Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,545 bioRxiv papers from 297,698 authors.
Genetic liability for internalizing versus externalizing behavior manifests in the developing and adult hippocampus: Insight from a meta-analysis of transcriptional profiling studies in a selectively-bred rat model
Isabelle A. Birt,
Megan Hastings Hagenauer,
Sarah M. Clinton,
John D.H. Stead,
Kathryn L. Hilde,
Robert C Thompson,
Elaine K. Hebda-Bauer,
Stanley J. Watson,
Posted 23 Sep 2019
bioRxiv DOI: 10.1101/774034
Posted 23 Sep 2019
Background For over 16 years, we have selectively bred rats to show either high or low levels of exploratory activity within a novel environment. These “bred High Responder” (bHR) and “bred Low Responder” (bLR) rats serve as a model for temperamental extremes, exhibiting large differences in many internalizing and externalizing behaviors relevant to mood and substance abuse disorders. Methods Our study elucidated persistent differences in gene expression related to bHR/bLR phenotype across development and adulthood in the hippocampus, a region critical for emotional regulation. We meta-analyzed eight transcriptional profiling datasets (microarray, RNA-Seq) spanning 43 generations of selective breeding (adult: n =46, P7: n =22, P14: n =49, P21: n =21; all male). We cross-referenced these results with exome sequencing performed on our colony to pinpoint candidates likely to mediate the effect of selective breeding on behavioral phenotype. Results Genetic and transcriptional profiling results converged to implicate two genes with previous associations with metabolism and mood: Thyrotropin releasing hormone receptor and Uncoupling protein 2. Our results also highlighted bHR/bLR functional differences in the hippocampus, including a network essential for neurodevelopmental programming, proliferation, and differentiation, containing hub genes Bone morphogenetic protein 4 and Marker of proliferation ki-67. Finally, we observed differential expression related to microglial activation, which is important for synaptic pruning, including two genes within implicated chromosomal regions: Complement C1q A chain and Milk fat globule-EGF factor 8. Conclusion These candidate genes and functional pathways have the capability to direct bHR/bLR rats along divergent developmental trajectories and promote a widely different reactivity to the environment.
- Downloaded 97 times
- Download rankings, all-time:
- Site-wide: 62,583 out of 67,466
- In neuroscience: 11,165 out of 12,095
- Year to date:
- Site-wide: 50,404 out of 67,466
- Since beginning of last month:
- Site-wide: 13,998 out of 67,466
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!