Đánh giá tác động hành vi của việc kích hoạt trục HPA mãn tính bằng cách sử dụng chuột biểu hiện quá mức CRH có điều kiện

Springer Science and Business Media LLC - Tập 32 - Trang 815-828 - 2011
Nina Dedic1,2, Chadi Touma1, Cristoph P. Romanowski1, Marcel Schieven3, Claudia Kühne1, Martin Ableitner1, Ailing Lu1, Florian Holsboer3, Wolfgang Wurst2,4,5, Mayumi Kimura1, Jan M. Deussing1
1Max Planck Institute of Psychiatry, Munich, Germany
2Institute of Developmental Genetics, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany
3Max-Planck-Institute of Psychiatry, Munich, Germany
4Lehrstuhl für Entwicklungsgenetik, c/o Helmholtz Zentrum München, Technical University München-Weihenstephan, Neuherberg, Germany
5Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), Standort München, Munich, Germany

Tóm tắt

Hormone giải phóng corticotropin (CRH) và các thụ thể tương ứng của nó đã được liên kết với sinh lý bệnh của các rối loạn liên quan đến stress. Sự bài tiết quá mức CRH trung ương và nồng độ glucocorticoid gia tăng, do sự kiểm soát phản hồi bị suy giảm, đã được chứng minh là đi kèm với các rối loạn tâm trạng và lo âu. Tuy nhiên, việc phân biệt rõ ràng các tác động trực tiếp của CRH được bài tiết quá mức từ các tác động do sự kích hoạt trục HPA gặp khó khăn. Bằng cách áp dụng một chiến lược có điều kiện, chúng tôi đã phát triển hai dòng chuột biểu hiện CRH quá mức: chuột CRH-COE Del biểu hiện CRH toàn thân, trong khi chuột CRH-COE APit biểu hiện CRH một cách chọn lọc ở thùy trước và thùy giữa của tuyến yên. Cả hai dòng chuột đều cho thấy nồng độ corticosterone huyết tương cơ bản tăng và do đó phát triển các dấu hiệu của hội chứng Cushing. Tuy nhiên, trong khi chuột biểu hiện CRH một cách toàn diện cho thấy hành vi lo âu gia tăng, việc biểu hiện CRH tại tuyến yên không gây ra sự thay đổi trong hành vi cảm xúc. Những kết quả này gợi ý rằng tình trạng tăng corticosteroid mãn tính một mình không đủ để làm thay đổi hành vi liên quan đến lo âu mà thực tế là CRH trung ương tăng quá mức tự thân hoặc kết hợp với nồng độ glucocorticoid tăng góp phần vào sự gia tăng hành vi liên quan đến lo âu. Kết luận, các dòng chuột được tạo ra đại diện cho các mô hình động vật quý giá để nghiên cứu hậu quả của việc sản xuất CRH quá mức mãn tính và sự kích hoạt trục HPA.

Từ khóa

#CRH #trục HPA #hành vi lo âu #hội chứng Cushing #mô hình động vật #cortisol

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