Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer's disease in wild-type, C57BL/6 mice.
Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer's disease in wild-type, C57BL/6 mice.
复制标题
DOI：
10.1186/s12974-018-1086-8
复制
发表时间：
2018-02-23
影响因子：
9.3
通讯作者：
Bynoe MS
中科院分区：
文献类型：
--
作者：
Torres L;Robinson SA;Kim DG;Yan A;Cleland TA;Bynoe MS
阿尔茨海默病（AD）是一种进行性神经退行性疾病，与认知能力下降和基本功能完全丧失有关。无处不在的顶复体寄生虫弓形虫（弓形虫）感染了世界上三分之一的人口，并与阿尔茨海默病有关。我们用10个弓形虫ME49囊肿感染C57BL/6野生型雄性和雌性小鼠，并通过免疫组织化学、免疫荧光、Western blotting、细胞培养试验以及一系列小鼠行为测试来评估感染是否导致行为和解剖影响。我们发现弓形虫感染在C57BL/6雄性和雌性小鼠的大脑中诱导了AD的两个主要特征：β -淀粉样蛋白（Aβ）免疫反应性和过度磷酸化的Tau。感染小鼠表现出明显的神经元死亡、n -甲基-d-天冬氨酸受体（NMDAR）表达缺失和嗅觉感觉神经元缺失。弓形虫感染还会导致焦虑样行为、对社会新奇事物的认知改变、空间记忆改变和嗅觉敏感性降低。最后一项发现仅适用于雄性小鼠，因为受感染的雌性小鼠表现出完整的嗅觉敏感性。这些结果表明，弓形虫可以在野生型小鼠中诱发阿尔茨海默病的晚期症状，并可能在一些有潜在健康问题的个体中诱发阿尔茨海默病。本文的在线版本（10.1186/s12974-018-1086-8）包含补充材料，可供授权用户使用。
Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with cognitive decline and complete loss of basic functions. The ubiquitous apicomplexan parasite Toxoplasma gondii (T. gondii) infects up to one third of the world’s population and is implicated in AD. We infected C57BL/6 wild-type male and female mice with 10 T. gondii ME49 cysts and assessed whether infection led to behavioral and anatomical effects using immunohistochemistry, immunofluorescence, Western blotting, cell culture assays, as well as an array of mouse behavior tests. We show that T. gondii infection induced two major hallmarks of AD in the brains of C57BL/6 male and female mice: beta-amyloid (Aβ) immunoreactivity and hyperphosphorylated Tau. Infected mice showed significant neuronal death, loss of N-methyl-d-aspartate receptor (NMDAR) expression, and loss of olfactory sensory neurons. T. gondii infection also caused anxiety-like behavior, altered recognition of social novelty, altered spatial memory, and reduced olfactory sensitivity. This last finding was exclusive to male mice, as infected females showed intact olfactory sensitivity. These results demonstrate that T. gondii can induce advanced signs of AD in wild-type mice and that it may induce AD in some individuals with underlying health problems. The online version of this article (10.1186/s12974-018-1086-8) contains supplementary material, which is available to authorized users.
登录
查看更多内容
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：
2.9
作者：
Filali, Mohammed;Lalonde, Robert;Rivest, Serge
通讯作者：
Rivest, Serge
影响因子：
15.1
作者：
Gajewski, Patrick D.;Falkenstein, Michael;Golka, Klaus
通讯作者：
Golka, Klaus
影响因子：
2.5
作者：
GOEDERT, M;JAKES, R;VANMECHELEN, E
通讯作者：
VANMECHELEN, E
影响因子：
15.1
作者：
Evans, Andrew K.;Strassmann, Patrick S.;Lee, I-Ping;Sapolsky, Robert M.
通讯作者：
Sapolsky, Robert M.