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The effect of early life stress on serotonin signalling-related gene expression in zebrafish

早期生活应激对斑马鱼血清素信号相关基因表达的影响

基本信息

批准号：
2098625
负责人：
金额：
--
依托单位：
University of Leicester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2098625
关键词：
effect early life stress serotonin

项目摘要

This project will investigate the interaction between early life stress and serotonergic signalling on behaviour across the life-span. In particular it will study the hypothesis that developmental stress during critical periods results in changes in the balance of serotonin (5HT) signalling via 5HT1A and 5HT7 receptors, affecting brain development and behaviour in later life. The hypothesis is based on reports of abnormalities in 5HT signalling during brain development as risk factors for the development of autism, schizophrenia, anxiety and depression in humans. In animals, experimental manipulations of 5HT signalling during early development cause changes in the neuronal architecture and behavioural changes in later life. Furthermore, our preliminary data has shown that developmental stress significantly affects 5HT receptor expression in zebrafish.The main objectives of the project are: To study the effects of developmental stress or pharmacological activation of stress hormone receptors on the expression 5-HT signalling pathway genes To characterise the effects of developmental stress and stress hormone receptor activation on brain development and behaviour To explore whether pharmacological interventions targeting 5-HT signalling can mitigate the effects of developmental stress To investigate whether pharmacological disruption of serotonin signalling, especially via 5HT1A and 5HT7 receptors, can mimic the effects of developmental stress on brain development and behaviourZebrafish are an ideal model system for this project as fertilisation and development occur externally enabling easy manipulation of the environment. A combination of genetic (gene expression profiling, in situ hybridisation, immunocytochemistry), pharmacological (targeted activation or blocking of serotonin or stress receptor signalling pathways) and behavioural assays will be used to study the interactions between early life stress, serotonin signalling, brain development and behaviour.

该项目将研究早期生活压力和整个生命周期中行为的神经递质信号之间的相互作用。特别是它将研究的假设，即在关键时期的发展压力的结果在5羟色胺（5 HT）信号通过5 HT 1A和5 HT 7受体的平衡的变化，影响大脑发育和行为在以后的生活。这一假说是基于大脑发育过程中5 HT信号异常的报告，这些异常是人类自闭症、精神分裂症、焦虑和抑郁症发展的风险因素。在动物中，在早期发育过程中对5 HT信号的实验操作会导致神经元结构的变化和以后生活中的行为变化。此外，我们的初步数据表明，发育应激显著影响斑马鱼的5 HT受体表达。该项目的主要目标是：研究发育应激或应激激素受体的药理学激活对5-HT信号通路基因研究发育应激和应激激素受体激活对脑发育和行为的影响，探讨是否靶向5-HT信号传导的药理学干预可以减轻发育应激的影响。为了研究5-羟色胺信号传导的药理学破坏，特别是通过5 HT 1A和5 HT 7受体，斑马鱼是该项目的理想模型系统，因为受精和发育发生在外部，使得能够容易地操纵大脑发育和行为。环境遗传（基因表达谱，原位杂交，免疫细胞化学），药理学（有针对性的激活或阻断血清素或应激受体信号通路）和行为分析的组合将用于研究早期生活压力，血清素信号，大脑发育和行为之间的相互作用。