Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats

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

doi:10.1016/j.neurobiolaging.2009.11.022

Cited by 309 publications

(321 citation statements)

References 47 publications

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“…In line with Bachstetter et al (2011), we confirmed reduced hippocampal neurogenesis in 2-month-old KO mice. An ϳ25% decrease in the density of BrdU pos cells ( p ϭ 0.032) (Fig.…”

Section: Is Cx3cl1 Involved In Regulating Microglia-dependent Precurssupporting

confidence: 84%

“…Experimental mice received 5 g of ␣-CX 3 CR1 (Torrey Pines Biolabs; n ϭ 8) (Bachstetter et al, 2011) or control IgG (Sigma-Aldrich; n ϭ 6 animals) per day (flow rate of 0.11 l/h) over a 2 week period, during which time the animals had access to a running wheel. After completion of the infusion period, the mice were killed, hippocampi were dissected, and cell preparations from two animals were pooled for each experimental repeat.…”

Section: Intraparenchymal Infusion Of CX 3 Cr1 Blocking Antibodymentioning

confidence: 99%

“…Previous reports have highlighted that signaling through the CX 3 CR1-CX 3 CL1 axis results in more neuroprotective microglia (Cardona et al, 2006), with positive modulation of hippocampal neurogenesis (Bachstetter et al, 2011). Using double-immunofluorescent staining procedures, we found that the total number of BrdU pos (i.e., proliferating) microglia was increased in the hippocampus of runner wild-type mice (runner: 15.50 Ϯ 3.78 cells; nonrunner: 4.00 Ϯ 0.91 cells; n ϭ 4 per group; p ϭ 0.03), which is similar to the observations of Olah et al (2009).…”

Section: Is Cx3cl1 Involved In Regulating Microglia-dependent Precursmentioning

confidence: 99%

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Microglia Modulate Hippocampal Neural Precursor Activity in Response to Exercise and Aging

Vukovic¹,

Colditz²,

Blackmore³

et al. 2012

J. Neurosci.

206

184

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Exercise has been shown to positively augment adult hippocampal neurogenesis; however, the cellular and molecular pathways mediating this effect remain largely unknown. Previous studies have suggested that microglia may have the ability to differentially instruct neurogenesis in the adult brain. Here, we used transgenic Csf1r-GFP mice to investigate whether hippocampal microglia directly influence the activation of neural precursor cells. Our results revealed that an exercise-induced increase in neural precursor cell activity was mediated via endogenous microglia and abolished when these cells were selectively removed from hippocampal cultures. Conversely, microglia from the hippocampi of animals that had exercised were able to activate latent neural precursor cells when added to neurosphere preparations from sedentary mice. We also investigated the role of CX 3 CL1, a chemokine that is known to provide a more neuroprotective microglial phenotype. Intraparenchymal infusion of a blockingantibodyagainsttheCX 3 CL1receptor,CX 3 CR1,butnotcontrolIgG,dramaticallyreducedtheneurosphereformationfrequencyinmice thathadexercised.WhileanincreaseinsolubleCX 3 CL1wasobservedfollowingrunning,reducedlevelsofthischemokinewerefoundintheaged brain.LowerlevelsofCX 3 CL1withadvancingagecorrelatedwiththenaturaldeclineinneuralprecursorcellactivity,astatethatcouldbepartially alleviated through removal of microglia. These findings provide the first direct evidence that endogenous microglia can exert a dual and opposing influence on neural precursor cell activity within the hippocampus, and that signaling through the CX 3 CL1-CX 3 CR1 axis critically contributes toward this process.

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“…In line with Bachstetter et al (2011), we confirmed reduced hippocampal neurogenesis in 2-month-old KO mice. An ϳ25% decrease in the density of BrdU pos cells ( p ϭ 0.032) (Fig.…”

Section: Is Cx3cl1 Involved In Regulating Microglia-dependent Precurssupporting

confidence: 84%

Section: Intraparenchymal Infusion Of CX 3 Cr1 Blocking Antibodymentioning

confidence: 99%

Section: Is Cx3cl1 Involved In Regulating Microglia-dependent Precursmentioning

confidence: 99%

See 1 more Smart Citation

Microglia Modulate Hippocampal Neural Precursor Activity in Response to Exercise and Aging

Vukovic¹,

Colditz²,

Blackmore³

et al. 2012

J. Neurosci.

206

184

View full text Add to dashboard Cite

show abstract

“…Additional studies have shown that this relates to activated microglia, supporting the anti-inflammatory fractalkine-CX3CR1 signaling has been shown to regulate neurogenesis, with exogenous fractalkine being able action of hUCBCs (70,71). As well as changes in microglia, the peripheral number of lymphocytes was into restore the age-related decrease in neurogenesis observed in aged rats (6). Modification of this signaling creased, whereas neutrophils were decreased in mice given the optimal dose, suggesting that the "immune depathway has also been shown in APP transgenic mice (23) and in AD patients (55).…”

Section: Introductionmentioning

confidence: 96%

“…A significantly reduced number of microglia was detected (3,7,42). However, there is an age-related loss of fractalkine, meaning that microglia are more likely to become in mice treated with the optimal number of hUCBCs compared with untreated mice and those given a differactivated with time and this could become excessive and eventually cause neural damage (6). In addition, the ent dose.…”

Section: Introductionmentioning

confidence: 99%

The Treatment of Neurodegenerative Disorders Using Umbilical Cord Blood and Menstrual Blood-Derived Stem Cells

et al. 2011

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Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual bloodderived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

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