Proteomic analysis of post mortem brain tissue from autism patients: evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity-related proteins.
Proteomic analysis of post mortem brain tissue from autism patients: evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity-related proteins.
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DOI：
10.1186/2040-2392-5-41
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发表时间：
2014
期刊：
影响因子：
6.2
通讯作者：
Bahn S
中科院分区：
文献类型：
--
作者：
Broek JA;Guest PC;Rahmoune H;Bahn S
自闭症是一种神经发育障碍，其特征是语言、沟通和社交技能受损。尽管在这一领域已经进行了遗传学研究，但没有一个已识别的基因能够解释其根本原因。在这里，我们通过对自闭症患者和对照的死后大脑样本进行蛋白质组学分析来研究分子改变。该分析主要集中在前额皮质和小脑，因为之前的研究发现这两个大脑区域在结构和功能上是相连的，并且它们与自闭症有关。使用选择反应监测质谱（SRM-MS）对自闭症患者和匹配对照的死后前额皮质和小脑样本进行分析。主要目标是识别显着改变的蛋白质和生物途径，并在这两个大脑区域进行比较。靶向 SRM-MS 鉴定出与髓鞘形成、突触小泡调节和能量代谢相关的蛋白质水平发生变化。这表明两个大脑区域中未成熟星形胶质细胞标记波形蛋白的水平下降，表明星形胶质细胞前体细胞减少。此外，在前额皮质中发现与髓鞘形成相关的蛋白质水平降低，突触和能量相关蛋白质增加，表明突触连接性增加。最后，发现小脑中髓鞘形成和突触蛋白发生相反方向的变化。这些发现表明，自闭症患者的前额叶皮层和小脑的结构和/或功能连接发生了改变，对涉及髓鞘形成和突触功能的蛋白质产生相反的影响就表明了这一点。对这些发现的进一步研究可能有助于增加我们对自闭症与大脑连接相关的机制的理解，最终目的是促进新的治疗方法。
Autism is a neurodevelopmental disorder characterized by impaired language, communication and social skills. Although genetic studies have been carried out in this field, none of the genes identified have led to an explanation of the underlying causes. Here, we have investigated molecular alterations by proteomic profiling of post mortem brain samples from autism patients and controls. The analysis focussed on prefrontal cortex and cerebellum as previous studies have found that these two brain regions are structurally and functionally connected, and they have been implicated in autism. Post mortem prefrontal cortex and cerebellum samples from autism patients and matched controls were analysed using selected reaction monitoring mass spectrometry (SRM-MS). The main objective was to identify significantly altered proteins and biological pathways and to compare these across these two brain regions. Targeted SRM-MS resulted in identification of altered levels of proteins related to myelination, synaptic vesicle regulation and energy metabolism. This showed decreased levels of the immature astrocyte marker vimentin in both brain regions, suggesting a decrease in astrocyte precursor cells. Also, decreased levels of proteins associated with myelination and increased synaptic and energy-related proteins were found in the prefrontal cortex, indicative of increased synaptic connectivity. Finally, opposite directional changes were found for myelination and synaptic proteins in the cerebellum. These findings suggest altered structural and/or functional connectivity in the prefrontal cortex and cerebellum in autism patients, as shown by opposite effects on proteins involved in myelination and synaptic function. Further investigation of these findings could help to increase our understanding of the mechanisms underlying autism relating to brain connectivity, with the ultimate aim of facilitating novel therapeutic approaches.
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影响因子：
1.9
作者：
Mostafa, Gehan Ahmed;El-Sayed, Zeinab Awad;Ei-Saned, Mohamed Farouk
通讯作者：
Ei-Saned, Mohamed Farouk
影响因子：
2.5
作者：
LEICHNETZ, GR;SMITH, DJ;SPENCER, RF
通讯作者：
SPENCER, RF
影响因子：
14.9
作者：
Basu SN;Kollu R;Banerjee-Basu S
通讯作者：
Banerjee-Basu S
影响因子：
3.5
作者：
Fatemi, S. Hossein;Aldinger, Kimberly A.;Ashwood, Paul;Bauman, Margaret L.;Blaha, Charles D.;Blatt, Gene J.;Chauhan, Abha;Chauhan, Ved;Dager, Stephen R.;Dickson, Price E.;Estes, Annette M.;Goldowitz, Dan;Heck, Detlef H.;Kemper, Thomas L.;King, Bryan H.;Martin, Loren A.;Millen, Kathleen J.;Mittleman, Guy;Mosconi, Matthew W.;Persico, Antonio M.;Sweeney, John A.;Webb, Sara J.;Welsh, John P.
通讯作者：
Welsh, John P.
DOI：
10.1023/b:jadd.0000005998.47370.ef
发表时间：
2003-12-01
影响因子：
3.9
作者：
Goldberg, WA;Osann, K;Spence, MA
通讯作者：
Spence, MA