Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity

Limatola, Cristina; Lauro, Clotilde; Catalano, Myriam; Ciotti, Maria Teresa; Bertollini, Cristina; Angelantonio, Silvia Di; Ragozzino, Davide; Eusebi, Fabrizio

doi:10.1016/j.jneuroim.2005.03.023

Cited by 139 publications

(142 citation statements)

References 42 publications

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“…This corresponded to about 70% of total neuronal loss on Glu treatment, as assessed by immunofluorescence analysis with b-tubulin III staining (data not shown). We confirm, in this manuscript, that CX3CL1 protects hippocampal neurons from Glu-induced excitotoxicity ( Figure 1a) similarly to what already shown in neuronal preparations, which contain different ratios of neurons:astrocytes:microglia (Limatola et al, 2005;Lauro et al, 2008). Given that CX3CR1 are predominantly expressed in microglial cells, it is likely that microglial cells mediate the neurotrophic effect of CX3CL1.…”

Section: Microglia Depletion With Clodronate Liposomes Impairs the Nesupporting

confidence: 89%

“…No significant differences in neuron death were observed between wt and CX3CL1 À/À mice at all tested Glu concentrations (Supplementary Figure S2). This suggests that endogenous levels of CX3CL1, neither before nor after Glu treatment (Chapman et al, 2000;Erichsen et al, 2003;Limatola et al, 2005), are sufficient to protect neurons by excitotoxicity under our in vitro conditions. To analyze whether the effect of the administration of the soluble form of CX3CL1 could be different in wt vs CX3CL1 À/À mice, evidencing a possible cooperative role of the endogenous CX3CL1, excitotoxicity experiments were performed as shown in Figure 2.…”

Section: Hippocampal Neurons From Cx3cl1 à/à Mice Are Not More Vulnermentioning

confidence: 78%

“…It is interesting to note how a few percentage of microglial cells (such as that present in our hippocampal neuronal preparation) can massively influence neuronal response to CX3CL1. This could explain the reported neuroprotective effect of CX3CL1 in almost pure neuronal cultures (Limatola et al, 2005).…”

Section: Discussionmentioning

confidence: 91%

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Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Lauro

Cipriani

Catalano

et al. 2010

Neuropsychopharmacol

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110

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Fractalkine/CX3CL1 is a neuron-associated chemokine, which modulates microglia-induced neurotoxicity activating the specific and unique receptor CX3CR1. CX3CL1/CX3CR1 interaction modulates the release of cytokines from microglia, reducing the level of tumor necrosis factor-a, interleukin-1-b, and nitric oxide and induces the production of neurotrophic substances, both in vivo and in vitro. We have recently shown that blocking adenosine A 1 receptors (A 1 R) with the specific antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) abolishes CX3CL1-mediated rescue of neuronal excitotoxic death and that CX3CL1 induces the release of adenosine from microglia. In this study, we show that the presence of extracellular adenosine is mandatory for the neurotrophic effect of CX3CL1 as reducing adenosine levels in hippocampal cultures, by adenosine deaminase treatment, strongly impairs CX3CL1-mediated neuroprotection. Furthermore, we confirm the predominant role of microglia in mediating the neuronal effects of CX3CL1, because the selective depletion of microglia from hippocampal cultures treated with clodronate-filled liposomes causes the complete loss of effect of CX3CL1. We also show that hippocampal neurons obtained from A 1 R À/À mice are not protected by CX3CL1 whereas A 2A R À/À neurons are. The requirement of functional A 1 R for neuroprotection is not unique for CX3CL1 as A 1 R À/À hippocampal neurons are not rescued from Glu-induced cell death by other neurotrophins such as brain-derived neurotrophic factor and erythropoietin, which are fully active on wt neurons.

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Section: Microglia Depletion With Clodronate Liposomes Impairs the Nesupporting

confidence: 89%

Section: Hippocampal Neurons From Cx3cl1 à/à Mice Are Not More Vulnermentioning

confidence: 78%

See 1 more Smart Citation

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Lauro

Cipriani

Catalano

et al. 2010

Neuropsychopharmacol

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110

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“…The function of leukocytes in the injured mammalian inner ear and the cues that regulate their activation are poorly understood at this time. In the central nervous system, CX3CL1 and CX3CR1 have been shown to modulate microglial activation and neurotoxicity in various conditions of brain injury (Harrison et al 1998;Limatola et al 2005a;Cardona et al 2006). Our current study confirms high frequency hearing loss and degeneration of high frequency outer hair cells in mammals exposed to kanamycin (Henry et al 1981;Chen and Saunders 1983;Wu et al 2001;Jiang et al 2006;Taleb et al 2009).…”

Section: Discussionsupporting

confidence: 78%

“…Its ligand, fractalkine, is a membrane-bound glycoprotein expressed on neurons and endothelial cells and acts as a potent adhesion molecule. Fractalkine is also found in a soluble form and has been shown to modulate activated microglia in the central nervous system (Limatola et al 2005b;Cardona et al 2006;Lauro et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Expression of Fractalkine Receptor CX3CR1 on Cochlear Macrophages Influences Survival of Hair Cells Following Ototoxic Injury

Sato

Shick

Ransohoff

et al. 2009

JARO

112

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The role of innate immunity and macrophage recruitment to the inner ear after hair cell injury is a subject where little is known. In this paper, we demonstrate recruitment of monocytes and macrophages to the inner ear after kanamycin. We also examined the effect of fractalkine receptor (CX3CR1) deletion in kanamycin ototoxicity. We observed more functional and structural damage in CX3CR1 null mice compared to wild-type and heterozygous littermates. In order to determine if increased susceptibility to kanamycin resulted from CX3CR1 deletion from cochlear leukocytes, we created bone marrow chimeras by transplanting CX3CR1-null bone marrow into wild-type mice whose native bone marrow was ablated by lethal irradiation. These mice were then treated with kanamycin sulfate. Auditory brainstem responses (ABR), hair cell counts, and numbers of macrophages recruited to the cochlea were recorded in irradiated mice that received either wild-type, CX3CR1 heterozygous, or CX3CR1 knockout bone marrow. A strong correlation was present between numbers of macrophages and hair cell death in recipients transplanted with CX3CR1 null marrow. No correlation between macrophage number and hair cell loss was present in mice transplanted with wild-type or CX3CR1 heterozygous marrow. We suggest that CX3CR1 plays a role in modulating the detrimental effects of cochlear macrophages after kanamycin ototoxicity. Our data point to the possibility that CX3CR1-deficient cochlear macrophages exacerbate kanamycin ototoxicity while CX3CR1-expressing monocytes do not.

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CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia

Parajuli

Horiuchi

Mizuno

et al. 2015

Glia

122

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The chemokine CCL11 (also known as eotaxin-1) is a potent eosinophil chemoattractant that mediates allergic diseases such as asthma, atopic dermatitis, and inflammatory bowel diseases. Previous studies demonstrated that concentrations of CCL11 are elevated in the sera and cerebrospinal fluids (CSF) of patients with neuroinflammatory disorders, including multiple sclerosis. Moreover, the levels of CCL11 in plasma and CSF increase with age, and CCL11 suppresses adult neurogenesis in the central nervous system (CNS), resulting in memory impairment. However, the precise source and function of CCL11 in the CNS are not fully understood. In this study, we found that activated astrocytes release CCL11, whereas microglia predominantly express the CCL11 receptor. CCL11 significantly promoted the migration of microglia, and induced microglial production of reactive oxygen species by upregulating nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), thereby promoting excitotoxic neuronal death. These effects were reversed by inhibition of NOX1. Our findings suggest that CCL11 released from activated astrocytes triggers oxidative stress via microglial NOX1 activation and potentiates glutamate-mediated neurotoxicity, which may be involved in the pathogenesis of various neurological disorders.

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Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity

Cited by 139 publications

References 42 publications

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Expression of Fractalkine Receptor CX3CR1 on Cochlear Macrophages Influences Survival of Hair Cells Following Ototoxic Injury

CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia

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