Alteration in peritoneal cells with the chemokine CX3CL1 reverses age-associated impairment of recognition memory
Alteration in peritoneal cells with the chemokine CX3CL1 reverses age-associated impairment of recognition memory
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DOI：
10.1007/s11357-022-00579-3
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发表时间：
2022-05-20
期刊：
影响因子：
5.6
通讯作者：
Hirasawa, Akira
中科院分区：
文献类型：
--
作者：
Takei, Yoshinori;Amagase, Yoko;Hirasawa, Akira
认知功能随着年龄的增长而逐渐下降。肥胖可以促进衰老过程，而运动可以减缓衰老过程。这两种情况都会影响外周组织中趋化因子CX 3CL 1的水平;然而，其在认知衰老中的作用尚不清楚。在目前的研究中，我们将CX 3CL 1注入老年小鼠的腹腔，以研究其对衰老过程的影响。在腹膜腔中，CX 3CL 1不仅逆转了表达衰老标记物p16（INK 4a）的细胞的年龄相关积累，而且还增加了腹膜吞噬活性，表明CX 3CL 1影响了腹膜细胞的表型。在老龄小鼠海马中，腹腔注射CX 3CL 1增加了2型神经干细胞的数量，并促进脑源性神经营养因子（BDNF）的表达。此外，这种治疗改善了随着年龄增长而受损的新物体识别记忆。CX 3CL 1处理的老年小鼠的腹膜细胞腹膜内移植改善了受体老年小鼠的新物体识别记忆。这表明腹膜细胞在CX 3CL 1诱导的老年小鼠识别记忆改善中具有关键作用。迷走神经切断术抑制了CX 3CL 1诱导的BDNF表达的增加，表明迷走神经参与了腹腔内注射CX 3CL 1诱导的海马BDNF表达。因此，我们的研究结果表明，腹膜细胞，迷走神经和海马之间的一种新的连接可以逆转与年龄相关的识别记忆下降。
Cognitive function progressively declines with advancing age. The aging process can be promoted by obesity and attenuated by exercise. Both conditions affect levels of the chemokine CX3CL1 in peripheral tissues; however, its role in cognitive aging is unknown. In the current study, we administered CX3CL1 into the peritoneal cavity of aged mice to investigate its impact on the aging process. In the peritoneal cavity, CX3CL1 not only reversed the age-associated accumulation of cells expressing the senescence marker p16(INK4a) but also increased peritoneal phagocytic activity, indicating that CX3CL1 affected the phenotypes of peritoneal cells. In the hippocampus of aged mice, intraperitoneal administration of CX3CL1 increased the number of Type-2 neural stem cells and promoted brain-derived neurotrophic factor (BDNF) expression. This treatment, furthermore, improved novel object recognition memory impaired with advancing age. Intraperitoneal transplantation of peritoneal cells from CX3CL1-treated aged mice improved novel object recognition memory in recipient aged mice. It indicates that peritoneal cells have a critical role in the CX3CL1-induced improvement of recognition memory in aged mice. Vagotomy inhibited the CX3CL1-induced increase in BDNF expression, demonstrating that the vagus nerve is involved in the hippocampal BDNF expression induced by intraperitoneal administration of CX3CL1. Thus, our results demonstrate that a novel connection among the peritoneal cells, the vagus nerve, and the hippocampus can reverse the age-associated decline in recognition memory.