Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition.
Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition.
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DOI：
10.1186/s12974-018-1242-1
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发表时间：
2018-08-01
影响因子：
9.3
通讯作者：
Dunay IR
中科院分区：
文献类型：
--
作者：
Lang D;Schott BH;van Ham M;Morton L;Kulikovskaja L;Herrera-Molina R;Pielot R;Klawonn F;Montag D;Jänsch L;Gundelfinger ED;Smalla KH;Dunay IR
嗜神经性寄生虫弓形虫的慢性感染与几种神经精神疾病的风险有关。寄生虫可以改变宿主的神经功能和行为的机制尚不完全清楚。在这里，一种新的蛋白质组学方法使用质谱学方法来研究慢性弓形虫病小鼠模型突触蛋白成分的变化。在基于候选的策略中，免疫印迹分析和免疫组织化学被用来研究谷氨酸能信号中关键突触蛋白的表达水平。对突触体蛋白组成的比较显示，感染后突触体蛋白发生明显变化，EAAT2、Shank3、AMPA受体和NMDA受体亚基等多种蛋白下调，而炎症相关蛋白上调。抗寄生虫药磺胺嘧啶的治疗显著降低了速殖子水平，减少了神经炎性介质。然而，在这两种情况下，大量的潜伏囊肿持续存在于大脑中。相反，与感染相关的关键突触蛋白水平的变化可能会被药物治疗部分逆转。这些结果为弓形虫感染小鼠的突触蛋白组成发生了深刻的变化提供了证据，这些变化下调了谷氨酸能神经传递的关键成分。我们的结果表明，检测到的突触改变是由嗜神经性寄生虫引起的独特的神经炎性环境的结果。本文的在线版本(10.1186/s12974-0181242-1)包含补充材料，可供授权用户使用。
Chronic infection with the neurotropic parasite Toxoplasma gondii has been implicated in the risk for several neuropsychiatric disorders. The mechanisms, by which the parasite may alter neural function and behavior of the host, are not yet understood completely. Here, a novel proteomic approach using mass spectrometry was employed to investigate the alterations in synaptic protein composition in a murine model of chronic toxoplasmosis. In a candidate-based strategy, immunoblot analysis and immunohistochemistry were applied to investigate the expression levels of key synaptic proteins in glutamatergic signaling. A comparison of the synaptosomal protein composition revealed distinct changes upon infection, with multiple proteins such as EAAT2, Shank3, AMPA receptor, and NMDA receptor subunits being downregulated, whereas inflammation-related proteins showed an upregulation. Treatment with the antiparasitic agent sulfadiazine strongly reduced tachyzoite levels and diminished neuroinflammatory mediators. However, in both conditions, a significant number of latent cysts persisted in the brain. Conversely, infection-related alterations of key synaptic protein levels could be partly reversed by the treatment. These results provide evidence for profound changes especially in synaptic protein composition in T. gondii-infected mice with a downregulation of pivotal components of glutamatergic neurotransmission. Our results suggest that the detected synaptic alterations are a consequence of the distinct neuroinflammatory milieu caused by the neurotropic parasite. The online version of this article (10.1186/s12974-018-1242-1) contains supplementary material, which is available to authorized users.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
6.7
作者：
David CN;Frias ES;Szu JI;Vieira PA;Hubbard JA;Lovelace J;Michael M;Worth D;McGovern KE;Ethell IM;Stanley BG;Korzus E;Fiacco TA;Binder DK;Wilson EH
通讯作者：
Wilson EH
影响因子：
5.7
作者：
Czarnewski P;Araújo ECB;Oliveira MC;Mineo TWP;Silva NM
通讯作者：
Silva NM
影响因子：
5.7
作者：
Biswas A;French T;Düsedau HP;Mueller N;Riek-Burchardt M;Dudeck A;Bank U;Schüler T;Dunay IR
通讯作者：
Dunay IR
影响因子：
3.7
作者：
Flegr, J;Havlicek, J;Smahel, Z
通讯作者：
Smahel, Z