Hành vi xã hội bất thường, tăng hoạt động, giảm trí nhớ không gian xa và tăng cường tín hiệu dopaminergic trung gian D1 ở chuột thiếu gen synthase nitric oxide thần kinh
Tóm tắt
Synthase nitric oxide thần kinh (nNOS) tham gia vào việc điều chỉnh hệ thống thông tin nhắn nội bào đa dạng trong não. Ở người, sự chuyển hóa NOS/nitric oxide bất thường được cho là góp phần vào cơ chế bệnh sinh và bệnh lý học của một số rối loạn tâm thần, như tâm thần phân liệt và rối loạn lưỡng cực. Chuột có đột biến gen nNOS cho thấy hành vi bất thường. Ở đây, chúng tôi đã đưa chuột knockout nNOS (KO) qua một loạt các bài kiểm tra hành vi để điều tra sâu hơn vai trò của nNOS trong các chức năng tâm thần. Chúng tôi cũng kiểm tra vai trò của nNOS trong tín hiệu dopamine/DARPP-32 trong mẫu não của chuột nNOS KO và những tác động của việc tiêm một loại thuốc kích thích thụ thể dopamine D1 lên hành vi ở chuột nNOS KO.
Chuột KO nNOS cho thấy hoạt động tăng cường trong môi trường mới, sự tương tác xã hội tăng lên trong lồng sống của chúng, giảm hành vi liên quan đến trầm cảm và suy giảm khả năng ghi nhớ không gian. Trong mẫu não từ chuột KO nNOS, các tác động của thuốc kích thích thụ thể dopamine D1, SKF81297, lên phosphoryl hóa DARPP-32 và thành phần thụ thể AMPA GluR1 tại các vị trí protein kinase A đã tăng cường. Nhất quán với các kết quả hóa sinh, tiêm bắp một liều thấp SKF81297 đã làm giảm đáng kể sự ức chế trong phản xạ chuẩn bị ở chuột KO nNOS, nhưng không ở chuột kiểu hoang dã.
Các phát hiện này chỉ ra rằng việc thiếu gen nNOS làm tăng cường tín hiệu thụ thể dopamine D1, và gây ra hành vi xã hội bất thường, tăng hoạt động và giảm trí nhớ không gian xa. Chuột KO nNOS có thể được coi là một mô hình động vật độc đáo cho các rối loạn tâm thần.
Từ khóa
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