Các đặc điểm bệnh lý thần kinh và hành vi của mô hình chuyển gen APP/PS1/MAPT (6xTg) của bệnh Alzheimer

Molecular Brain - Tập 15 - Trang 1-13 - 2022
Sung Hyun Tag1,2, Baeksun Kim1,2, Jinhee Bae1, Keun-A Chang3,4,5, Heh-In Im1,2
1Convergence Research Center for Brain Science, Korea Institute of Science & Technology (KIST), Seoul, Republic of Korea
2Division of Bio-Med (Neuroscience), KIST School, Korea University of Science & Technology (UST), Seoul, Republic of Korea
3Department of Pharmacology, College of Medicine, Gachon University, Incheon, Republic of Korea
4Neuroscience Research Institute, Gachon University, Incheon, Republic of Korea
5Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, Republic of Korea

Tóm tắt

Bệnh Alzheimer liên quan đến nhiều rối loạn chức năng não, bao gồm suy giảm trí nhớ, mất tế bào thần kinh, kích hoạt tế bào hình sao, mảng amyloid-β và các búi sợi thần kinh. Các mô hình động vật chuyển gen của bệnh Alzheimer đã chứng tỏ giá trị vô giá trong nghiên cứu cơ bản về bệnh này. Tuy nhiên, các mô hình chuột Alzheimer đã được phát triển cho đến nay vẫn chưa tái hiện đầy đủ các đặc điểm bệnh lý và hành vi tương tự như bệnh Alzheimer ở người. Ở đây, chúng tôi đã điều tra các di chứng thần kinh - hành vi trong mô hình chuột 6xTg mới của bệnh Alzheimer, được phát triển bằng cách tích hợp đột biến P301L trong protein tau của con người vào mô hình chuột 5xFAD, một mô hình phổ biến của bệnh Alzheimer. Ở tuổi 11 tháng, chuột 6xTg thể hiện các quá trình bệnh lý cốt lõi của bệnh Alzheimer, bao gồm sự tích tụ mảng amyloid-β, mất tế bào thần kinh rộng rãi, mức độ kích hoạt tế bào hình sao tăng cao và phosphoryl hóa tau bất thường trong não. Từ 9 đến 11 tháng tuổi, chuột 6xTg đã biểu hiện cả những suy giảm hành vi nhận thức và phi nhận thức liên quan đến bệnh Alzheimer, bao gồm mất trí nhớ, tăng cường hoạt động, hành vi lo âu, hành vi tương tự trầm cảm và giảm khả năng kiểm soát nhận thức cảm giác. Dữ liệu của chúng tôi gợi ý rằng mô hình chuột 6xTg của bệnh Alzheimer ở tuổi tác có những đặc điểm bệnh lý và hành vi nhận thức tương tự như bệnh Alzheimer ở người. Do đó, mô hình chuột 6xTg có thể là một mô hình quý giá để nghiên cứu các hành vi không nhận thức liên quan đến bệnh Alzheimer.

Từ khóa

#Bệnh Alzheimer #mô hình chuột 6xTg #rối loạn thần kinh #hành vi #suy giảm trí nhớ

Tài liệu tham khảo

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