Proteomic analysis of cortical brain tissue from the BTBR mouse model of autism: Evidence for changes in STOP and myelin-related proteins
Proteomic analysis of cortical brain tissue from the BTBR mouse model of autism: Evidence for changes in STOP and myelin-related proteins
复制标题
DOI：
10.1016/j.neuroscience.2015.11.003
复制
发表时间：
2016-01
期刊：
影响因子：
3.3
通讯作者：
H. Wei;Y. Ma;J. Liu;C. Ding;F. Hu;L. Yu
中科院分区：
文献类型：
--
作者：
H. Wei;Y. Ma;J. Liu;C. Ding;F. Hu;L. Yu
孤独症是一种神经发育障碍，其特征是异常的相互社会互动，沟通障碍和重复性行为与有限的利益。然而，广泛接受的自闭症生物标志物仍然缺乏。在这项研究中，我们进行了定量蛋白质组分析研究的皮质脑组织从BTBRT + Itpr3tf（BTBR）小鼠，小鼠模型，显示自闭症样表型。使用同量异位素标签相对和绝对定量（iTRAQ）结合LC-MS/MS，在小鼠皮质中总共定量了3611种蛋白质。与C57BL/6J（B6）小鼠相比，BTBR小鼠脑组织中有126个差异表达蛋白。对差异表达蛋白进行功能注释和分类。Western blotting结果显示，BTBR小鼠的稳定微管多肽（stable tubule only polypeptide，STOP）和髓鞘相关蛋白表达明显下调。此外，与B6对照相比，BTBR小鼠显示铁明矾染色水平降低，表明髓鞘破坏。最后，我们提出，在大脑中的STOP表达减少可能参与介导的自闭症样行为，通过在少突胶质细胞和神经元的突触功能髓鞘的损伤。STOP蛋白的操纵可能是自闭症治疗干预的一个有前途的途径。
Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. However, the widely accepted biomarkers for autism are still lacking. In this study, we carried out a quantitative proteomic profiling study of cortical brain tissue from BTBRT+Itpr3tf(BTBR) mice, a mouse model that displays an autism-like phenotype. Using isobaric tag for relative and absolute quantification (iTRAQ) coupled with LC–MS/MS, a total of 3611 proteins were quantitated in mouse cortices. As compared to C57BL/6J (B6) mice, 126 differentially expressed proteins were found in the brain from BTBR mice. The functional annotation and categories of differentially expressed proteins were analyzed. Especially, the stable tubule only polypeptide (STOP) protein and myelin-related proteins down-regulated significantly in BTBR mice were confirmed by Western blotting. Furthermore, the BTBR mice displayed reduced levels of staining with ferric alum in comparison to B6 controls, indicative of myelin disruption. Finally, we propose that reduced STOP expression in the brain could be involved in the mediation of autism-like behaviors through impairments of myelination in oligodendrocytes and synaptic function in neurons. Manipulation of STOP protein could be a promising avenue for therapeutic interventions to autism.