Chức năng glymphatic bị suy giảm trong giai đoạn đầu của bệnh ở mô hình chuột TDP-43 của bệnh xơ cứng teo cơ một bên

Translational Neurodegeneration - Tập 11 - Trang 1-11 - 2022
Akram Zamani1, Adam K. Walker2, Ben Rollo1, Katie L. Ayers3,4, Raysha Farah1, Terence J. O’Brien1,5, David K. Wright1
1Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
2Queensland Brain Institute, The University of Queensland, St Lucia, Australia
3The Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, Australia
4Department of Pediatrics, The University of Melbourne, Parkville, Australia
5Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia

Tóm tắt

Nhiều bằng chứng cho thấy có thể có sự suy giảm của hệ thống glymphatic trong bệnh xơ cứng teo cơ một bên (ALS). Để điều tra điều này, chúng tôi đã sử dụng chụp cộng hưởng từ (MRI) in vivo để đánh giá chức năng glymphatic ở giai đoạn đầu của bệnh trong một mô hình chuột chuyển gen có sự điều khiển bằng doxycycline (Dox) của biểu hiện TDP-43 người (hTDP-43ΔNLS), điều này mô phỏng bệnh lý chính liên quan đến ALS. Các chuột TDP-43 trưởng thành và chuột đối chứng đơn gen cùng lứa đã được tiến hành MRI đa mô hình theo chiều dài một và ba tuần sau khi ngừng cung cấp Dox, cùng với các đánh giá rotarod hàng tuần về hiệu suất vận động. Chức năng glymphatic được đánh giá bằng cách sử dụng MRI tăng cường tương phản động để theo dõi sự thanh thải của một chất tương phản MR được tiêm vào cisterna magna. So với các đối chứng cùng lứa, chuột TDP-43 cho thấy sự thoái hóa thần kinh tiến triển, bao gồm cả vùng vỏ não vận động chính, vùng vỏ não cảm giác chính và đường dẫn corticospinal, giảm cân đáng kể bao gồm cả sự teo bắp chân, và chiều dài telomere rút ngắn. Hơn nữa, trong sự hiện diện của kiểu hình giống như ALS này, các chuột này có chức năng glymphatic bị rối loạn rõ rệt. Mặc dù mối quan hệ giữa sự thanh thải glymphatic và sự tiến triển của bệnh ALS vẫn chưa được làm sáng tỏ, nhưng những thay đổi này đã xảy ra rất sớm trong quá trình bệnh. Điều này cung cấp bằng chứng ban đầu để gợi ý rằng hệ thống glymphatic có thể là một mục tiêu điều trị tiềm năng trong điều trị ALS.

Từ khóa

#bệnh xơ cứng teo cơ một bên #hệ thống glymphatic #chụp cộng hưởng từ #chuột chuyển gen #thoái hóa thần kinh

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