a Percoll gradient was used to enrich for the immune cells present in these tissues. The immune cells were also isolated from the Substantia Nigra and Striatum of same-age WT uninjected mice (WT). RNA was isolated from these cells and single-end 75nt high throughput sequencing were performed on libraries prepared from the RNA. We identified over 400 genes that were differentially expressed between control and Parkinson's mice with a log2 fold-change > |0.75|. These genes were enriched for terms related to immune activation such as: cytokine processing, leukocyte activation, and antigen presentation. The genes associated with these GO terms tended to be up-regulated in the Parkinson's mice suggesting that brain-localized immune cells are more activated in Parkinson's disease.
Project description:Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. Functional and causal pathway analysis of gene expression and proteomic alterations in these three regions revealed pathways that correlated with deposition of alpha-synuclein. Microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release and other changes were reflected across all brain regions. Importantly a subset of these changes were replicated in Parkinson's disease blood. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany alpha-synculein pathology in Parkinson's disease, and may be instrumental in understanding and diagnosing Parkinson's disease progression.
