生物谷報道：精神活性物質成癮防治和戒除是本世紀人類面臨的重大難題,，也是近年來國際毒理學和心理學研究的熱點方向,。然而,，這一領域的關鍵性問題之一——精神活性物質成癮過程中的突觸形態(tài)異常和神經生理改變的潛在分子機制不能得到準確描述，大大影響了該領域的科學進展,。日前浙江大學沃森基因組科學研究院朱永平教授的博士生楊柳與中科院心理所行為遺傳中心孫中生教授就這一問題展開合作,，取得重要成果。本研究建立了慢性嗎啡成癮的大鼠模型來模擬人類慢性成癮過程,，并使用雙向電泳和質譜來分析前額葉皮質突觸相關蛋白在成癮的各個階段的差異改變,，試圖找出與成癮各階段相關的生物學分子標記物。研究結果表明,，包括能量代謝,、信號轉導、突觸傳遞,、骨架蛋白,、分子伴侶和突觸蛋白合成器在內的6類80個差異蛋白構成了嗎啡誘導的依賴、戒斷和復燃的突觸相關分子網絡,。這一結論描述并揭示了慢性嗎啡暴露引起的復雜,、綜合的神經性適應過程，為毒品防治和戒除類藥物的開發(fā)提供新的科學依據,。
研究論文《Proteomic Analysis of Rat Prefrontal Cortex in Three Phases of Morphine-Induced Conditioned Place Preference（嗎啡誘導條件性位置偏愛三個階段大鼠前額葉皮質的蛋白質組學分析）》已在蛋白質組學領域的國際頂尖雜志《蛋白質組學研究》（Journal of Proteome Research） 07年4月20日的刊號上全文發(fā)表,。
原始出處:
J. Proteome Res., ASAP Article 10.1021/pr060649o S1535-3893(06)00649-X
Web Release Date: April 20, 2007 Copyright © 2007 American Chemical Society
Proteomic Analysis of Rat Prefrontal Cortex in Three Phases of Morphine-Induced Conditioned Place Preference
Liu Yang, Zhong Sheng Sun, and Yong-ping Zhu*
James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China, Department of Toxicology, Zhejiang University, School of Medicine, Hangzhou, Zhejiang, P. R. China, and Behavioral Genetics Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, P. R. China
Received December 6, 2006
Abstract:
Morphological alterations of synapse are found after morphine administration, suggesting that regulation of synaptic plasticity may be one of the mechanisms of neuroadaptation in addiction. However, the molecular basis underlying the abnormal synapse morphological and physiological changes in the morphine-induced dependence, withdraw, and relapse is not well understood. As prefrontal cortex (PFC) is one of the most important brain regions, which provides executive control over drug use and is severely impaired in many addicts, systematic analysis of the biochemical and molecular alteration of synaptic fraction of PFC in morphine-induced neuroadaptation is necessary. In this study, differential protein expression profiling of synaptic fraction of rat PFC based on morphine-induced conditioned place preference (CPP) model was performed with two-dimensional gel electrophoresis (2-DE). Our results showed that a total of 80 proteins were differentially expressed by 2-DE analysis during three phases of CPP assay. Of them, 58 were further identified by mass spectrometry. These proteins were classified into multiple categories, such as energy metabolism, signal transduction, synaptic transmission, cytoskeletal proteins, chaperones, and local synaptic protein synthetic machinery according to their biological functions. Our study provides a global view of synaptic-related molecular networking in PFC under morphine-induced dependence, withdraw, and relapse, indicative of a concerted biological process in neuroadaptation under chronic morphine exposure.
Keywords: morphine addiction conditioned place preference (CPP) prefrontal cortex (PFC) proteomics neuroplasticity
