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:The goal of this study was A) to compare the global RNA-sequencing (RNA-seq) profiles data of the neurovascular units constructed in i) conventional cell cultures (n=4), ii) Substantia Nigra Brain-Chips cultured under constant flow (n=4), and iii) human adult brain-derived substantia nigra (n=8) retrieved from the Genotype-Tissue Expression (GTEx) Portal, B) to identify differences in the transcriptome profiles in brain endothelial cells between the two conditions, αSyn fibrils and αSyn monomers.
Project description:Analysis of substantia nigra from postmortem brains of 4 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra.
Project description:We report differnces to gene expression in the Dorsal Striatum, Ventral Striatum, Ventral Tegmental Area and Substantia Nigra in adult offspring as a consequence of Maternal HFD exposure during lactation.
Project description:RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain
Project description:There is a strong correlation between aging and onset of idiopathic Parkinson’s disease, but little is known about whether cellular changes occur during normal aging that may explain this association. Here, proteomic and bioinformatic analysis was conducted on the substantia nigra of rats at four stages of life to identify and quantify protein changes throughout aging. This analysis revealed that proteins associated with cell adhesion, protein aggregation and oxidative-reduction are dysregulated as early as middle age in rats. Glial fibrillary acidic protein (GFAP) was identified as a network hub connecting the greatest number of proteins altered during aging. Furthermore, the isoform of GFAP expressed in the substantia nigra varied throughout life. However, the expression levels of the rate-limiting enzyme for dopamine production, tyrosine hydroxylase (TH), was maintained even in the oldest animals, despite a reduction in the number of dopamine neurons in the SNc as aging progressed. This age-related increase in TH expression per neuron would likely to increase the vulnerability of neurons, since increased dopamine production would be an additional source of oxidative stress. This, in turn, would place a high demand on support systems from local astrocytes, which themselves show protein changes that could affect their functionality. Taken together, this study highlights key processes that are altered with age in the rat substantia nigra, each of which converge upon GFAP. These findings offer insight into the relationship between aging and increased challenges to neuronal viability, and indicate an important role for glial cells in the aging process.
