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

该项目将研究早期生活压力和血清素信号在整个生命周期中的行为之间的相互作用。特别是，它将研究关键时期的发育压力导致通过5HT1A和5HT7受体的5 -羟色胺（5HT）信号平衡的变化，从而影响晚年大脑发育和行为的假设。这一假设是基于大脑发育过程中5HT信号异常作为人类自闭症、精神分裂症、焦虑和抑郁发展的危险因素的报告。在动物实验中，在早期发育过程中对5HT信号的实验操作会导致神经元结构的变化和晚年生活中的行为变化。此外，我们的初步数据表明，发育应激显著影响斑马鱼5HT受体的表达。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激活对5-羟色胺信号通路基因表达的影响，研究发育应激和应激激素受体的激活对大脑发育和行为的影响，探讨以5-羟色胺信号通路为靶点的药物干预是否可以减轻发育应激的影响。特别是通过5HT1A和5HT7受体，可以模拟发育应激对大脑发育和行为的影响，斑马鱼是这个项目的理想模型系统，因为受精和发育发生在外部，容易操纵环境。遗传学（基因表达谱、原位杂交、免疫细胞化学）、药理学（靶向激活或阻断血清素或应激受体信号通路）和行为分析的结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。

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.