Methamphetamine Gây Mức Độ Neurogenesis Thấp Trong Các Quần Thể Neuron Striatal và Hiệu Suất Vận Động Khác Biệt

Neurotoxicity Research - Tập 26 - Trang 115-129 - 2014
I. K. Tulloch1,2, L. Afanador1,2, L. Baker1, D. Ordonez1, H. Payne1, I. Mexhitaj1, E. Olivares1, A. Chowdhury1, J. A. Angulo1,2
1Department of Biological Sciences, Hunter College, New York, USA
2The Graduate Center of The City University of New York, New York, USA

Tóm tắt

Methamphetamine (METH) gây ra sự mất mát đáng kể một số neuron chiếu và neuron nội tại trong vùng striatum. Gần đây, nhóm nghiên cứu của chúng tôi đã báo cáo về sự tăng sinh của các tế bào mới 36 giờ sau khi tiêm METH, và một số tế bào mới này tồn tại lên đến 12 tuần (Tulloch et al., Neuroscience 193:162–169, 2011b). Chúng tôi giả thuyết rằng một số tế bào này sẽ phân hóa và biểu hiện các kiểu hình neuron striatal. Để kiểm tra giả thuyết này, chuột được tiêm METH (30 mg/kg) và sau đó tiêm một lần BrdU (100 mg/kg) 36 giờ sau khi tiêm METH. Một tuần sau khi tiêm METH, một quần thể tế bào dương tính với BrdU biểu hiện các dấu hiệu của tế bào tổ tiên thần kinh như nestin (18%) và β-III-tubulin (30%). Ở tuần thứ 8, 14% số tế bào dương tính với BrdU cũng dương tính với dấu hiệu của neuron trưởng thành, NeuN. Tại tuần thứ 12, khoảng 7% số tế bào dương tính với BrdU đồng đánh dấu với ChAT, PV hoặc DARPP-32. Chúng tôi đã đo lường sự phối hợp vận động trên thiết bị rotarod và hoạt động tâm lý vận động trong môi trường mở. Tại tuần thứ 12, chuột được tiêm METH thể hiện sự thiếu hụt phối hợp vận động chậm trễ. Ngược lại, các bài kiểm tra trong môi trường mở tiết lộ rằng chuột được tiêm METH so với chuột tiêm dung dịch muối có sự thiếu hụt tâm lý vận động ở 2.5 ngày nhưng không ở 2 tuần hoặc hơn sau khi tiêm METH. Tổng hợp lại, các dữ liệu này chứng minh rằng một số tế bào mới được sinh ra trong vùng striatum phân hóa và biểu hiện các kiểu hình của neuron striatal. Tuy nhiên, tỷ lệ của những neuron mới này thấp so với tỷ lệ bị chết do apoptosis 24 giờ sau khi tiêm METH. Cần có thêm nhiều nghiên cứu để xác định xem các neuron mới này có chức năng hay không.

Từ khóa

#methamphetamine #neurogenesis #striatal neurons #neuronal phenotypes #motor coordination

Tài liệu tham khảo

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