Luchetti Alessandra, Oddi Diego, Lampis Valentina, Centofante Eleonora, Felsani Armando, Battaglia Marco, D'Amato Francesca R
Institute of Cell Biology and Neurobiology, National Research Council/Fondazione Santa Lucia Rome, Italy.
Academic Centre for the Study of Behavioral Plasticity, Vita-Salute San Raffaele University Milan, Italy.
Front Behav Neurosci. 2015 Apr 21;9:93. doi: 10.3389/fnbeh.2015.00093. eCollection 2015.
Early life events have a crucial role in programming the individual phenotype and exposure to traumatic experiences during infancy can increase later risk for a variety of neuropsychiatric conditions, including mood and anxiety disorders. Animal models of postnatal stress have been developed in rodents to explore molecular mechanisms responsible for the observed short and long lasting neurobiological effects of such manipulations. The main aim of this study was to compare the behavioral and hormonal phenotype of young and adult animals exposed to different postnatal treatments. Outbred mice were exposed to (i) the classical Handling protocol (H: 15 min-day of separation from the mother from day 1 to 14 of life) or to (ii) a Repeated Cross-Fostering protocol (RCF: adoption of litters from day 1 to 4 of life by different dams). Handled mice received more maternal care in infancy and showed the already described reduced emotionality at adulthood. Repeated cross fostered animals did not differ for maternal care received, but showed enhanced sensitivity to separation from the mother in infancy and altered respiratory response to 6% CO2 in breathing air in comparison with controls. Abnormal respiratory responses to hypercapnia are commonly found among humans with panic disorders (PD), and point to RCF-induced instability of the early environment as a valid developmental model for PD. The comparisons between short- and long-term effects of postnatal handling vs. RCF indicate that different types of early adversities are associated with different behavioral profiles, and evoke psychopathologies that can be distinguished according to the neurobiological systems disrupted by early-life manipulations.
早期生活事件在塑造个体表型方面起着关键作用,婴儿期经历创伤性事件会增加日后患多种神经精神疾病的风险,包括情绪和焦虑障碍。在啮齿动物中已建立产后应激的动物模型,以探索导致此类操作所观察到的短期和长期神经生物学效应的分子机制。本研究的主要目的是比较接受不同产后处理的幼年和成年动物的行为和激素表型。远交群小鼠被暴露于(i)经典的抚触方案(H:从出生第1天到第14天,每天与母亲分离15分钟)或(ii)重复交叉寄养方案(RCF:从出生第1天到第4天,由不同的母鼠收养一窝幼崽)。接受抚触的小鼠在婴儿期得到更多的母性关怀,并且在成年期表现出已被描述的情绪反应降低。重复交叉寄养的动物在接受的母性关怀方面没有差异,但与对照组相比,它们在婴儿期表现出对与母亲分离的敏感性增强,并且对呼吸空气中6%二氧化碳的呼吸反应发生改变。对高碳酸血症的异常呼吸反应在患有惊恐障碍(PD)的人类中很常见,这表明RCF诱导的早期环境不稳定是PD的一种有效的发育模型。产后抚触与RCF的短期和长期效应之间的比较表明,不同类型的早期逆境与不同的行为特征相关,并引发可根据早期生活操作所破坏的神经生物学系统来区分的精神病理学。