SynthesisBiological psychiatry2021
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.
Synthesis in Biological psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Effects of 6-months of SSRI use on DNA-methylation and gene expression in blood.Brain, behavior, and immunity · 2026Trial
- Differential acquisition of cocaine and heroin self-administration in a rat model of internalizing versus externalizing temperament.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic markers of disease risk and psychotherapy response in anxiety disorders - a longitudinal analysis of the DNA methylome.Molecular psychiatry · 2025Article
- Nandrolone alters the behavioral response to cocaine as well as striatal and cortical dopamine receptors of prepubertal male rats.Scientific reports · 2025Article
- Bioenergetic-related gene expression in the hippocampus predicts internalizing vs. externalizing behavior in an animal model of temperament.Frontiers in molecular neuroscience · 2025Article
- Article
- Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype.Neurobiology of stress · 2024Article
- Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype.bioRxiv : the preprint server for biology · 2024Article
- Resource: A Curated Database of Brain-Related Functional Gene Sets (Brain.GMT).bioRxiv : the preprint server for biology · 2024Article
- Corticosteroid Treatment During Sepsis Alters Hippocampal Function in Male and Female Survivors.Biological psychiatry global open science · 2024Article
- Genetic and epigenetic studies of opioid abuse disorder - the potential for future diagnostics.Expert review of molecular diagnostics · 2023Review
- Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat.Nutrients · 2022Article
- Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model.Translational psychiatry · 2022Article
- Genome-wide association study in a rat model of temperament identifies multiple loci for exploratory locomotion and anxiety-like traits.Frontiers in genetics · 2022Article
- Sex-Specific Brain Transcriptional Signatures in Human MDD and Their Correlates in Mouse Models of Depression.Frontiers in behavioral neuroscience · 2022Review
- Examining the Role of Microbiota in Emotional Behavior: Antibiotic Treatment Exacerbates Anxiety in High Anxiety-Prone Male Rats.Neuroscience · 2021Article
- Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety.Frontiers in molecular neuroscience · 2021Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundFor more than 16 years, we have selectively bred rats for either high or low levels of exploratory activity within a novel environment. These bred high-responder (bHR) and bred low-responder (bLR) rats model temperamental extremes, exhibiting large differences in internalizing and externalizing behaviors relevant to mood and substance use disorders.
methodsWe characterized persistent differences in gene expression related to bHR/bLR phenotype across development and adulthood in the hippocampus, a region critical for emotional regulation, by meta-analyzing 8 transcriptional profiling datasets (microarray and RNA sequencing) spanning 43 generations of selective breeding (postnatal day 7: n = 22; postnatal day 14: n = 49; postnatal day 21: n = 21; adult: n = 46; all male). We cross-referenced expression differences with exome sequencing within our colony to pinpoint candidates likely to mediate the effect of selective breeding on behavioral phenotype. The results were compared with hippocampal profiling from other bred rat models.
resultsGenetic and transcriptional profiling results converged to implicate multiple candidate genes, including two previously associated with metabolism and mood: Trhr and Ucp2. Results also highlighted bHR/bLR functional differences in the hippocampus, including a network essential for neurodevelopmental programming, proliferation, and differentiation, centering on Bmp4 and Mki67. Finally, we observed differential expression related to microglial activation, which is important for synaptic pruning, including 2 genes within implicated chromosomal regions: C1qa and Mfge8.
conclusionsThese candidate genes and functional pathways may direct bHR/bLR rats along divergent developmental trajectories and promote a widely different reactivity to the environment.
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