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慢性弓形虫感染与小鼠的睡眠-觉醒改变。

Chronic Toxoplasma gondii infection and sleep-wake alterations in mice.

机构信息

Institut des Agents Infectieux, Parasitologie Mycologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.

Physiologie intégrée du système d'éveil, Faculté de Médecine, Centre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR 5292, Université Claude Bernard Lyon 1, Lyon, France.

出版信息

CNS Neurosci Ther. 2021 Aug;27(8):895-907. doi: 10.1111/cns.13650. Epub 2021 Jun 4.

Abstract

AIM

Toxoplasma gondii (Tg) is an intracellular parasite infecting more than a third of the human population. Yet, the impact of Tg infection on sleep, a highly sensitive index of brain functions, remains unknown. We designed an experimental mouse model of chronic Tg infection to assess the effects on sleep-wake states.

METHODS

Mice were infected using cysts of the type II Prugniaud strain. We performed chronic sleep-wake recordings and monitoring as well as EEG power spectral density analysis in order to assess the quantitative and qualitative changes of sleep-wake states. Pharmacological approach was combined to evaluate the direct impact of the infection and inflammation caused by Tg.

RESULTS

Infected mouse exhibited chronic sleep-wake alterations over months, characterized by a marked increase (>20%) in time spent awake and in cortical EEG θ power density of all sleep-wake states. Meanwhile, slow-wave sleep decreased significantly. These effects were alleviated by an anti-inflammatory treatment using corticosteroid dexamethasone.

CONCLUSION

We demonstrated for the first time the direct consequences of Tg infection on sleep-wake states. The persistently increased wakefulness and reduced sleep fit with the parasite's strategy to enhance dissemination through host predation and are of significance in understanding the neurodegenerative and neuropsychiatric disorders reported in infected patients.

摘要

目的

刚地弓形虫(Tg)是一种感染超过三分之一人口的细胞内寄生虫。然而,Tg 感染对睡眠(大脑功能的一个高度敏感指标)的影响尚不清楚。我们设计了一种慢性 Tg 感染的实验小鼠模型,以评估其对睡眠-觉醒状态的影响。

方法

使用 II 型普鲁格纳尤德(Prugniaud)株的包囊对小鼠进行感染。我们进行了慢性睡眠-觉醒记录和监测以及 EEG 功率谱密度分析,以评估睡眠-觉醒状态的定量和定性变化。结合药理学方法来评估感染和 Tg 引起的炎症对睡眠-觉醒的直接影响。

结果

感染的小鼠在数月内表现出慢性睡眠-觉醒改变,其特征是清醒时间和所有睡眠-觉醒状态的皮质 EEG θ 功率密度显著增加(>20%)。同时,慢波睡眠显著减少。这些影响通过使用皮质类固醇地塞米松进行抗炎治疗得到缓解。

结论

我们首次证明了 Tg 感染对睡眠-觉醒状态的直接影响。持续增加的觉醒和减少的睡眠与寄生虫通过宿主捕食来增强传播的策略相吻合,这对于理解感染患者报告的神经退行性和神经精神障碍具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e56a/8265947/fe13c2fb3a6e/CNS-27-895-g005.jpg

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