Project description:MPTP treated Macaca fascicularis prefrontal cortices compared to saline treated and untreated controls Experiment Overall Design: Macaques injected daily with Experiment Overall Design: MPTP hydrochloride (0.2 mg/kg, or with saline. Each group consisted of
Project description:To characterize both short- and long-term (7 days and 28 days) gene expression profiling differences between control and MPTP-treated retina, we determined levels of gene expression using microarray analysis and real-time PCR. We found 60 genes relatively regulated in retinas treated with MPTP for 7 days (26 up-regulated and 34 down-regulated), whereas 54 genes were regulated in retinas treated with MPTP for 28 days (18 up-regulated and 36 down-regulated) when compared with the non-treated retina in each control groups. Total 26 annotated differently expressed genes were chosen for further validation by quantitative real-time PCR, and 4 genes in the 7-day treatment group (Clec2e; Dio2; Hmcn1; Rlbp1) and 3 genes in the 28-days treatment group (Pnmt; Tmem121; Ssxb3) were confirmed.
Project description:To characterize both short- and long-term (7 days and 28 days) gene expression profiling differences between control and MPTP-treated retina, we determined levels of gene expression using microarray analysis and real-time PCR. We found 60 genes relatively regulated in retinas treated with MPTP for 7 days (26 up-regulated and 34 down-regulated), whereas 54 genes were regulated in retinas treated with MPTP for 28 days (18 up-regulated and 36 down-regulated) when compared with the non-treated retina in each control groups. Total 26 annotated differently expressed genes were chosen for further validation by quantitative real-time PCR, and 4 genes in the 7-day treatment group (Clec2e; Dio2; Hmcn1; Rlbp1) and 3 genes in the 28-days treatment group (Pnmt; Tmem121; Ssxb3) were confirmed. Male C57BL/6 mice were randomly divided into four treatment groups (n= 6 in each group): the 7 days and 28 days saline-injection (control) groups (C-7 and C-28, respectively), and 7 days and 28 days MPTP-injection groups (M-7 and M-28, respectively). 4 retinas for 1 samples (1 gene chip), (4 experimental group × 2 samples of each experimental group = total 8 samples).
Project description:Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effects on Parkinson's disease. To examine the role of irisin in PD, irisin was peripherally delivered before or after the establishment of PD models by MPTP to explore its effect. We performed mRNA analysis in the midbrain of MPTP treated mice with irisin pre-treatment or delayed-treatment through RNA-Sequencing. And bioinformatic analysis was done on the identified deregulated genes through gene ontology (GO) analysis, KEGG pathway analysis and Gene set enrichment analysis (GSEA). Pathway analysis indicated that NAD(P)H activity and metabolism, PI3K-AKT pathway, MAPK pathway, inflammation-related signaling pathways played vital roles in the treatment of MPTP treated mice by irisin pre-treatment and irisin delayed treatment. This study provides a detailed analysis of the effects and underlying mechanisms of irisin treatment in MPTP treated mice.
Project description:To characterize more broadly the effect of attenuated TLR4 signaling responses in sooty mangabeys, we performed a comparative RNA-seq profiling of LPS-treated primary monocytes from rhesus macaques and sooty mangabeys. Production of TNF- and IL6 mRNA was significantly lower in sooty mangabeys. Moreover, we observed that induction of NF-κB -regulated inflammatory genes was broadly and significantly reduced in sooty mangabeys, for TNF-a and IL-6 signaling pathways, compared to rhesus macaques. Overall, these data indicate that LPS stimulation of SM blood cells results in a significantly blunted production of pro-inflammatory cytokines as compared to rhesus macaque macrophages.
Project description:Implications for neuroprotection in Parkinson's disease Parkinson’s disease and its characteristic symptoms are thought to arise from the progressive degeneration of specific midbrain dopamine (DA) neurons. In humans, DA neurons of the substantia nigra (SN) and their projections to the striatum show selective vulnerability, while neighboring DA neurons of the ventral tegmental area (VTA) are relatively spared from degeneration. This pattern of cell loss is mimicked in humans, primates, and certain rodents by the neurotoxin MPTP. In this study, we aimed to test the hypothesis that there are factors in the VTA that are potentially neuroprotective against MPTP and that these factors change over time. We have found a differential transcriptional response within the cells of the SN and VTA to sustained exposure to a low dose of MPTP. Specifically, the VTA has increased expression of 148 genes as an early response to MPTP and 113 genes as a late response to MPTP toxicity. This response encompasses many areas of cellular function, including protein regulation (Phf6) and ion/metal regulation (PANK2, Car4). Notably, these responses were largely absent from the cells of the SN. Our data show a clear dynamic response in maintaining the homeostasis and viability of the neurons in the VTA that is lacking in the SN after neurotoxin challenge. We used microarrays to analyze the differential response of the substantia nigra (SN) and ventral tegmental area (VTA) to a chronic low dose of the neurotoxin MPTP. Transgenic hTH-GFP mice were treated with MPTP (4mg/kg) for either 2 or 10 days. Control mice were given an equal volume of saline for 10 days. Dopamine neurons from the substantia nigra and ventral tegmental areas of control and MPTP treated animals were laser captured. The RNA was isolated and processed for microarray hybridization. Each group had three biological replicates, for a total of 18 samples. Three each in the following: Control SN, Control VTA, 2 day MPTP SN, 2 day MPTP VTA, 10 day MPTP SN, 10 day MPTP VTA. Samples were log2 transformed and RMA normalized using Agilent Genespring 10.0 GX.
Project description:We characterized the transcriptomic profiles of cells from the substantia nigra (SN) of mice with co-injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and selective inhibitor of GCase activity (conduritol-β-epoxide, (CBE)) to mimic PD bearing GCase dysfunction (MPTP+CBE), mice treated with MPTP, mice treated with CBE and control mice treated with injec-tion of sodium chloride (NaCl) (vehicle).