The Effect of Sleep Deprivation and Subsequent Recovery Period on the Synaptic Proteome of Rat Cerebral Cortex.

The Effect of Sleep Deprivation and Subsequent Recovery Period on the Synaptic Proteome of Rat Cerebral Cortex.
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DOI:
10.1007/s12035-021-02699-x
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发表时间:
2022-03
影响因子:
5.1
通讯作者:
Kékesi KA
Kékesi KA
中科院分区:
医学2区
文献类型:
--
作者:
Gulyássy P;Todorov-Völgyi K;Tóth V;Györffy BA;Puska G;Simor A;Juhász G;Drahos L;Kékesi KA

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睡眠剥夺(SD)在现代生活方式中司空见惯,并造成巨大的社会、医疗和人类成本。 睡眠不足会导致认知障碍,例如注意力不集中、工作记忆力下降、情绪调节能力差、反应时间增加,而较高的认知功能特别容易受到睡眠不足的影响。此外,SD 与肥胖、糖尿病、心血管疾病、癌症有关,并且绝大多数精神疾病和神经退行性疾病都伴有睡眠障碍。尽管科学界对睡眠不足对突触功能的影响产生了广泛的兴趣,但缺乏针对蛋白质组水平上的突触传递的研究。在本研究中,我们报告了 SD 和恢复期 (RP) 对大鼠皮质突触蛋白质组的影响。通过温和处理进行 8 小时的 SD 后和 RP 16 小时后分离突触体。通过蛋白质印迹和电子显微镜验证突触体部分的纯度,并通过质谱分析蛋白质丰度变化。我们观察到 SD 和 RP 对突触前膜和突触后膜的神经递质相关蛋白有广泛的影响。 SD 期间突触蛋白丰度的变化程度比 RP 期间更大:我们鉴定出 78 个蛋白在 SD 后丰度发生变化,39 个蛋白在 RP 过程后丰度发生变化。大多数改变的蛋白水平在SD期间上调,而RP则表现出相反的趋势,并且三种蛋白(Gabbr1、Anks1b和Decr1)在SD和RP之后表现出相反方向的丰度变化。功能聚类分析表明,大多数改变的蛋白质与信号转导和调节、突触传递和突触组装、蛋白质和离子运输以及脂质和脂肪酸代谢有关,而相互作用网络分析则揭示了显着改变的蛋白质与突触可塑性或睡眠的分子过程之间的一些联系。我们的蛋白质组数据表明,睡眠剥夺后 SNARE 介导的突触小泡胞吐作用受到抑制,内吞过程受损。 SD 和 RP 都会改变 GABA 神经传递并影响蛋白质合成、多种调节过程和信号传导途径、能量稳态过程和代谢途径。在线版本包含可在 10.1007/s12035-021-02699-x 获取的补充材料。
Sleep deprivation (SD) is commonplace in the modern way of life and has a substantial social, medical, and human cost. Sleep deprivation induces cognitive impairment such as loss of executive attention, working memory decline, poor emotion regulation, increased reaction times, and higher cognitive functions are particularly vulnerable to sleep loss. Furthermore, SD is associated with obesity, diabetes, cardiovascular diseases, cancer, and a vast majority of psychiatric and neurodegenerative disorders are accompanied by sleep disturbances. Despite the widespread scientific interest in the effect of sleep loss on synaptic function, there is a lack of investigation focusing on synaptic transmission on the proteome level. In the present study, we report the effects of SD and recovery period (RP) on the cortical synaptic proteome in rats. Synaptosomes were isolated after 8 h of SD performed by gentle handling and after 16 h of RP. The purity of synaptosome fraction was validated with western blot and electron microscopy, and the protein abundance alterations were analyzed by mass spectrometry. We observed that SD and RP have a wide impact on neurotransmitter-related proteins at both the presynaptic and postsynaptic membranes. The abundance of synaptic proteins has changed to a greater extent in consequence of SD than during RP: we identified 78 proteins with altered abundance after SD and 39 proteins after the course of RP. Levels of most of the altered proteins were upregulated during SD, while RP showed the opposite tendency, and three proteins (Gabbr1, Anks1b, and Decr1) showed abundance changes with opposite direction after SD and RP. The functional cluster analysis revealed that a majority of the altered proteins is related to signal transduction and regulation, synaptic transmission and synaptic assembly, protein and ion transport, and lipid and fatty acid metabolism, while the interaction network analysis revealed several connections between the significantly altered proteins and the molecular processes of synaptic plasticity or sleep. Our proteomic data implies suppression of SNARE-mediated synaptic vesicle exocytosis and impaired endocytic processes after sleep deprivation. Both SD and RP altered GABA neurotransmission and affected protein synthesis, several regulatory processes and signaling pathways, energy homeostatic processes, and metabolic pathways. The online version contains supplementary material available at 10.1007/s12035-021-02699-x.
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发表时间: 2005-12-01
影响因子: 3.9
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