Hippocampal Gene Expression in bred High Responder (bHR) vs. bred Low Responder (bLR) Rats: RNA-Seq Data from Generation F29

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 RNA-sequencing study examined gene expression in the hippocampus, a region critical for emotional regulation, in generation F29 male bHR rats and bLR rats from two ages: P14 and adulthood (n=2/group).学界普遍认为，精神障碍间显著的共病模式，源自一系列潜在易感性谱系，该谱系由遗传风险与应激、童年逆境等环境因素的复杂交互作用共同塑造。 该谱系的一端为内化障碍（internalizing disorders），与神经质、焦虑及抑郁相关；谱系另一端则为外化障碍（externalizing disorders），与冒险行为及求新倾向相关，这类特征可见于躁狂症、物质滥用及冲动控制障碍患者中。 本研究通过对新型环境反应存在差异的大鼠开展选择性繁育，以此建模该谱系两端行为背后的遗传贡献机制。 “繁育高反应型（Bred high responder, bHR）”大鼠具有高度探索性，且表现出去抑制、求新的气质特征，包括多动、攻击行为及觅药行为；“繁育低反应型（Bred low responder, bLR）”大鼠则呈高度抑制状态，运动活动减少，并表现出焦虑样与抑郁样行为。 这些行为倾向稳定且持久，于发育早期即可显现，与人类的气质特质类似。 本项RNA测序（RNA-sequencing）研究检测了第29代（F29）雄性bHR与bLR大鼠海马体（hippocampus，情绪调控的关键脑区）的基因表达水平，受试大鼠分为两个年龄组：出生后第14天（P14）及成年期，每组n=2只。