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pmid:25100957
Environmental enrichment alters protein expression as well as the proteomic response to cocaine in rat nucleus accumbens.
Cheryl F Lichti · Xiuzhen Fan · Robert D English · Yafang Zhang · Dingge Li · Fanping Kong · Mala Sinha · Clark R Andersen · Heidi Spratt · Bruce A Luxon · Thomas A Green
Frontiers in behavioral neuroscience · 2014 doi:10.3389/fnbeh.2014.00246
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Complete file
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Understanding the mechanisms underlying this phenotype will guide selection of targets for much-needed novel pharmacotherapeutics. The current study investigates differences in proteome expression in the nucleus accumbens of enriched and isolated rats and the proteomic response to cocaine self-administration using a liquid chromatography mass spectrometry (LCMS) technique to quantify 1917 proteins. Results of complementary Ingenuity Pathways Analyses (IPA) and gene set enrichment analyses (GSEA), both performed using protein quantitative data, demonstrate that cocaine increases vesicular transporters for dopamine and glutamate as well as increasing proteins in the RhoA pathway. Further, cocaine regulates proteins related to ERK, CREB and AKT signaling. Environmental enrichment altered expression of a large number of proteins implicated in a diverse number of neuronal functions (e.g., energy production, mRNA splicing, and ubiquitination), molecular cascades (e.g., protein kinases), psychiatric disorders (e.g., mood disorders), and neurodegenerative diseases (e.g., Huntington's and Alzheimer's diseases). Upregulation of energy metabolism components in EC rats was verified using RNA sequencing. Most of the biological functions and pathways listed above were also identified in the Cocaine X Enrichment interaction analysis, providing clear evidence that enriched and isolated rats respond quite differently to cocaine exposure. The overall impression of the current results is that enriched saline-administering rats have a unique proteomic complement compared to enriched cocaine-administering rats as well as saline and cocaine-taking isolated rats. These results identify possible mechanisms of the protective phenotype and provide fertile soil for developing novel pharmacotherapeutics. Proteomics data are available via ProteomeXchange with identifier PXD000990.", "claims": [{"id": "claim-method", "statement": "The resulting proteins were quantified by Two-Way ANOVA, and p-value adjustment was performed according to the Benjamini and Hochberg method (Benjamini and Hochberg, 1995).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25100957", "locator": "sections[8] \"Proteomic data analysis\" paragraph 2", "quote": "The resulting proteins were quantified by Two-Way ANOVA, and p-value adjustment was performed according to the Benjamini and Hochberg method (Benjamini and Hochberg, 1995)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository (Vizcaino et al., 2014) with the dataset identifier PXD000990.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25100957", "locator": "sections[35] \"Acknowledgments\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository (Vizcaino et al., 2014) with the dataset identifier PXD000990."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The headline result was that cocaine increased vesicular dopamine and glutamate transporters and proteins in the RhoA pathway, while environmental enrichment broadly altered the nucleus accumbens proteome; statistical inference used complementary IPA and protein-based GSEA, and the proteomics source data are available through ProteomeXchange identifier PXD000990.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25100957"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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