Brain Interleukin-1 Facilitates Learning of a Water Maze Spatial Memory Task in Young Mice.

Brain Interleukin-1 Facilitates Learning of a Water Maze Spatial Memory Task in Young Mice.
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DOI:
10.3389/fnbeh.2017.00202
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发表时间:
2017
影响因子:
3
通讯作者:
Kawakami M
Kawakami M
中科院分区:
医学3区
文献类型:
--
作者:
Takemiya T;Fumizawa K;Yamagata K;Iwakura Y;Kawakami M

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促炎细胞因子白细胞介素-1(IL-1)由许多类型的细胞产生,包括外周中的免疫细胞和脑中的神经胶质和神经元。I型IL-1受体(IL-1 r1)主要负责传递IL-1的炎症效应,并通过与IL-1α或IL-1β结合介导多种生物学功能。IL-1β激活与海马依赖性记忆任务相关。虽然IL-1β在某些病理生理条件下损害空间记忆,但IL-1β可能是海马可塑性和记忆的正常生理调节所必需的。此外,脑IL-1β水平被认为以年龄依赖性方式在海马中变化。这些发现表明,IL-1β可能对年轻小鼠的学习和记忆具有有益的暂时影响,但这一问题仍不清楚。因此,我们假设海马IL-1β通过IL-1 r1对年轻小鼠的空间学习和记忆具有有益作用,而IL-1 r1在成年小鼠中减少。我们调查了年轻人的表现,(3个月)和成人(6月龄)野生型小鼠,IL-1β敲除小鼠(IL-1βko)和IL-1 r1敲除小鼠本研究旨在观察IL-1β(IL-1 r1 ko)在水迷宫(WM)中学习空间记忆任务中的作用,并采用均相时间分辨荧光(HTRF)。在WM空间记忆任务的训练试验中,幼年IL-1βko和IL-1 r1 ko小鼠的学习能力显著受损,但成年IL-1βko和IL-1 r1 ko小鼠的学习能力未受损。此外,IL-1βko小鼠的长期记忆消退没有受到影响,而IL-1 r1 ko小鼠的长期记忆消退受到损害,这表明IL-1α可能促进记忆消退。在这项研究中,使用HTRF的细胞因子测定未表明幼龄小鼠海马IL-1的表达较高,但成年小鼠皮质IL-1β和IL-1α显著升高。我们需要进一步研究皮质IL-1的作用以及海马神经元局部IL-1的表达。
The proinflammatory cytokine interleukin-1 (IL-1) is produced by many types of cells, including immune cells in the periphery and glia and neurons in the brain. The type I IL-1 receptor (IL-1r1) is primarily responsible for transmitting the inflammatory effects of IL-1 and mediates several biological functions by binding to either IL-1α or IL-1β. IL-1β activation is associated with hippocampus-dependent memory tasks. Although IL-1β impairs spatial memory under certain pathophysiological conditions, IL-1β may be required for the normal physiological regulation of hippocampal plasticity and memory. In addition, brain IL-1β levels are thought to change in the hippocampus in an age-dependent manner. These findings suggest that IL-1β may have a beneficial, temporary effect on learning and memory in young mice, but the matter remains unclear. Therefore, we hypothesized that hippocampal IL-1β has a beneficial effect on spatial learning and memory in young mice via IL-1r1, which is diminished in adults. We investigated the performance of young (3-month-old) and adult (6-month-old) wild-type mice, IL-1β knockout mice (IL-1βko) and IL-1r1 knockout mice (IL-1r1ko) in learning a spatial memory task with a fixed platform in a water maze (WM) and measured the levels of IL-1β and IL-1α in the hippocampus and cortex of adult and young mice by using homogeneous time-resolved fluorescence (HTRF). Learning was significantly impaired in the training trials of the WM spatial memory task in young IL-1βko and IL-1r1ko mice but not in adult IL-1βko and IL-1r1ko mice. Moreover, young IL-1r1ko mice but not IL-1βko mice showed an impairment in long-term memory extinction, suggesting that IL-1α might facilitate memory extinction. In this study, the cytokine assay using HTRF did not indicate a higher expression of hippocampal IL-1 in young mice but cortical IL-1β and IL-1α were significantly increased in adult mice. We need to investigate the role of cortical IL-1 and the local IL-1 expression in the hippocampal neurons in the future.
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