在Sanfilippo疾病中严重的中枢神经系统脱髓化
Mahsa Taherzadeh1,2, Erjun Zhang1, Irene Londono1
1Department of Pediatrics, Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Centre, University of Montreal, Montreal, QC, Canada.
Frontiers in molecular neuroscience
|January 1, 2024
概括
粘多糖症III (MPS III) 引起神经炎症和白质损伤,影响髓和轴突. 磁力共振成像显示出脱髓化和组织损失,这表明它可以用于监测MPS III进展.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生化学
- 医疗成像医学成像
背景情况:
- 神经性溶解体储存疾病,如粘多糖糖症III (MPS III或Sanfilippo疾病),以慢性渐进的神经炎症为特征.
- 神经炎症与白质通道病理密切相关,影响轴突髓和整体大脑结构.
研究的目的:
- 在MPS IIIC (Hgsnat-/-) 的小鼠模型和人类MPS III患者的死后脑样本中研究轴突髓化和白质密度.
- 确定MPS III中疾病进展和治疗反应的潜在的非侵入性成像生物标志物.
主要方法:
- 来自MPS III患者和Hgsnat-/-小鼠的大脑和脊髓组织的免疫光分析,以评估髓蛋白,储存材料和微.
- 体 (CC) 的传输电子显微镜,以评估轴突髓化和寡细胞形态.
- 在老鼠大脑上使用扩散基谱成像 (DSI) 来分析白质完整性.
主要成果:
- 在MPS III小鼠和患者中观察到肌相关蛋白 (MBP,MAG,MOG) 的水平降低.
- 超结构分析揭示了骨髓膜的破坏,骨髓厚度的减少,以及稀缺的骨髓细胞,其中含有储存材料的放大溶解体.
- 扩散基谱成像显示MPS III小鼠的CC中显著的脱髓化 (增加辐射扩散性) 和组织损失 (增加阻碍扩散性).
结论:
- 白质损伤在MPS III的病理生理学中起着重要作用.
- 磁力共振成像 (MRI),特别是DSI,通过检测脱髓化和组织损失,显示出作为评估MPS III疾病进展和治疗疗效的非侵入性工具的前景.
相关概念视频
01:25Nervous Tissue: Myelin
The myelin sheath is a multilayered lipid and protein covering that insulates the axon of a neuron, enhancing the speed of nerve impulse conduction. Axons without this sheath are referred to as unmyelinated. Two types of neuroglia, Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS) are responsible for producing myelin sheaths.
Schwann cells begin to form myelin sheaths around axons during fetal development. They wrap around a small...
Schwann cells begin to form myelin sheaths around axons during fetal development. They wrap around a small...
01:26Rocky Mountain Spotted Fever
Rocky Mountain Spotted Fever (RMSF) is a severe tick-borne illness caused by Rickettsia rickettsii, a Gram-negative, coccobacillary bacterium. This pathogen is an obligate intracellular parasite, requiring a host cell for replication. Transmission occurs through the bite of an infected tick. In the United States, the most important vectors are Dermacentor variabilis (American dog tick) and Dermacentor andersoni (Rocky Mountain wood tick), though other tick species may also serve as vectors.
01:17Poliomyelitis
Poliomyelitis is caused by poliovirus, a small, non-enveloped, positive-sense RNA virus of the Picornaviridae family and Enterovirus genus. Transmission occurs primarily via the fecal-oral route, often through ingestion of contaminated water or food. The virus initially replicates in the oropharynx and intestinal mucosa, particularly in lymphoid tissues such as the tonsils, Peyer’s patches, and regional lymph nodes. Primary viremia follows, allowing dissemination throughout the body.In most...
01:26Encephalitis ll: Pathophysiology
Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.Autoimmune EncephalitisIn autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can...
01:19Multiple Sclerosis l: Introduction
Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...