Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine.
Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine.
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蛋白质组学分析在退出吗啡后六个月后揭示了大鼠脑中细胞骨架和突触可塑性相关的蛋白的表达变化。
DOI：
10.3390/life11070683
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发表时间：
2021-07-13
期刊：
影响因子：
--
通讯作者：
Novotny J
中科院分区：
文献类型：
--
作者：
Drastichova Z;Hejnova L;Moravcova R;Novotny J
药物戒断与戒断症状有关，包括认知功能缺陷，即使在长期停药后，这些症状也可能持续存在。认知缺陷至少部分是由突触可塑性的改变引起的，但精确的分子机制尚未完全确定。在本研究中，通过无标记定量（LFQ）蛋白质组分析测定了停止吗啡慢性治疗六个月后戒断大鼠的选定大脑区域（皮层、海马、纹状体和小脑）的蛋白质组和磷酸化蛋白质组谱的变化。有趣的是，长时间的吗啡戒断被发现尤其与蛋白质磷酸化的改变有关，并且在较小程度上与蛋白质表达的改变有关。基因本体 (GO) 术语分析揭示了与突触可塑性、细胞骨架组织和 GTP 酶活性相关的生物过程的丰富性。更具体地说，在突触小泡（例如 synapsin-1、SV2a、Rab3a）、突触前神经末梢活性区（例如 Bassoon、Piccolo、Rims1）和突触后密度（例如钙粘蛋白 13、连环蛋白、Arhgap35、Shank3、阿格夫7）。其他差异磷酸化蛋白与微管动力学（微管相关蛋白、Tppp、塌陷蛋白反应介导蛋白）和肌动蛋白-血影蛋白网络（例如血影蛋白、内收蛋白、带 4.1 样蛋白 1）相关。总而言之，六个月的吗啡戒断表现为突触蛋白磷酸化的显着改变。调节突触蛋白功能的磷酸化模式的改变可能有助于药物使用和戒断诱导的长期神经适应。
Drug withdrawal is associated with abstinence symptoms including deficits in cognitive functions that may persist even after prolonged discontinuation of drug intake. Cognitive deficits are, at least partially, caused by alterations in synaptic plasticity but the precise molecular mechanisms have not yet been fully identified. In the present study, changes in proteomic and phosphoproteomic profiles of selected brain regions (cortex, hippocampus, striatum, and cerebellum) from rats abstaining for six months after cessation of chronic treatment with morphine were determined by label-free quantitative (LFQ) proteomic analysis. Interestingly, prolonged morphine withdrawal was found to be associated especially with alterations in protein phosphorylation and to a lesser extent in protein expression. Gene ontology (GO) term analysis revealed enrichment in biological processes related to synaptic plasticity, cytoskeleton organization, and GTPase activity. More specifically, significant changes were observed in proteins localized in synaptic vesicles (e.g., synapsin-1, SV2a, Rab3a), in the active zone of the presynaptic nerve terminal (e.g., Bassoon, Piccolo, Rims1), and in the postsynaptic density (e.g., cadherin 13, catenins, Arhgap35, Shank3, Arhgef7). Other differentially phosphorylated proteins were associated with microtubule dynamics (microtubule-associated proteins, Tppp, collapsin response mediator proteins) and the actin–spectrin network (e.g., spectrins, adducins, band 4.1-like protein 1). Taken together, a six-month morphine withdrawal was manifested by significant alterations in the phosphorylation of synaptic proteins. The altered phosphorylation patterns modulating the function of synaptic proteins may contribute to long-term neuroadaptations induced by drug use and withdrawal.
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影响因子：
3.6
作者：
Areal, Lorena Bianchine;Hamilton, Alison;Ferguson, Stephen S. G.
通讯作者：
Ferguson, Stephen S. G.
影响因子：
3.7
作者：
Duka V;Lee JH;Credle J;Wills J;Oaks A;Smolinsky C;Shah K;Mash DC;Masliah E;Sidhu A
通讯作者：
Sidhu A
影响因子：
4.8
作者：
Collins, MO;Yu, L;Grant, SGN
通讯作者：
Grant, SGN
影响因子：
4.6
作者：
Fernandez-Valenzuela, Juan Jose;Sanchez-Varo, Raquel;Gutierrez, Antonia
通讯作者：
Gutierrez, Antonia
影响因子：
6.1
作者：
CHEN, JC;SMITH, ER;FISHMAN, JB
通讯作者：
FISHMAN, JB