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Tiềm năng bảo vệ của dimethyl fumarate trong mô hình chuột của sự mất myelin thalamocortical
Tóm tắt
Sự thay đổi trong tổ chức tế bào vỏ não, chức năng mạng lưới, cũng như các thiếu sót về nhận thức và vận động gần đây đã được gợi ý là những dấu hiệu bệnh lý trong bệnh xơ cứng đa hệ thống và các mô hình động vật tương ứng, vì chúng có thể xảy ra sau sự mất myelin. Để điều tra những thay đổi chức năng sau sự mất myelin trong một mạng lưới nơ-ron được định nghĩa tốt và tổ chức theo tọa độ, cả in vitro và in vivo, chúng tôi đã tập trung vào vỏ thính giác chính (A1) của chuột trong mô hình cuprizone về sự mất và phục hồi myelin. Sau khi mất myelin trong hệ thống mô hình này, sự lan truyền không-thời gian của các kích thích ở A1 đã bị thay đổi và sự kích hoạt phân cấp của các lớp vỏ não siêu và hạ hạch đã bị mất, cho thấy sự ảnh hưởng sâu sắc đối với mức độ mạng lưới nơ-ron. Ngoài ra, độ trễ phản ứng trong các ghi chép tiềm năng trường và hình ảnh nhuộm nhạy cảm với điện thế đã tăng lên sau khi mất myelin. Những thay đổi này đi kèm với việc mất khả năng phân biệt âm thanh ở các động vật tự do hành vi, giảm lượng protein yếu tố hạt nhân-erythroid 2- có liên quan-2 (Nrf-2) trong nhân tế bào trong nhuộm mô học và vẫn tồn tại trong quá trình phục hồi myelin. Để tìm kiếm các chiến lược mới nhằm khôi phục sự thay đổi mạng lưới do sự mất myelin gây ra bên cạnh quá trình phục hồi myelin đang diễn ra, chúng tôi đã thử nghiệm tiềm năng bảo vệ tế bào của dimethyl fumarate (DMF). Việc điều trị bằng DMF trong quá trình phục hồi myelin đã thay đổi đáng kể sự lan truyền kích thích không-thời gian trong vỏ não, giảm thiểu sự suy giảm nhận thức, và ngăn chặn sự giảm lượng Nrf-2 hạt nhân do mất myelin gây ra. Những kết quả này chỉ ra sự tham gia của các cơ chế chống oxi hóa trong việc điều chỉnh mô hình phản ứng vỏ não không-thời gian sau sự thay đổi trong myelin hóa và chỉ ra DMF như một hợp chất trị liệu cho can thiệp.
Từ khóa
#myelin #xơ cứng đa hệ thống #dimethyl fumarate #tổ chức tế bào vỏ não #chức năng mạng lưới #phục hồi myelinTài liệu tham khảo
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