Thay đổi mức lipid cung cấp bằng chứng cho rối loạn myelin trong thoái hóa thần kinh đa hệ thống

Acta Neuropathologica Communications - Tập 2 - Trang 1-14 - 2014
Anthony S Don1, Jen-Hsiang T Hsiao2, Jonathan M Bleasel2, Timothy A Couttas1, Glenda M Halliday2,3, Woojin Scott Kim2,3
1Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia
2Neuroscience Research Australia, Randwick, Australia
3School of Medical Sciences, University of New South Wales, Sydney, Australia

Tóm tắt

Bệnh thoái hóa thần kinh đa hệ thống (MSA) là một bệnh tiến triển nhanh chóng, được đặc trưng bởi hiện tượng parkinson, loạn điều phối tiểu não và thất bại tự động. Một dấu ấn bệnh lý của MSA là sự hiện diện của các tinh thể α-synuclein trong các tế bào oligodendrocyte, các tế bào hỗ trợ sản xuất myelin trong não. Bệnh lý não và các nghiên cứu trong ống nghiệm chỉ ra rằng sự không ổn định của myelin có thể là một sự kiện sớm trong bệnh sinh của MSA. Lipid là thành phần chính (78% w/w) của myelin và đã được cho là có liên quan đến rối loạn myelin trong MSA. Tuy nhiên, các thay đổi, nếu có, về mức độ/phân phối lipid trong não MSA vẫn chưa được biết đến. Tại đây, chúng tôi thực hiện một phân tích toàn diện về myelin trong MSA. Chúng tôi đã đo lường một cách định lượng ba nhóm lipid, sphingomyelin, sulfatide và galactosylceramide, tất cả đều quan trọng trong tính toàn vẹn và chức năng của myelin, ở các vùng trắng bị ảnh hưởng (dưới vỏ não vận động) và không bị ảnh hưởng (dưới vỏ não thị giác). Đối với cả ba nhóm lipid, phần lớn các loại lipid đều bị giảm nghiêm trọng (40–69%) trong chất trắng bị ảnh hưởng nhưng không bị ảnh hưởng của MSA. Phân tích sự phân bố của các loại lipid cho thấy không có sự thay đổi đáng kể nào trong độ dài/nội dung chuỗi axit béo với MSA. Sự giảm mức lipid đi kèm với sự gia tăng phát biểu của α-synuclein. Những dữ liệu này chỉ ra rằng mức độ tuyệt đối, chứ không phải phân phối, của lipid myelin đã bị thay đổi trong MSA, và cung cấp bằng chứng cho rối loạn lipid myelin trong bệnh lý MSA. Chúng tôi đề xuất rằng sự điều hòa sai lipid myelin trong quá trình bệnh sinh MSA có thể kích thích sự không ổn định của myelin.

Từ khóa

#bệnh thoái hóa thần kinh đa hệ thống #myelin #lipid #α-synuclein #loạn điều phối tiểu não #bệnh lý thần kinh

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