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伯氏疟原虫 ANKA 无并发症感染对 C57BL/6 小鼠记忆和焦虑样行为的长期影响。

Long-term effect of uncomplicated Plasmodium berghei ANKA malaria on memory and anxiety-like behaviour in C57BL/6 mice.

机构信息

Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz & Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal) da Fundação Oswaldo Cruz (Fiocruz) e da Secretaria de Vigilância em Saúde (SVS), Ministério da Saúde, Rio de Janeiro, Brazil.

Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

出版信息

Parasit Vectors. 2018 Mar 20;11(1):191. doi: 10.1186/s13071-018-2778-8.

Abstract

BACKGROUND

Cerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported in chronically exposed residents of endemic areas, but not in some murine experimental models of non-cerebral malaria. This study aimed at evaluating the influence of uncomplicated malaria on different behavioural paradigms associated with memory and anxiety-like parameters in a murine model that has the ability to develop cerebral malaria.

METHODS

Plasmodium berghei ANKA-infected and non-infected C57BL/6 mice were used. Development of cerebral malaria was prevented by chloroquine treatment starting on the fourth day of infection. The control group (non-infected mice) were treated with PBS. The effect of uncomplicated malaria infection on locomotor habituation, short and long-term memory and anxious-like behaviour was evaluated 64 days after parasite clearance in assays including open field, object recognition, Y-maze and light/dark tasks.

RESULTS

Plasmodium berghei ANKA-infected mice showed significant long-lasting disturbances reflected by a long-term memory-related behaviour on open field and object recognition tasks, accompanied by an anxious-like phenotype availed on open field and light-dark tasks.

CONCLUSIONS

Long-term neurocognitive sequels may follow an uncomplicated malaria episode in an experimental model prone to develop cerebral malaria, even if the infection is treated before the appearance of clinical signs of cerebral impairment.

摘要

背景

脑型疟疾是人类感染恶性疟原虫的主要并发症,与人类疾病和实验性疟原虫感染的小鼠模型中的持续神经认知后遗症有关。近年来,在流行地区的慢性暴露居民中也报道了与无并发症(非脑型)疟疾相关的认知缺陷,但在某些非脑型疟疾的实验性小鼠模型中并未报道。本研究旨在评估无并发症疟疾对记忆和焦虑样参数相关的不同行为范式的影响,这在一种有能力发展为脑型疟疾的实验性小鼠模型中进行。

方法

使用感染了伯氏疟原虫 ANKA 和未感染的 C57BL/6 小鼠。从感染的第四天开始用氯喹治疗来预防脑型疟疾的发展。对照组(未感染的小鼠)用 PBS 处理。在寄生虫清除后 64 天,通过旷场、物体识别、Y 迷宫和明暗任务等检测,评估无并发症疟疾感染对运动习惯化、短期和长期记忆以及焦虑样行为的影响。

结果

感染了伯氏疟原虫 ANKA 的小鼠在旷场和物体识别任务中表现出明显的长期持久干扰,反映出长期记忆相关行为受损,同时在旷场和明暗任务中表现出焦虑样表型。

结论

即使在出现脑损伤的临床症状之前进行治疗,无并发症疟疾感染后可能会在易发生脑型疟疾的实验性模型中引起长期神经认知后遗症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/989c/5859440/06fb4cff8de0/13071_2018_2778_Fig1_HTML.jpg

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