催产素逆转猕猴母婴分离负面效应的研究

Above 80% emotionally related disorders have been reported to correlate with early adversity. Thus, studies on effective early interventions of highly importance get more and more focus. In our lab, based on the maternal separation model of rhesus monkeys, we performed positive interventions on the maternal separated monkeys, mainly by increasing sensory stimuli, such as environment enrichment, the presentation of mother monkey related odor stimuli and handling. The results showed that the stress level was reduced in maternal separated infant monkeys and the behavioral abnormalities were reversed. However, the above mentioned intervention was very time-consuming and needed strictly fixed raiser. The present study aims to develop an equally effective intervention through oxytocin. A fundamental study from Yu’s lab found that oxytocin might imitate the increase of sensory stimuli in the early life of the mice. Hence, we hypothesize: brain oxytocin might reduce the stress level through the increase of sensory stimuli, and thus might serve as an effective intervention, to reverse the negative effect brought by maternal separation. Specifically, we plan to investigate the effects of oxytocin invasively inhalation on stress level, and the corresponding changes of neural circuits by fMRI, and thus the behavioral development to testify the impacts of oxytocin on maternal separated infant monkeys. The present study might make very much contribution to the establishment of effective intervention in early adversity related disorders and play an important role in the culture of more than 60,000,000 left-behind-home children in China.

据报道，80%以上的人类情绪相关障碍均与早期逆境相关，所以对其进行干预的研究非常重要。我们实验室通过增加感觉刺激的干预手段降低了母婴分离（早期逆境）小猴的应激水平，逆转了母婴分离造成的行为异常，但是上述干预对实验人员要求非常高，且费时费力。本项目计划发展更加简单有效的催产素干预方法。于翔教授团队发现，脑内给予催产素的效应能够模拟感觉刺激增加的效果。因此，我们假设，给予催产素能够有效增加猕猴的感觉刺激体验，降低应激水平，逆转母婴分离导致的负面效应。具体来说，我们计划通过雾化吸入这种无创的方式给予催产素，考察母婴分离小猴脑脊液催产素水平的变化对其应激水平的影响，进而通过fMRI技术研究其神经环路发育的变化，最终考察行为的发展来证实催产素的效应。本研究将为建立有效的早期干预手段来应对早期逆境相关疾病做出贡献，同时对我国目前6000多万留守儿童的培养具有非常重要的指导意义。

早期逆境对人类的大脑和行为产生长期严重的负面影响。关于有效的早期干预措施的研究越来越受到重视。我们实验室已经成功建立能够充分模拟人类早期逆境长期负面效应的母婴分离猕猴模型。另外，我们通过早期干预，即增加母婴分离小猴的感觉刺激经验（包括丰富环境、母猴气味相关嗅觉刺激呈现以及抚摸），发现其应激水平降低，行为异常被逆转。然而，上述干预措施对实验人员要求非常高，每天干预持续时间相当长。有鉴于此，发展简单有效、同样能够促使感觉刺激经验增加的干预措施非常必要。来自于翔实验室的一项研究发现，给予催产素的效应能够模拟感觉刺激增加的效果，降低应激水平。巧合的是，我们的早期干预小猴脑脊液催产素水平与母婴分离小猴相比显著升高。基于上述基础，我们假设，给予催产素能够有效增加猕猴的感觉刺激经验，从而降低应激水平，逆转母婴分离导致的负面效应。结果发现，催产素能够在一定程度上逆转母婴分离造成的负面效应。本研究对于我国目前6000多万留守儿童的培养具有非常重要的指导意义。