Functional implications of focal white matter lesions on neuronal circuits

局灶性白质病变对神经元回路的功能影响

• 批准号: MR/Y014537/1
• 负责人: Ragnhildur Karadottir
• 金额: $ 326.72万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY014537%2F1
• 关键词: Functional; implications; focal; white; matter

Multiple sclerosis (MS) and other neurodegenerative disorders like dementia, Alzheimer's, and Parkinson's disease have a large impact on people's lives and society. There are no fully effective treatments available to stop these diseases from progressing.The human brain is divided into two equal halves: grey and white matter. Most of the research on neurodegenerative disorders has focused on the grey matter of the brain, which contains the neurons, but has overlooked the role of the white matter. New research is showing that lesions within the brain's white matter occur in neurodegenerative disorders. The number of these lesions is linked to problems with thinking and movement. Importantly, these lesions can appear before people experience any symptoms, indicating that these lesions may have a role to play in the disease progression.MS is characterised by white matter lesions in the brain, and from MS research we know that white matter lesions can be repaired, which allows for full symptomatic recovery. This is because in our brain we have specialised stem cells that can repair white matter lesions. Although white matter lesions can be repaired in MS, this regeneration process eventually fails, more so as we age. The failure of repairing white matter lesions can lead the loss of neurons (neurodegeneration), ongoing brain inflammation, and disability.Inflammation in the brain, which is a low-level and ongoing process, is common in both neurodegenerative conditions and MS. Our early results from animal studies suggest that repairing white matter lesions reduces inflammation in both the grey and white matter of the brain. It seems that the failure to repair white matter lesions properly may be causing the ongoing brain inflammation. Our data show that inflammation in the brain and changes in neurons are necessary to trigger white matter repair. This suggests that we need to understand how inflammation, neurons, and white matter lesions interact in order to develop effective treatments, as targeting only one part, like the grey matter or the immune system, may not be enough to prevent further damage.Our research aims to fill this knowledge gap by studying how white matter lesions affect brain function, grey matter inflammation and how repair of white matter lesions is regulated. We hope to learn more about neurodegenerative diseases and whether repairing white matter lesions can reduce brain inflammation, which may be causing the loss of neurons. This research could lead to the development of new treatments that focus on repairing the brain's white matter to preserve brain function. Ultimately, our goal is to reduce the burden of these diseases on individuals, families, and society as a whole.

多发性硬化症 (MS) 和其他神经退行性疾病，如痴呆症、阿尔茨海默病和帕金森病，对人们的生活和社会产生巨大影响。目前还没有完全有效的治疗方法可以阻止这些疾病的进展。人脑分为两个相等的部分：灰质和白质。大多数关于神经退行性疾病的研究都集中在包含神经元的大脑灰质上，但忽视了白质的作用。新的研究表明，大脑白质内的病变发生在神经退行性疾病中。这些病变的数量与思维和运动问题有关。重要的是，这些病变可以在人们出现任何症状之前出现，表明这些病变可能在疾病进展中发挥作用。多发性硬化症的特点是大脑中的白质病变，从多发性硬化症研究中我们知道，白质病变可以与修复，可以使症状完全恢复。这是因为在我们的大脑中，我们有专门的干细胞可以修复白质病变。尽管多发性硬化症中的白质损伤可以得到修复，但这种再生过程最终会失败，随着年龄的增长，情况会更糟。白质病变修复失败可能导致神经元损失（神经退行性变）、持续性脑部炎症和残疾。大脑炎症是一个低水平且持续的过程，在神经​​退行性疾病和多发性硬化症中都很常见。我们的动物研究的早期结果表明，修复白质病变可以减少大脑灰质和白质的炎症。似乎未能正确修复白质病变可能导致持续的脑部炎症。我们的数据表明，大脑炎症和神经元变化对于触发白质修复是必要的。这表明我们需要了解炎症、神经元和白质病变如何相互作用，以便开发有效的治疗方法，因为仅针对灰质或免疫系统等一部分可能不足以防止进一步的损害。我们的研究旨在通过研究白质病变如何影响大脑功能、灰质炎症以及如何调节白质病变的修复来填补这一知识空白。我们希望更多地了解神经退行性疾病，以及修复白质病变是否可以减少可能导致神经元损失的大脑炎症。这项研究可能会导致新疗法的开发，重点是修复大脑白质以保持大脑功能。最终，我们的目标是减轻这些疾病给个人、家庭和整个社会带来的负担。