Determining the impact of early adversity on the developing vertebrate brain

项目摘要 在人类中，儿童和青少年的慢性压力具有长期持续和衰弱的影响， 长大成人童年创伤的受害者更容易患上焦虑症， 创伤后应激障碍（PTSD），药物滥用倾向增加，过度攻击，在某些情况下， 精神疾病，如精神分裂症。尽管童年创伤普遍存在，但人们对 早期生活逆境如何影响大脑的发育和功能。该提案采用了一种新颖的模式 早期生活逆境（ELA）在发育和分子神经发生系统，斑马鱼。我们将 检查ELA对大脑发育的激素，神经元和遗传因素的影响，并研究 他们是如何被ELA改变的这项研究利用了在斑马鱼中建立的强大工具和方法，包括 神经解剖学和神经元活动的全脑成像，糖皮质激素单一化的转基因报告基因， 在多个发育时间点使用CRISPR/Cas9技术进行遗传筛选。由于高 鱼类和人类之间的基因和神经元回路的同源性，我们期待这些发现 从这项研究中揭示了儿童创伤对发育中的大脑有什么生物学影响的关键见解。

PROJECT SUMMARY In humans, chronic stress in children and adolescents has long lasting and debilitating effects that persist well into adulthood. Victims of childhood trauma have increased susceptibility to develop anxiety disorders such as post-traumatic stress (PTSD), increased propensity to substance abuse, hyper-aggression, and, in some cases, psychiatric disorders such as schizophrenia. Despite the prevalence of childhood trauma, little is known about how early life adversity impacts the development and function of the brain. This proposal utilizes a novel model of early life adversity (ELA) in the developmental and molecular neurogenetic system, the zebrafish. We will examine the impacts of ELA on hormonal, neuronal and genetic factors underlying brain development, and study how they are altered by ELA. The study utilizes powerful tools and approaches established in zebrafish, including whole-brain imaging of neuroanatomy and neuronal activity, transgenic reporters of glucocorticoid singling, and genetic screening using CRISPR/Cas9 technology at multiple developmental time points. Because of the high homology of genes and neuronal circuits underlying stress between fish and humans, we expect the findings from this study to reveal critical insight into what biological effects childhood trauma has on the developing brain.