Tác động của Ketamine trong Chữa trị Trầm cảm Không liên quan đến Chuyển hóa 18F-FDG hoặc Sự Miễn dịch Tyrosine Hydroxylase tại Khu vực Dưới Não Tạng của Chuột Wistar

Neurochemical Research - Tập 40 - Trang 1153-1164 - 2015
Pedro Porto Alegre Baptista1, Lisiani Saur1, Pamela Bambrilla Bagatini1, Samuel Greggio2, Gianina Teribele Venturin2, Sabrina Pereira Vaz1, Kelly dos Reis Ferreira1, Juliana Silva Junqueira1, Diogo Rizzato Lara1, Jaderson Costa DaCosta2, Cristina Maria Moriguchi Jeckel2, Régis Gemerasca Mestriner1, Léder Leal Xavier1,2
1Laboratório de Biologia Celular e Tecidual e Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Ciências Morfofisiológicas, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
2Centro de Pesquisa Pré-Clínica e Centro de Produção de Radiofármacos, Instituto do Cérebro do Rio Grande do Sul – INSCER-PUCRS, Porto Alegre, Brazil

Tóm tắt

Rối loạn trầm cảm lớn (MDD) là một vấn đề sức khỏe quan trọng thường liên quan đến căng thẳng. Một trong những vùng não chính liên quan đến MDD là khu vực dưới não tạng (VTA), một trung tâm dopaminergic, là phần của mạch phần thưởng và động lực. Các nghiên cứu gần đây cho thấy sự thay đổi ở các nơron dopaminergic VTA có liên quan đến trầm cảm và điều trị. Ketamine đã cho thấy tác dụng chống trầm cảm nhanh, mạnh mẽ ở liều dưới gây mê. Vì vậy, mục tiêu của nghiên cứu là làm rõ liệu ketamine có thể đảo ngược hành vi trầm cảm giống như do giao thức stress không thể đoán trước mãn tính (CUS) gây ra hay không, và liệu nó có thể gây ra sự thay đổi về chuyển hóa và sự miễn dịch của tyrosine hydroxylase (TH) ở VTA hay không. Để thực hiện điều này, 48 con chuột Wistar đã được chia thành bốn nhóm: kiểm soát + dung dịch muối (CTRL + SAL), kiểm soát + ketamine (CTRL + KET), CUS + dung dịch muối (CUS + SAL), CUS + ketamine (CUS + KET). Các nhóm CUS đã trải qua 28 ngày giao thức CUS. Dung dịch muối hoặc ketamine (10 mg/kg) được tiêm dưới phúc mạc một lần vào ngày 28. Hành vi được đánh giá thông qua bài kiểm tra sự ưa thích sucrose, bài kiểm tra trường mở, và bài kiểm tra bơi cưỡng bức. Chuyển hóa glucose trong não được đánh giá và định lượng bằng microPET. Sự miễn dịch TH được đánh giá bằng cách ước tính mật độ nơron và mật độ quang học khu vực và tế bào. Sự giảm lượng sucrose tiêu thụ ở các nhóm CUS và sự gia tăng bất động đã nhanh chóng được đảo ngược bởi ketamine (p < 0,05). Không có sự khác biệt nào được quan sát thấy trong bài kiểm tra trường mở. Không có sự thay đổi nào đối với chuyển hóa VTA và phản ứng miễn dịch TH. Những kết quả này cho thấy hành vi giống như trầm cảm do CUS gây ra và tác dụng chống trầm cảm của ketamine không liên quan đến những thay đổi trong chuyển hóa nơron hoặc sản xuất dopamine ở VTA.

Từ khóa

#Rối loạn trầm cảm lớn #Ketamine #VTA #Tyrosine Hydroxylase #Stress không thể đoán trước #Hành vi trầm cảm.

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