Dataset Information

Expression miRNA data from human postmortem putamen samples measured using the NanoString nCounter platform

ABSTRACT: Background: Molecular adaptations in the striatum mediated by dopamine (DA) denervation or Levodopa (L-dopa) treatment have been implicated with the motor deficits found in Parkinson’s disease (PD). Alterations in glutamatergic neurotransmission and anti-oxidant mechanisms are reported to play important roles in mediating these changes. However, the mechanisms mediating the molecular adaptations in the striatum are not well understood. In recent years, microRNAs (miRNAs) have been recognized as potent post-transcriptional regulators of gene expression with fundamental roles in numerous biological processes. miRNAs are known to influence the development and maintenance of striatal neurons. Therefore, we sought to determine the genome-wide expression levels of miRNAs in PD striatal tissues. Methods: Using a digital gene expression platform to quantify miRNA levels, we compared the expression of 800 miRNAs in human postmortem putamen tissues from PD patients and controls. Results: We detected the expression of approximately 250 miRNAs in postmortem human putamen samples collected from patients with PD and healthy controls. There was an abundance of a subset of 17 miRNAs (10 up- and 7 down-regulated) differing substantially between PD and the control tissues. Conclusions: We identified deregulated miRNAs most likely associated with altered striatal functions found in PD. This approach may provide insight into pathogenesis and additional therapeutic targets for the development novel treatment strategies for the disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77667 | GEO | 2016/06/30

SECONDARY ACCESSION(S): PRJNA311174

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Molecular adaptations in the striatum mediated by dopamine (DA) denervation or Levodopa (L-dopa) treatment have been implicated with the motor deficits found in Parkinsonâ??s disease (PD). Alterations in glutamatergic neurotransmission and anti-oxidant mechanisms are reported to play important roles in mediating these changes. However, the mechanisms mediating the molecular adaptations in the striatum are not well understood. In recent years, microRNAs (miRNAs) have been recognized as potent post-transcriptional regulators of gene expression with fundamental roles in numerous biological processes. miRNAs are known to influence the development and maintenance of striatal neurons. Therefore, we sought to determine the genome-wide expression levels of miRNAs in PD striatal tissues. Methods: Using a digital gene expression platform to quantify miRNA levels, we compared the expression of 800 miRNAs in human postmortem putamen tissues from PD patients and controls. Results: We detected the expression of approximately 250 miRNAs in postmortem human putamen samples collected from patients with PD and healthy controls. There was an abundance of a subset of 17 miRNAs (10 up- and 7 down-regulated) differing substantially between PD and the control tissues. Conclusions: We identified deregulated miRNAs most likely associated with altered striatal functions found in PD. This approach may provide insight into pathogenesis and additional therapeutic targets for the development novel treatment strategies for the disease. Human postmortem putamen tissues from 12 patients with PD symptoms and 12 neurologically normal controls. Samples were obtained from the Human Brain and Spinal Fluid Resource Center, Los Angeles, CA through NIH NeuroBioBank, and stored at -80Â°C until RNA isolation. Total RNA was extracted using the miRVana RNA isolation kit, following the manufacturerâ??s instructions (Ambion). Using 225ng total RNA, miRNA levels were assayed by direct digital detection using Nanostring miRNA assay kits (Nanostring Technologies).

Project description:Background: Molecular adaptations in the striatum mediated by dopamine (DA) denervation or Levodopa (L-dopa) treatment have been implicated with the motor deficits found in Parkinsonâs disease (PD). Alterations in glutamatergic neurotransmission and anti-oxidant mechanisms are reported to play important roles in mediating these changes. However, the mechanisms mediating the molecular adaptations in the striatum are not well understood. In recent years, microRNAs (miRNAs) have been recognized as potent post-transcriptional regulators of gene expression with fundamental roles in numerous biological processes. miRNAs are known to influence the development and maintenance of striatal neurons. To determine the contribution of miRNAs in molecular adaptations found in PD, we screened the expression of 800 miRNAs in postmortem striatum samples obtained from PD and neurologically normal controls. We detected the expression of approximately 250 miRNAs in postmortem human putamen samples collected from patients with PD and healthy controls. There was an abundance of a subset of 17 miRNAs (10 up- and 7 down-regulated) differing substantially between PD and the control, suggesting that miRNAs are altered in the striatum during the course of PD. Computational analysis show that many of these miRNAs targets pro-inflammatory factors in the striatum. Therefore, we sought to detrmine the expression of experimentally validated pro-inflammatory transcripts in PD striatum. Methods: Using a digital gene expression platform to quantify 134 gene transcripts, we compared human postmortem putamen tissues from patients with PD and neurologically normal controls. Results: We identified deregulated expression of 10 gene transcripts (4 up- and 6 down-regulated mRNAs) in postmortem human putamen samples collected fromPD patients compared to controls. The expression of these genes negative correlates with the expression of many of the differentially epxressed miRNAs. Moreover, many of these genes are predicted targets of the differentially expressed miRNAs. Conclusions: We identified deregulated mRNAs most likely associated with anti-oxidant mechanims in PD striatum. This approach may provide insights into pathogenesis of the disease. Human postmortem putamen tissues from 12 patients with PD symptoms and 12 neurologically normal controls were used in the study. Samples were obtained from the Human Brain and Spinal Fluid Resource Center, Los Angeles, CA through NIH NeuroBioBank, and stored at -80Â°C until RNA isolation. Total RNA was extracted using the mirVana RNA isolation kit, following the manufacturerâs instructions (Ambion). Using 225ng total RNA, mRNA levels were assayed by direct digital detection using Nanostring nCounter assay kits (Nanostring Technologies).

Project description:Background: Molecular adaptations in the striatum mediated by dopamine (DA) denervation or Levodopa (L-dopa) treatment have been implicated with the motor deficits found in Parkinson’s disease (PD). Alterations in glutamatergic neurotransmission and anti-oxidant mechanisms are reported to play important roles in mediating these changes. However, the mechanisms mediating the molecular adaptations in the striatum are not well understood. In recent years, microRNAs (miRNAs) have been recognized as potent post-transcriptional regulators of gene expression with fundamental roles in numerous biological processes. miRNAs are known to influence the development and maintenance of striatal neurons. To determine the contribution of miRNAs in molecular adaptations found in PD, we screened the expression of 800 miRNAs in postmortem striatum samples obtained from PD and neurologically normal controls. We detected the expression of approximately 250 miRNAs in postmortem human putamen samples collected from patients with PD and healthy controls. There was an abundance of a subset of 17 miRNAs (10 up- and 7 down-regulated) differing substantially between PD and the control, suggesting that miRNAs are altered in the striatum during the course of PD. Computational analysis show that many of these miRNAs targets pro-inflammatory factors in the striatum. Therefore, we sought to detrmine the expression of experimentally validated pro-inflammatory transcripts in PD striatum. Methods: Using a digital gene expression platform to quantify 134 gene transcripts, we compared human postmortem putamen tissues from patients with PD and neurologically normal controls. Results: We identified deregulated expression of 10 gene transcripts (4 up- and 6 down-regulated mRNAs) in postmortem human putamen samples collected fromPD patients compared to controls. The expression of these genes negative correlates with the expression of many of the differentially epxressed miRNAs. Moreover, many of these genes are predicted targets of the differentially expressed miRNAs. Conclusions: We identified deregulated mRNAs most likely associated with anti-oxidant mechanims in PD striatum. This approach may provide insights into pathogenesis of the disease.

Project description:L-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease. To profile the cell-type-specific responses of striatal spiny projection neurons (SPNs) to striatal dopamine depletion, we conducted TRAP analysis of the two major classes of these neurons: dSPNs that express the dopamine receptor 1a (Drd1a), and iSPNs that express the dopamine receptor 2 (Drd2). To disrupt dopamine innervation to both of these SPN populations that reside in the striatum, we injected the neurotoxin 6-hydroxydopamine (6-OHDA), unilaterally, in the medial forebrain bundle (MFB) in hemizygous Drd1-TRAP and Drd2-TRAP adult (9-14 weeks) male mice (kept on a C57BL/6J genetic background). This lesion procedure causes nigral dopamine cell death within a few days, along with a widespread and near-complete loss of dopaminergic innervation to the entire dorsal striatum on one side of the brain (a hemiparkinsonian model). We first examined the effects of dopamine depletion alone, compared to a mock lesion (ascorbate / saline injected). We then examined the effects of chronic levodopa treatment upon the molecular profiles of dopamine- depleted dSPNs and iSPNs, with two dose regimens. The ‘high-dose’ L-DOPA regimen (3 mg/kg on days 1-3, followed by 6 mg/kg on days 4-9) was expected to induce severe dyskinesia in all MFB-lesioned mice. The low-dose L-DOPA regimen (1 mg/kg on days 1-3, followed by 2 mg/kg on days 4-9) was expected to reverse limb use asymmetry without causing conspicuous dyskinesias. To equalize the effects of stress and handling across all groups, including control groups, all mice were equally handled and thus received saline injections when not receiving levodopa injections. Each treatment group contained 7-10 replicates. TRAP-purified mRNAs from either Drd1a- or Drd2-expressing SPNs were reverse-transcribed, amplified, and used to interrogate Affymetrix 430_2.0 GeneChip microarrays.

Dataset Information

Expression miRNA data from human postmortem putamen samples measured using the NanoString nCounter platform

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets