Fractalkine and CX 3CR1 regulate hippocampal neurogenesis in adult and aged rats

Adam D. Bachstetter, Josh M. Morganti, Jennifer Jernberg, Andrea Schlunk, Staten H. Mitchell, Kaelin W. Brewster, Charles E. Hudson, Michael J. Cole, Jeffrey K. Harrison, Paula C. Bickford, Carmelina Gemma

Research output: Contribution to journalArticlepeer-review

266 Citations (SciVal)

Abstract

Microglia have neuroprotective capacities, yet chronic activation can promote neurotoxic inflammation. Neuronal fractalkine (FKN), acting on CX 3CR1, has been shown to suppress excessive microglia activation. We found that disruption in FKN/CX 3CR1 signaling in young adult rodents decreased survival and proliferation of neural progenitor cells through IL-1β. Aged rats were found to have decreased levels of hippocampal FKN protein; moreover, interruption of CX 3CR1 function in these animals did not affect neurogenesis. The age-related loss of FKN could be restored by exogenous FKN reversing the age-related decrease in hippocampal neurogenesis. There were no measureable changes in young animals by the addition of exogenous FKN. The results suggest that FKN/CX 3CR1 signaling has a regulatory role in modulating hippocampal neurogenesis via mechanisms that involve indirect modification of the niche environment. As elevated neuroinflammation is associated with many age-related neurodegenerative diseases, enhancing FKN/CX 3CR1 interactions could provide an alternative therapeutic approach to slow age-related neurodegeneration.

Original languageEnglish
Pages (from-to)2030-2044
Number of pages15
JournalNeurobiology of Aging
Volume32
Issue number11
DOIs
StatePublished - Nov 2011

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (AG024165A CG: AG004418 PCB; AI058256 JKH), the VA Medical Research Service, and USF Signature Interdisciplinary Program in Neuroscience Research. Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, for use of confocal microscope. Amgen (Thousand Oaks, CA) provide the IL-1Ra as a kind gift.

Keywords

  • Aging
  • CX CR1
  • Fractalkine
  • Microglia
  • Neurogenesis
  • Neuroinflammation

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

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