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

doi:10.1016/j.neurobiolaging.2009.11.022

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

Producción científica: Article › revisión exhaustiva

313 Citas (SciVal)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	2030-2044
Número de páginas	15
Publicación	Neurobiology of Aging
Volumen	32
N.º	11
DOI	https://doi.org/10.1016/j.neurobiolaging.2009.11.022
Estado	Published - nov 2011

Nota bibliográfica

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.

Financiación

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.

Financiadores	Número del financiador
VA Medical Research Service
National Institutes of Health (NIH)	AG004418, AI058256 JKH
National Institute on Aging	R21AG024165
University of California San Francisco

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

Acceder al documento

10.1016/j.neurobiolaging.2009.11.022

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title = "Fractalkine and CX 3CR1 regulate hippocampal neurogenesis in adult and aged rats",

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.",

keywords = "Aging, CX CR1, Fractalkine, Microglia, Neurogenesis, Neuroinflammation",

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

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. ",

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AU - Morganti, Josh M.

AU - Jernberg, Jennifer

AU - Schlunk, Andrea

AU - Mitchell, Staten H.

AU - Brewster, Kaelin W.

AU - Hudson, Charles E.

AU - Cole, Michael J.

AU - Harrison, Jeffrey K.

AU - Bickford, Paula C.

AU - Gemma, Carmelina

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PY - 2011/11

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N2 - 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.

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