Furin thúc đẩy hình thành nhánh dendrite và học tập cũng như ghi nhớ ở chuột chuyển gen

Cellular and Molecular Life Sciences - Tập 75 - Trang 2473-2488 - 2018
Binglin Zhu1, Lige Zhao1, Dong Luo1, Demei Xu1, Tao Tan2, Zhifang Dong2, Ying Tang1, Zhuo Min1, Xiaojuan Deng1, Fei Sun3, Zhen Yan4, Guojun Chen1
1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China
2Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
3Department of Physiology, Wayne State University School of Medicine, Detroit, USA
4Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, USA

Tóm tắt

Furin là một protease tiền protein có liên quan đến nhiều quá trình bệnh lý, bao gồm cả các bệnh thoái hóa thần kinh. Tuy nhiên, vai trò của furin trong tính dẻo dai của tế bào thần kinh và học tập, ghi nhớ vẫn chưa được làm rõ. Trong nghiên cứu này, chúng tôi báo cáo rằng ở chuột chuyển gen cụ thể với furin (chuột Furin-Tg), mật độ gai dendrite và sự sinh sản của tế bào gốc thần kinh tăng lên một cách đáng kể. Những con chuột này thể hiện khả năng tăng cường sự tiềm năng dài hạn (LTP) và hiệu suất học tập và ghi nhớ không gian, mà không có sự thay đổi ở các dòng điện hậu synap kích thích/ ức chế mini. Tại vỏ não và hồi hải mã của chuột Furin-Tg, tỷ lệ yếu tố thần kinh có nguồn gốc từ não (mBDNF) trưởng thành so với pro-BDNF, và hoạt động của kinase liên quan đến tín hiệu ngoại bào (ERK) và protein gắn vào yếu tố phản ứng với cAMP (CREB) đều tăng lên một cách đáng kể. Chúng tôi cũng phát hiện rằng giảm CREB trong hồi hải mã làm giảm khả năng tăng cường LTP và chức năng nhận thức ở chuột Furin-Tg. Tóm lại, kết quả của chúng tôi cho thấy rằng furin thúc đẩy sự hình thành morphogenesis dendrite và học tập cũng như ghi nhớ ở chuột chuyển gen, có thể liên quan đến con đường tín hiệu BDNF–ERK–CREB.

Từ khóa

#furin #sự hình thành nhánh dendrite #học tập #ghi nhớ #chuột chuyển gen

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