Alteration in peritoneal cells with the chemokine CX3CL1 reverses age-associated impairment of recognition memory

Geroscience. 2022 Aug;44(4):2305-2318. doi: 10.1007/s11357-022-00579-3. Epub 2022 May 20.

Abstract

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 p16INK4a 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.

Keywords: BDNF; Novel object recognition; Peritoneal cells; Rejuvenation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor* / genetics
  • Chemokine CX3CL1* / metabolism
  • Cognition
  • Hippocampus / metabolism
  • Mice
  • Recognition, Psychology / physiology

Substances

  • Brain-Derived Neurotrophic Factor
  • Chemokine CX3CL1
  • Cx3cl1 protein, mouse