热量限制改善早期社会隔离诱导的小鼠认知功能障碍

牛磊 罗诗诗 曾佳玉 王贞 徐杨 陈熙 曹文宇* 万炜*

doi:10.16098/j.issn.0529-1356.2019.04.003

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解剖学报 ›› 2019, Vol. 50 ›› Issue (4) : 418-422. DOI: 10.16098/j.issn.0529-1356.2019.04.003

神经生物学

热量限制改善早期社会隔离诱导的小鼠认知功能障碍

牛磊¹ 罗诗诗¹ 曾佳玉¹王贞¹徐杨²陈熙¹曹文宇^1* 万炜^1*

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Effect and mechanism of caloric restriction on early social isolation-induced cognitive impairment in mice

NIU Lei¹ LUO Shi-shi¹ ZENG Jia-yu¹ WANG Zhen¹ XU Yang² CHEN Xi¹ CAO Wen-yu^1* WAN Wei^1*

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文章历史 +

摘要

目的探讨热量限制（CR）对早期社会隔离（SI）诱导的认知功能障碍的改善作用及其可能机制。方法 3周龄昆明雄小鼠36只随机分成正常群居组（GH, n=12）、早期社会隔离组（SI, n=12）、热量限制干预组（SI+CR, n=12）。在相同条件下饲养GH组（6只/笼）和SI组（1只/笼），而 SI + CR 组（1只/笼）每隔1 d给予食物。采用旷场实验检测小鼠的活动度，新旧事物识别实验检测小鼠认知功能；免疫组织化学方法检测小鼠海马区小胶质细胞标记物离子钙结合接头分子1（IBA-1）的表达；Western blotting方法检测海马组织小胶质细胞激活标记物CD68及炎症因子白细胞介素-1β（IL-1β）的表达。结果在旷场实验中，3组小鼠的活动度无差异。在新旧事物识别实验中，与GH组相比，SI组新事物分辨率明显下降（P<0.01），海马中IL-1β的表达显著上调（P<0.01），此外，SI组在海马中表现出过度活化的小胶质细胞，表现为IBA-1阳性细胞数量增加，CD68高表达（P<0.01）；与SI组相比，SI+CR组新事物分辨率显著增加（P<0.01），海马IL-1β的表达下调（P<0.01），IBA-1阳性细胞的数量和CD68的表达显著减少（P<0.01）。结论热量限制可缓解早期社会隔离诱导小鼠的认知功能损伤，其机制可能与抑制小胶质细胞的激活及炎症因子的释放有关。

Abstract

Objective To investigate the effect and mechanism of caloric restriction (CR) on early social isolation (SI) induced cognitive dysfunction in mice. Methods Thirty-six kunming mice (3-weeks old) were randomly divided into group house (GH, n=12), early socially isolated (SI, n=12), caloric restriction and socially isolated (SI+CR, n=12).The GH group (6 mice/cage) and SI group (1 mice/cage) were reared separately under the same conditions, while the SI+CR group (1 mice/cage) were given food every other day. The open field experiment was used to measure the locomotive of mice; The object recognition task was used to evaluate the cognitive function; The expression of microglial marker ionized calcium-binding adapter molecule 1 (IBA-1) in hippocampus was detected by immunohistochemistry. The expression of microglial activation marker CD68 and interleukin-1β (IL-1β) in hippocampus was detected by Western blotting. Results In the open field test, there was no difference in the activity of the three groups of mice. Compared with the GH group, the SI group showed significantly reduced discrimination ratio in object recognition task, with remarkably up-regulated expression of IL-1β in hippocampus (P<0.01). In addition, SI group exhibited over-activated microglia in hippocampus indicated by increased number of IBA-1-positive cells and high expression of CD68 (P<0.01). Compared with the SI group, SI+CR group enhanced discrimination ratio in object recognition task, with down-regulated expression of IL-1β in hippocampus (P<0.01), and the number of IBA-1-positive cells and the expression of CD68 significantly reduced (P<0.01). Conclusion Caloric restriction alleviates SI-induced cognitive dysfunction, which might be attributed to the inhibiting of microglia activation in the hippocampus.

导出引用

牛磊罗诗诗曾佳玉王贞徐杨陈熙曹文宇万炜. 热量限制改善早期社会隔离诱导的小鼠认知功能障碍[J]. 解剖学报. 2019, 50(4): 418-422 https://doi.org/10.16098/j.issn.0529-1356.2019.04.003

NIU Lei LUO Shi-shi ZENG Jia-yu WANG Zhen XU Yang CHEN Xi CAO Wen-yu WAN Wei. Effect and mechanism of caloric restriction on early social isolation-induced cognitive impairment in mice[J]. Acta Anatomica Sinica. 2019, 50(4): 418-422 https://doi.org/10.16098/j.issn.0529-1356.2019.04.003

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基金

湖南省自然科学基金青年基金项目;湖南省自然科学基金青年基金项目;湖南省自然科学基金青年基金项目;湖南省自然科学基金省市联合基金项目;湖南省教育厅重点项目;湖南省教育厅重点项目;湖南省教育厅优秀青年项目;南华大学博士科研启动基金;南华大学博士科研启动基金;南华大学大学生研究性学习和创新项目;南华大学大学生研究性学习和创新项目;南华大学大学生研究性学习和创新项目;湖南省卫生计生委科研课题计划项目