芪复饮通过CCR3信号抑制小胶质细胞衰老,抗ccl11诱导的认知功能障碍。

IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Sheng Tian, Tianyuan Ye, Chao Tian, Yipeng Zhang, He Li, Hui Shen, Youhua Xu, Xiaorui Cheng
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引用次数: 0

摘要

背景:趋化因子CCL11与认知功能呈负相关,可引起突触可塑性功能障碍。本研究探讨CCL11是否诱导小胶质细胞衰老损害突触可塑性及芪复饮的保护作用。方法:采用CCL11腹腔注射C57BL/6小鼠,建立衰老小鼠模型。通过行为测试评价芪附饮治疗后认知功能的变化。LTP染色和高尔基染色评价突触结构和功能。使用SA-β-Gal染色评估细胞衰老,使用多重免疫荧光鉴定p21或p16与Iba-1共定位,并通过Luminex评估衰老相关分泌表型(SASP)。用益腑饮的5种入脑成分处理CCR3敲除/过表达的HMC3细胞,观察益腑饮的保护作用。结果:本研究发现芪附饮可改善ccl11诱导的C57BL/6小鼠的物体识别记忆能力、空间学习记忆能力和条件恐惧记忆能力。芪复饮可改善ccl11诱导小鼠海马突触可塑性,增加海马组织中GAP-43、PSD-95、SYN的表达。芪附饮治疗后,小胶质细胞的衰老程度和海马中SASP的含量均有所降低。通过对CCR3基因敲除/过表达的HMC3细胞的研究发现,芪复饮脑组分可以解除CCL11/CCR3通路诱导的细胞周期阻滞,降低G0和G1细胞比例,降低p16、p21和SASP的表达,增强HMC3细胞损伤的HT-22细胞的突触连接。结论:本研究发现CCL11使脑内小胶质细胞衰老,导致突触结构损伤,神经元功能可塑性受损,从而导致学习记忆功能中断。芪复饮可延缓小胶质细胞衰老,维护突触可塑性,增强认知功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Qifuyin against CCL11-Induced cognitive impairment by inhibiting microglial senescence via CCR3 signaling.

Background: The chemokine CCL11 is negatively correlated with cognitive function and is able to cause dysfunctions of synaptic plasticity. This research investigate whether CCL11 induce microglia senescence to damage synaptic plasticity and the protective role of Qifuyin.

Method: This study involved the intraperitoneal injection of CCL11 in C57BL/6 mice to create an ageing mouse model. Behavioral tests were conducted to evaluate the changes in cognitive function after Qifuyin treatment. LTP and Golgi staining were used to evaluate synaptic structure and function. Cellular senescence was assessed using SA-β-Gal staining, co-localization of p21 or p16 with Iba-1 was identified using multiplex immunofluorescence, and senescence-associated secretory phenotype (SASP) was evaluated via the Luminex. CCR3 knockout/overexpression HMC3 cells were treated with five brain-entering components of Qifuyin to observe protective effects of Qifuyin.

Results: Here we found that Qifuyin improved the ability of object recognition and memory, spatial learning and memory and conditional fear memory in CCL11-induced cognitive dysfunction of C57BL/6 mice. Qifuyin can improve synaptic plasticity, increase the expression of GAP-43, PSD-95 and SYN in the hippocampus of CCL11-induced mice. Cellular senescence of microglia and the amounts of SASP in the hippocampus were also reduced after Qifuyin treatment. Through the study of HMC3 cells with CCR3 gene knockout/overexpression, it was found that the brain components of Qifuyin could unlock the cell cycle arrest induced by CCL11/CCR3 pathway, reduce the proportion of G0 and G1 cells, reduce the expressions of p16, p21 and SASP, and enhance the synaptic connection of HT-22 cells damaged by HMC3 cells.

Conclusion: This study discovered that CCL11 precipitates microglia senescence in brain, resulting in synaptic structural damage and impaired neuronal functional plasticity, hence causing disruptions in learning and memory functions. Qifuyin can mitigate microglial senescence, safeguard synaptic plasticity, and enhance cognitive function.

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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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