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趋化因子受体信号传导对CCR6和CCR7基因敲除小鼠认知样、情绪样和社交行为的影响。

Effects of chemokine receptor signalling on cognition-like, emotion-like and sociability behaviours of CCR6 and CCR7 knockout mice.

作者信息

Jaehne E J, Baune B T

机构信息

Discipline of Psychiatry, University of Adelaide, Adelaide, Australia.

Discipline of Psychiatry, University of Adelaide, Adelaide, Australia.

出版信息

Behav Brain Res. 2014 Mar 15;261:31-9. doi: 10.1016/j.bbr.2013.12.006. Epub 2013 Dec 12.

Abstract

Inflammation is regarded as an important mechanism of neuropsychiatric disorders. Chemokines, which are a part of the immune system, have effects on various aspects of brain function, but little is known about their effects on behaviour. We have compared the cognition-like behaviour (learning and spatial memory) of CCR6(-/-) and CCR7(-/-) mice with wild type (WT) C57BL/6 mice, in the Barnes maze, as well as a range of other behaviours, including exploratory, anxiety and depression-like behaviour, using a battery of tests. Levels of cytokines TNF-α, IL-1β and IL-6 were also measured. In the Barnes maze, CCR7(-/-) mice were shown to take longer to learn the location of the escape box on the 1st of 4 days of training. In the behavioural battery, CCR6(-/-) mice showed higher locomotor activity and lower anxiety in the open field test, and a lack of preference for social novelty in a sociability test. CCR7(-/-) mice behaved much like WT mice, although showed higher anxiety in Elevated Zero Maze. While baseline saccharin preference in a 2-bottle choice test, a test for anhedonia depression-like behaviour, was equal in all strains at baseline, weekly tests showed that both CCR6(-/-) and CCR7(-/-) mice developed a decreased preference for saccharin compared to WT over time. There were no differences between strains in any of the cytokines measured. These results suggest that chemokine receptors may play a role in cognition and learning behaviour, as well as anxiety and other behaviours, although the biological mechanisms are still unclear.

摘要

炎症被认为是神经精神疾病的重要机制。趋化因子作为免疫系统的一部分,对脑功能的各个方面都有影响,但人们对其对行为的影响知之甚少。我们使用一系列测试,比较了CCR6(-/-)和CCR7(-/-)小鼠与野生型(WT)C57BL/6小鼠在巴恩斯迷宫中的认知样行为(学习和空间记忆),以及一系列其他行为,包括探索性、焦虑和抑郁样行为。还测量了细胞因子TNF-α、IL-1β和IL-6的水平。在巴恩斯迷宫中,CCR7(-/-)小鼠在训练的第4天的第1天学习逃生箱位置的时间更长。在行为测试中,CCR6(-/-)小鼠在旷场试验中表现出更高的运动活性和更低的焦虑,并且在社交性测试中对社交新奇性缺乏偏好。CCR7(-/-)小鼠的行为与WT小鼠非常相似,尽管在高架零迷宫中表现出更高的焦虑。虽然在双瓶选择试验(一种用于检测快感缺失抑郁样行为的试验)中,所有品系在基线时的糖精偏好相同,但每周测试表明,随着时间的推移,CCR6(-/-)和CCR7(-/-)小鼠与WT小鼠相比,对糖精的偏好都有所下降。在所测量的任何细胞因子中,各品系之间没有差异。这些结果表明,趋化因子受体可能在认知和学习行为以及焦虑和其他行为中发挥作用,尽管其生物学机制仍不清楚。

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