Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats.
Microglia have neuroprotective capacities, yet chronic activation can promote neurotoxic inflammation. Neuronal fractalkine (FKN), acting on CX(3)CR1, has been shown to suppress excessive microglia activation. We found that disruption in FKN/CX(3)CR1 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(3)CR1 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(3)CR1 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(3)CR1 interactions could provide an alternative therapeutic approach to slow age-related neurodegeneration.
Bachstetter
Adam D
AD
Department of Molecular Pharmacology and Physiology, University of South Florida, College of Medicine, Tampa, FL 33612, USA.
Morganti
Josh M
JM
Jernberg
Jennifer
J
Schlunk
Andrea
A
Mitchell
Staten H
SH
Brewster
Kaelin W
KW
Hudson
Charles E
CE
Cole
Michael J
MJ
Harrison
Jeffrey K
JK
Bickford
Paula C
PC
Gemma
Carmelina
C
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1; D053583:Interleukin-1beta; D019707:Receptors, Chemokine