Preservation of criticality in hypoxic, dissociated neural networks, via oestrogen triggered synaptic modulation

通过雌激素触发的突触调节，维持缺氧、分离的神经网络的关键性

• 批准号: 2271004
• 金额: --
• 依托单位: University of Reading
• 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-2271004
• 关键词: Preservation; criticality; hypoxic; dissociated; neural

Billions of interconnected neurons communicate electrically and form activity patterns in a critical state, finely balanced between order and chaos. Criticality is believed to underlie encoding and transferring of information, so it is a fundamental property enabling information processing in the brain but it can be disrupted when a traumatic event, such as an ischemic stroke, occurs. On the other hand, evidence has shown that specific biomolecules, such as oestrogen, can be neuroprotective, during traumatic events.In this project, we will examine how oestrogen can salvage neuronal network activity, under neurodegenerative conditions. We will culture in vitro neural networks on multi-electrode arrays (MEA) and chemically treat them to emulate brain pathology. We will then examine how the structure of the neural networks (synaptic connections) and their activity patterns change under different conditions and investigate the neuroprotective effects of oestrogen. The project will conclude with the proposition of a model that links the transition of neural activity between critical and non-critical states and the mechanism of action of oestrogen. Our long term aim is to identify new strategies for the pharmacological treatment of stroke and other neurodegenerative conditions, harnessing oestrogen's neuroprotective action.

数十亿个相互连接的神经元进行电通信，并在临界状态下形成活动模式，在秩序和混乱之间保持良好的平衡。临界性被认为是信息编码和传输的基础，因此它是大脑进行信息处理的基本属性，但当发生创伤性事件（例如缺血性中风）时，它可能会被破坏。另一方面，有证据表明，特定的生物分子，如雌激素，可以神经保护，在创伤事件中，在这个项目中，我们将研究雌激素如何挽救神经网络的活动，在神经退行性疾病的条件下。我们将在多电极阵列（MEA）上培养体外神经网络，并对其进行化学处理以模拟大脑病理学。然后，我们将研究神经网络的结构（突触连接）及其活动模式在不同条件下的变化，并研究雌激素的神经保护作用。该项目将以一个模型的提议结束，该模型将关键和非关键状态之间的神经活动的转变与雌激素的作用机制联系起来。我们的长期目标是确定新的策略，用于中风和其他神经退行性疾病的药物治疗，利用雌激素的神经保护作用。