Hippocampal Gene Expression in bred High Responder (bHR) vs. bred Low Responder (bLR) Rats: Illumina Microarray Data from Generation F15

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 Illumina (RatRef-12v1 Beadchip) microarray study examined gene expression in the hippocampus in generation F15 male bHR rats and bLR rats at age postnatal day 14 (P14, n=6 per group).学界普遍认为，精神障碍间显著的共病模式源于一系列潜在易感性谱（spectrum of latent liability），该谱由遗传风险与应激、童年逆境等环境因素的复杂交互作用共同塑造。该谱的一端为内化性障碍（internalizing disorders），与神经质、焦虑及抑郁症状相关；谱的另一端则为外化性障碍（externalizing disorders），与冒险行为、求新倾向相关，可见于躁狂、物质滥用及冲动控制障碍等病症。本研究通过对新奇环境反应存在差异的大鼠开展选择性繁育，以此构建该易感性谱两端的遗传贡献模型。其中，繁育高反应型（Bred high responder, bHR）大鼠具有高度探索性，表现出脱抑制、求新的气质特征，包括多动、攻击行为及药物觅求行为；繁育低反应型（Bred low responder, bLR）大鼠则表现出高度抑制性，伴随运动活动降低、焦虑及类抑郁行为。这些行为倾向稳定且持久，其发育起始早，与人类的气质形成过程相似。本研究采用因美纳（Illumina）RatRef-12v1 Beadchip芯片进行微阵列分析，检测了第15代（F15）雄性bHR与bLR大鼠在出生后第14天（P14，每组n=6）的海马体基因表达水平。