A 3Rs platform for glial research: From animal to human to in-silico models

神经胶质研究的 3R 平台：从动物到人类再到计算机模型

• 批准号: NC/X001067/1
• 负责人: Dmitri Rusakov
• 金额: $ 68.42万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FX001067%2F1
• 关键词: 3Rs; platform; glial; research; animal

Passive non-neuronal brain cells called astrocytes have emerged as a critical yet grossly understudied part of brain machinery. Atrocytes take up released neurotransmitters, maintain ionic homeostasis of the extracellular space, and generate a variety of molecular signlas that regulate neural circuit activity. However, the emerging difference between animal and human astroglia in their morphology and physiology threatens the harm-benefit ratio of animal preparations in this important field of neuroscience and neurology. In this respect, realistic computational models of astroglia and astroglia-neuronal networks could provide hypothesis testing, mechanistic physiological insights, and an inter-species knowledge transfer that are unattainable in animal experiments. Exploring such models ought to minimise animal experimentation with no loss of knowledge, yet the methodology to create the corresponding modelling environment is only beginning to emerge. Thus, the present project aims to combine an experimental methodological approach, on the one hand, and open-access computer-simulation platforms, on the other, that would shift the weight of knowledge-based glial research from animals to human tissue preparations and realistic computational models. This will be achieved through the three objectives: (i) to establish working experimental protocols for up-to-date studies of human astroglia in organised brain tissue, making them a commonly accessible, viable alternative to animal brain tissue research strategies, (ii) to create an open-access computational platform that enables exploratory investigation of realistic biophysical models of astroglia, thus reducing similarly aimed experimental trials in animals, and (iii) to generate an experimental data library adaptable for the functional comparison of animal and human astroglia, thus providing a guidance on potentially implausible extrapolation of animal data to human brain astroglia.

被称为星形胶质细胞的被动非神经元脑细胞已成为大脑机制的一个关键但尚未得到充分研究的部分。星形胶质细胞吸收释放的神经递质，维持细胞外空间的离子稳态，并产生多种调节神经回路活动的分子信号。然而，动物和人类星形胶质细胞在形态和生理学上不断出现的差异威胁着动物制剂在神经科学和神经病学这一重要领域中的害益比。在这方面，星形胶质细胞和星形胶质细胞神经元网络的现实计算模型可以提供动物实验中无法实现的假设检验、机械生理学见解和物种间知识转移。探索此类模型应该在不损失知识的情况下最大限度地减少动物实验，但创建相应建模环境的方法才刚刚开始出现。因此，本项目旨在一方面结合实验方法，另一方面结合开放式计算机模拟平台，将基于知识的神经胶质研究的重点从动物转移到人体组织制备和现实研究上。计算模型。这将通过三个目标来实现：（i）为有组织的脑组织中的人类星形胶质细胞的最新研究建立工作实验方案，使它们成为动物脑组织研究策略的普遍可用且可行的替代方案，（ii）创建一个开放式计算平台，能够对星形胶质细胞的现实生物物理模型进行探索性研究，从而减少类似目标的动物实验试验，以及（iii）生成适用于动物和人类星形胶质细胞功能比较的实验数据库，从而提供指导将动物数据推断到人脑星形胶质细胞可能是难以置信的。