The role of the immune system in mediating the effect of chronic stress on adult hippocampal neurogenesis

免疫系统在介导慢性应激对成人海马神经发生的影响中的作用

• 批准号: 2309098
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2309098
• 关键词: role; immune; system; mediating; effect

Egg consumers are becoming increasingly concerned with animal welfare, leading to an incentive for egg producers to favour free-range or open-barn housing systems for laying hens. However, the increased mobility of hens in cage-free systems may cause welfare problems such as injury and infection that may additionally lead to reduced egg production efficiency. It is therefore important to understand the environmental factors that may induce chronic stress in laying hens and the physiological mechanisms involved.Our lab is currently investigating the use of adult hippocampal neurogenesis (AHN) as a tool to monitor chronic stress in poultry. We have demonstrated that fewer new neurons are produced in the hippocampus brain region when hens experience chronic stress induced experimentally over a period of weeks. However, the physiological mechanisms signalling chronic stress to the brain are not well understood. The secretion of adrenal glucocorticoid hormones is widely studied in birds and mammals as a protective response to acute and chronic environmental stressors. However, in mammals, increased glucocorticoid secretion can be associated both with decreased and increased neurogenesis in response to negative and positive stimuli, respectively. Therefore, there is a need to investigate other signals as possible mediators of the effects of chronic stress on the brain. It is known from biomedical research that chronic inflammation is a common factor in stress-related disease and that inflammatory cytokines may be important mediators of neurogenesis. However this has not been investigated in birds, including poultry. This project will therefore investigate the role of the immune response in mediating the effect of chronic stress on AHN in laying hens. As a first step, we will measure the gene expression in the immune system of a variety of pro- and anti-inflammatory cytokine molecules and their receptors in brain and spleen tissue collected during some of our previous studies of chronic stress in laying hens. These include experimental induction of unpredictable chronic mild stress (UCMS), comparison of commercial caged and free-range housing systems, and investigation of birds in commercial flocks with naturally-occurring severe footpad dermatitis that may cause chronic pain. We will relate the quantification of immune system gene expression to our measures of neurogenesis in individual birds with the aim of identifying immune system markers that are linked to decreased neurogenesis.Once we have identified cytokine-related marker genes associated with chronic stress we will investigate experimentally the link between the immune system and chronic stress in collaboration with our Liverpool partner. We plan a 2x2 experimental design comprising two groups of hens subjected to UCMS or a pro- or anti-inflammatory treatment, with two respective control groups. We predict that the experimental treatments will alter AHN and the expression of pro-inflammatory marker genes. Changes in gut microbiota will also be assessed in the experiment. This will establish a possible link between inflammatory signals produced by specific gut microbe taxa and reduced neurogenesis. This provides an opportunity for a further study to investigate the effects of changing the gut flora composition (for example by faecal transplantation) in promoting resilience to chronic stress by reduced production of inflammatory signals. Overall, the project will contribute to basic understanding in birds of the link between chronic stress and the immune system. More specifically it will allow the identification of molecular markers of chronic stress in laying hens that can be monitored in industrial settings to evaluate the effect on welfare of housing and other production conditions. Establishing a link between gut microbiota and immune signalling to the brain may allow the development of methods to manipulate the gut flora that could be implemented in industry.

鸡蛋消费者越来越关注动物福利，这导致鸡蛋生产商倾向于采用自由放养或露天谷仓的蛋鸡饲养制度。然而，在非笼养系统中，母鸡流动性的增加可能会导致诸如伤害和感染等福利问题，这可能还会导致鸡蛋生产效率的降低。因此，了解可能导致蛋鸡慢性应激的环境因素及其涉及的生理机制是很重要的。我们的实验室目前正在研究使用成年海马神经发生(AHN)作为监测家禽慢性应激的工具。我们已经证明，当母鸡在几周内经历实验诱导的慢性应激时，在海马区产生的新神经元较少。然而，向大脑发出慢性应激信号的生理机制还不是很清楚。肾上腺糖皮质激素的分泌在鸟类和哺乳动物中被广泛研究，作为对急性和慢性环境应激源的保护性反应。然而，在哺乳动物中，糖皮质激素分泌的增加可以分别与对消极刺激和积极刺激反应的神经发生减少和增加相关。因此，有必要研究其他信号，作为慢性应激对大脑影响的可能中介。生物医学研究表明，慢性炎症是应激相关疾病的常见因素，炎性细胞因子可能是神经发生的重要介质。然而，这还没有在包括家禽在内的禽类中进行调查。因此，本项目将研究免疫反应在调节慢性应激对产蛋母鸡AHN影响中的作用。作为第一步，我们将测量免疫系统中各种促炎和抗炎细胞因子分子及其受体在脑和脾组织中的基因表达，这些受体是在我们之前对蛋鸡慢性应激的一些研究中收集的。这些措施包括不可预测的慢性轻度应激(UCMS)的实验性诱导，商业笼养和自由放养住房系统的比较，以及对商业鸡群中患有可能导致慢性疼痛的自然发生的严重足垫皮炎的鸟类的调查。我们将把免疫系统基因表达的量化与我们对单个鸟类神经发生的测量联系起来，目的是识别与神经再生减少有关的免疫系统标记。一旦我们确定了与慢性应激相关的细胞因子相关标记基因，我们将与利物浦的合作伙伴合作，从实验上研究免疫系统和慢性应激之间的联系。我们计划了一个2x2的实验设计，包括两组接受UCMS或促炎或抗炎治疗的母鸡，以及两个相应的对照组。我们预测，实验性治疗将改变ANN和促炎标记基因的表达。肠道微生物区系的变化也将在实验中进行评估。这将在特定肠道微生物类群产生的炎症信号和减少的神经发生之间建立可能的联系。这为进一步研究改变肠道菌群组成(例如通过粪便移植)通过减少炎症信号的产生来提高对慢性应激的弹性提供了机会。总体而言，该项目将有助于鸟类对慢性应激和免疫系统之间的联系的基本了解。更具体地说，它将允许识别蛋鸡慢性应激的分子标记，可以在工业环境中进行监测，以评估对住房和其他生产条件的福利的影响。建立肠道微生物区系和大脑免疫信号之间的联系，可能会开发出可以在工业上实施的操纵肠道菌群的方法。