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| Status |
Public on Jun 02, 2020 |
| Title |
Hippocampal Gene Expression in bred High Responder (bHR) vs. bred Low Responder (bLR) Rats: Affymetrix Microarray Data from Generation F4 |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This Affymetrix (Rat Expression Set 230 A) microarray study examined gene expression in the hippocampus in generation F4 adult male bHR rats and bLR rats (n=6 per group).
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| Overall design |
Overall Design: This microarray study examined gene expression in the hippocampus in generation F4 adult male bHR rats and bLR rats (n=6 per group). Behavioral testing: Locomotor response to a novel environment was assessed between age P50–75 as part of our selective breeding paradigm (protocol: Stead et al., 2006, Behav Genet. 36: 697–712). Sacrifice & RNA Extraction: The rats were sacrificed in adulthood (between P102-P108) via rapid decapitation followed by immediate brain extraction. The whole hippocampus, frontal cortex, and hypothalamus samples were rapidly dissected on ice, fast-frozen at –40°C, and stored at –80°C before processing. TRIzol reagent (Invitrogen, Calsbad, CA) was used to extract total RNA, followed by purification using RNeasy RNA purification columns (Qiagen, Valencia, CA). The quality and concentration of the RNA was determined using an Agilent bioanalyzer (Palo Alto, CA) and wavelength absorbance (260/280 nm ratio) by Nanodrop. Microarray: The samples were transcriptionally profiled using Affymetrix Rat Expression Set 230 A (RAE230A) microarray according to standard manufacturer’s procedures. The samples were run in two batches: the first included the hippocampus and cortex samples and the second included the hypothalamus samples. Each brain region was run on a separate chip. Only data from the hippocampal samples are included in this data release. Microarray Data Preprocessing: For our current analyses, the ReadAffy() function (from R package affy version 1.54.0; Gautier et al. 2004, Bioinformatics. 20: 307–315) was used to read the data from the hippocampal Affymetrix .CEL files into R studio (R Studio v.1.0.153, R v.3.2.2). An expression set was generated using the Robust Multi-Array Average method (RMA: Irizarry et al. 2003, Biostatistics. 4: 249–264). Using a custom .cdf (Dai et al. 2005, Nucleic Acids Res. 33: e175) we summarized the probe signals into probesets for the RAE230A chip (“rae230arnentrezgcdf_19.0.0”) which mapped the probe sequences to Entrez Gene IDs (downloaded from http://nmg-r.bioinformatics.nl/NuGO_R.html on Jan 2017, release date Nov 2015). We re-annotated the data according to Official Gene Symbol using the function org.Rn.egSYMBOL() from the R package org.Rn.eg.db (version 3.4.1; Carlson 2017, http://bioconductor.org/packages/org.Rn.eg.db/), and then removed rows lacking annotation (leaving 9,959 gene symbols). Quality control identified two samples with low sample-sample correlation values (around 0.66: 13F4-H07M1.1-HPC-HR-1 and 22F4-L08M2.0-HPC-LR-5), leaving a final sample size of n=5 per group. The full analysis code is available at: https://github.com/isabellie4/PhenotypeProject and https://github.com/hagenaue/bHRbLR_MetaAnalysisProject.
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| Contributor(s) |
Hagenauer MH, Stead JD, Birt IA, Watson SJ Jr, Akil H |
| Citation(s) |
32762937 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P01 DA021633 |
Antecedents & Consequences of Drug Abuse: Heritability, Stress & Neurplasticity |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
HUDA AKIL |
| P01 MH042251 |
DEVELOPMENTAL STUDIES--DIFFERENCES IN EMOTIONAL REACT |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
HUDA AKIL |
| R01 DA013386 |
Stress & Vulnerability to Drug Abuse: Neural Correlates |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
HUDA AKIL |
| P01 DA021633 |
COCAINE IMPACT ON NEURAL PLASTICITY MODULATION BY GENETIC VULNERABILITY & STRESS |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
STANLEY J WATSON |
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| Submission date |
Nov 18, 2019 |
| Last update date |
Sep 01, 2020 |
| Contact name |
Megan Hastings Hagenauer |
| E-mail(s) |
hagenaue@umich.edu
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| Organization name |
University of Michigan
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| Department |
MBNI
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| Lab |
Dr. Huda Akil & Dr. Stanley Watson
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| Street address |
205 Zina Pitcher Pl.
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL27768 |
[RAE230A] Affymetrix Rat Expression Set 230 [CDF: Brainarray Entrez Gene version 19.0] |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE140599 |
Hippocampal Gene Expression in bred High Responder (bHR) vs. bred Low Responder (bLR) Rats |
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| Relations |
| BioProject |
PRJNA590228 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140596_RAW.tar |
30.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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