Profiling neurodegeneration of sensory systems in multiple sclerosis

多发性硬化症中感觉系统的神经变性分析

• 批准号: 513877247
• 负责人: Professor Dr. Manuel A. Friese
• 金额: --
• 依托单位: Neurologische Klinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/513877247?language=en
• 关键词: Profiling; neurodegeneration; sensory; systems; multiple

Neurodegeneration in multiple sclerosis (MS) follows a particular spatial distribution with some brain regions and neuronal subtypes being more affected than others. The visual and olfactory system are commonly disturbed in MS and its animal model experimental autoimmune encephalomyelitis (EAE), resulting in sensory deficits. However, the underlying intrinsic properties that put neurons at risk for degeneration are still incompletely understood. As sensory systems are ideal representative regions to identify shared pathways that determine neuronal injury during inflammation, we propose to leverage olfactory bulb and retina samples to explore the principles of differential neuronal vulnerability in MS. Therefore, we will analyze transcriptional profiles of neuronal nuclei from both human MS tissue and different stages of EAE mouse models in comparison to appropriate controls. By using droplet based single cell RNA sequencing we will identify vulnerable neuron subtypes and use neuronal in vitro systems to explore targetable candidates to reinforce susceptible neuronal populations. This approach will advance our understanding of neuronal loss in MS and deliver new therapeutic angles to counteract neurodegeneration.

多发性硬化症 (MS) 中的神经变性遵循特定的空间分布，某些大脑区域和神经元亚型比其他区域受到的影响更大。 MS及其动物模型实验性自身免疫性脑脊髓炎（EAE）的视觉和嗅觉系统通常受到干扰，导致感觉缺陷。然而，使神经元面临退化风险的潜在内在特性仍不完全清楚。由于感觉系统是确定炎症期间确定神经元损伤的共享途径的理想代表区域，因此我们建议利用嗅球和视网膜样本来探索多发性硬化症中不同神经元脆弱性的原理。因此，我们将分析人类 MS 组织和 EAE 小鼠模型不同阶段的神经元核的转录谱，并与适当的对照进行比较。通过使用基于液滴的单细胞 RNA 测序，我们将识别脆弱的神经元亚型，并使用神经元体外系统来探索可靶向的候选物，以增强易受影响的神经元群体。这种方法将增进我们对多发性硬化症中神经元丢失的理解，并提供新的治疗角度来对抗神经退行性变。