Toxoplasma gondii induces metabolic disturbances in the hippocampus of BALB/c mice
Toxoplasma gondii induces metabolic disturbances in the hippocampus of BALB/c mice
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弓形虫引起 BALB/c 小鼠海马代谢紊乱
DOI：
10.1007/s00436-021-07222-8
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发表时间：
2021-07
影响因子：
2
通讯作者：
Zhu Xing-Quan
中科院分区：
文献类型：
--
作者：
Ma Jun;He Jun-Jun;Wang Meng;Hou Jun-Ling;Elsheikha Hany M.;Zhu Xing-Quan
弓形虫可以穿过血脑屏障，感染大脑的不同区域，包括海马体。在本研究中，我们利用超高效液相色谱-串联质谱仪检测了弓形虫感染对雌性BALB/c小鼠海马区代谢的影响，并与对照组小鼠进行了比较。多变量分析显示，感染后7、14和21天，感染组和对照组之间差异显著，分别鉴定出25、82和105个差异代谢物(DM)。在弓形虫感染后的各个时间点，均检测到1条神经鞘氨醇-磷脂酰胆碱途径(DM)和11条异常调节途径，提示它们在弓形虫感染的神经发病机制中起重要作用。这些通路与神经活动有关，如炎症介质对色氨酸通道的调节、逆行内源性大麻素信号和花生四烯酸代谢。加权相关网络分析和接收器工作特性分析确定了33个与弓形虫感染显著相关的代谢物，其中30个被认为是弓形虫感染的潜在生物标志物。这项研究首次提供了弓形虫感染期间小鼠海马区代谢扰动的全球视角。已识别的代谢物和途径的潜在相关性与认知障碍和精神障碍的发病机制进行了讨论。
Toxoplasma gondii can cross the blood-brain barrier and infect different regions of the brain including the hippocampus. In the present study, we examined the impact of Toxoplasma gondii infection on the metabolism of the hippocampus of female BALB/c mice compared to control mice using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariate analysis revealed significant differences between infected and control hippocampi and identified 25, 82, and 105 differential metabolites (DMs) in the infected hippocampi at 7, 14, and 21 days post-infection (dpi), respectively. One DM (sphingosyl-phosphocholine in the sphingolipid metabolism pathway) and 11 dysregulated pathways were detected at all time points post-infection, suggesting their important roles in the neuropathogenesis of T. gondii infection. These pathways were related to neural activity, such as inflammatory mediator regulation of TRP channels, retrograde endocannabinoid signaling, and arachidonic acid metabolism. Weighted correlation network analysis and receiver operating characteristic analysis identified 33 metabolites significantly associated with T. gondii infection in the hippocampus, and 30 of these were deemed as potential biomarkers for T. gondii infection. This study provides, for the first time, a global view of the metabolic perturbations that occur in the mouse hippocampus during T. gondii infection. The potential relevance of the identified metabolites and pathways to the pathogenesis of cognitive impairment and psychiatric disorders are discussed.
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影响因子：
8
作者：
Mencarelli, Chiara;Martinez-Martinez, Pilar
通讯作者：
Martinez-Martinez, Pilar
DOI：
10.1523/jneurosci.3039-08.2008
发表时间：
2008-10-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bedny M;Caramazza A;Grossman E;Pascual-Leone A;Saxe R
通讯作者：
Saxe R
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：
2.7
作者：
E. Sugiyama;K. Uemura;A. Hara;T. Taketomi
通讯作者：
E. Sugiyama;K. Uemura;A. Hara;T. Taketomi
影响因子：
9.3
作者：
Torres L;Robinson SA;Kim DG;Yan A;Cleland TA;Bynoe MS
通讯作者：
Bynoe MS