Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Geroscience. 2022 Aug;44(4):2305-2318. doi: 10.1007/s11357-022-00579-3. Epub 2022 May 20.
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 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.
认知功能随年龄增长逐渐下降。肥胖会促进衰老过程，而运动则可以减弱这种过程。这两种情况都会影响外周组织中趋化因子 CX3CL1 的水平；然而，其在认知衰老中的作用尚不清楚。在当前的研究中，我们将 CX3CL1 注入老年小鼠的腹腔，以研究其对衰老过程的影响。在腹腔中，CX3CL1 不仅逆转了与年龄相关的表达衰老标志物 p16 的细胞积累，还增加了腹腔吞噬活性，表明 CX3CL1 影响了腹腔细胞的表型。在老年小鼠的海马体中，腹腔内给予 CX3CL1 增加了 Type-2 神经干细胞的数量，并促进了脑源性神经营养因子 (BDNF) 的表达。这种治疗方法还改善了随年龄增长而受损的新物体识别记忆。来自接受 CX3CL1 治疗的老年小鼠的腹腔细胞的腹腔内移植改善了受体老年小鼠的新物体识别记忆。这表明腹腔细胞在 CX3CL1 诱导的老年小鼠识别记忆改善中起关键作用。迷走神经切断术抑制了 CX3CL1 诱导的 BDNF 表达增加，表明迷走神经参与了腹腔内给予 CX3CL1 诱导的海马体 BDNF 表达。因此，我们的结果表明，腹腔细胞、迷走神经和海马体之间的新联系可以逆转与年龄相关的识别记忆下降。
