Cái chết tế bào phát triển trong hệ thống nigrostriatal

Springer Science and Business Media LLC - Tập 318 - Trang 63-72 - 2004
Robert E. Burke1,2
1Department of Neurology, The College of Physicians and Surgeons, Columbia University, New York, USA
2Department of Pathology, The College of Physicians and Surgeons, Columbia University, New York, USA

Tóm tắt

Giống như hầu hết các hệ thống thần kinh, các neuron dopamine ở vùng dưới đồi đen (substantia nigra) trải qua cái chết tế bào tự nhiên theo kiểu chết tế bào chương trình (apoptosis) trong quá trình phát triển. Ở động vật gặm nhấm, hiện tượng này chủ yếu xảy ra sau sinh và diễn ra theo hình thức hai pha với một đỉnh lớn ngay sau khi sinh và một đỉnh nhỏ hơn vào ngày 14 sau sinh. Như đã được lý thuyết thần kinh dinh dưỡng cổ điển hình dung, sự kiện này được điều chỉnh bởi sự tương tác với mục tiêu của các neuron này, đó là vùng đuôi (striatum), vì một tổn thương mục tiêu phát triển dẫn đến sự kiện cái chết tế bào tự nhiên gia tăng với số lượng neuron dopamine ở vùng dưới đồi đen sống sót vào tuổi trưởng thành ít hơn. Cho đến gần đây, các yếu tố thần kinh dinh dưỡng xuất phát từ vùng đuôi cung cấp hỗ trợ phát triển cho các neuron dopamine vẫn chưa được biết đến, nhưng hiện nay có ngày càng nhiều bằng chứng cho thấy yếu tố thần kinh dinh dưỡng do dòng tế bào thần kinh đệm tạo ra (GDNF) đóng vai trò như một yếu tố thần kinh dinh dưỡng giới hạn trong điều kiện sinh lý cho các neuron này trong pha đầu tiên của cái chết tế bào tự nhiên. Trong pha này, việc tiêm GDNF vào trong vùng đuôi làm giảm sự kiện cái chết tế bào tự nhiên và các kháng thể trung hòa làm gia tăng hiện tượng này. Việc biểu hiện quá mức không ngừng của GDNF trong vùng đuôi trong suốt quá trình phát triển ở một mô hình chuột chuyển gen kép độc đáo dẫn đến việc có số lượng neuron dopamine sống sót nhiều hơn trong pha đầu tiên của cái chết tế bào tự nhiên. Tuy nhiên, sự gia tăng này không kéo dài đến tuổi trưởng thành. Do đó, các yếu tố hoặc cơ chế khác phải đóng vai trò quan trọng trong việc xác định số lượng neuron dopamine dưới đồi đen trưởng thành. Việc làm rõ hơn những cơ chế này sẽ rất quan trọng trong việc phát triển các liệu pháp bảo vệ tế bào và thay thế tế bào cho bệnh Parkinson.

Từ khóa

#cái chết tế bào phát triển #neuron dopamine #GDNF #bệnh Parkinson #hệ thống nigrostriatal

Tài liệu tham khảo

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