Chemokines and neuromodulation

https://doi.org/10.1016/j.jneuroim.2008.04.022Get rights and content

Abstract

Chemokines are not only mediators of the immune system and expressed in inflammatory situations. They are also constitutively expressed in the brain in both glial cells and neurons. Several recent evidence suggest that they can have a neurotransmitter/neuromodulatory role on brain functions similar to several neuropeptides reported so far. The aim of this short review is to illustrate that point using two chemokine systems, SDF-1/CXCL12 and its receptor CXCR4 and MCP-1/CCL2 and its receptor CCR2.

Section snippets

MCP-1/CCL2 expression in CNS

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is involved in the recruitment of cells of monocytic origin to sites of injury or inflammation (Fuentes et al., 1995, Gu et al., 1999). Several pieces of evidence suggest that MCP-1/CCL2 is an important mediator of the neuroinflammatory processes that takes place in various CNS diseases characterized by neuronal degeneration (Gerard and Rollins, 2001). Thus, its astroglial and/or microglial expression is increased in brain ischemia (Kim et al.,

CCR2 expression in CNS

Several studies showed that CCR2 is one of the most prominent chemokine receptors associated with neuroinflammatory pathologies such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) (Mahad and Ransohoff, 2003) or after chronic compression of the DRG (White et al., 2005). However, in a normal brain, little information was available on its expression by endogenous CNS cells. Neuronal expression of CCR2 was only observed in the hippocampal formation of human brain (

CXCR4 expression in CNS

CXCR4, the G protein-coupled receptor for SDF-1/CXCL12 is reported to have implications notably in brain development. (Ma et al., 1998, Zou et al., 1998). In addition, because CXCR4 serves as a HIV coreceptor (Feng et al., 1996), it was proposed that it could participate in HIV-induced neuronal death and dementia (Lavi et al., 1998). CXCR4-immunoreactivity was reported in cultures of human fetal neurons and astrocytes (Klein et al., 1999). It was shown in vitro that rat cultured neurons,

Conclusions and perspectives

As our knowledge about chemokines increases, it is becoming clear that chemokines are pivotal players in many biological functions, especially in neurobiology. It opens a new avenue in Neuroscience and increases the complexity of the various types of molecules involved in neurotransmission and neuron-glia interactions. Thus progress have to be done before taking into consideration the development and use of chemokine agonists or antagonists as pharmacological treatments in CNS pathology. Animal

Acknowledgements

Our work is supported by grants from l'Agence Nationale pour la Recherche (ANR) (R06282DS), the University Pierre and Marie Curie (Paris VI) and the Institut National de la Santé et de la Recherche Médicale (INSERM), France.

References (67)

  • OhtaniY. et al.

    Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells

    Neurosci. Lett.

    (1998)
  • OynebratenI. et al.

    Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments

    Blood

    (2004)
  • RagozzinoD. et al.

    Stimulation of chemokine CXC receptor 4 induces synaptic depression of evoked parallel fibers inputs onto Purkinje neurons in mouse cerebellum

    J. Neuroimmunol.

    (2002)
  • SimpsonJ.E. et al.

    Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions

    J. Neuroimmunol.

    (1998)
  • TanakaT. et al.

    Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain

    Neurosci. Res.

    (2004)
  • van der MeerP. et al.

    Immunohistochemical analysis of CCR2, CCR3, CCR5, and CXCR4 in the human brain: potential mechanisms for HIV dementia

    Exp. Mol. Pathol.

    (2000)
  • WestmorelandS.V. et al.

    Developmental expression patterns of CCR5 and CXCR4 in the rhesus macaque brain

    J. Neuroimmunol.

    (2002)
  • AbbadieC. et al.

    Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2

    Proc. Natl. Acad. Sci. U.S.A.

    (2003)
  • BajettoA. et al.

    Glial and neuronal cells express functional chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor 1

    J. Neurochem.

    (1999)
  • BanisadrG. et al.

    Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons

    Eur. J. Neurosci.

    (2002)
  • BanisadrG. et al.

    Highly regionalized neuronal expression of MCP-1/CCL2 in rat brain. Evidence for its colocalization with neurotransmitters and neuropeptides

    J. Comp. Neurol.

    (2005)
  • BanisadrG. et al.

    Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: functional effect of MCP-1/CCL2 on calcium mobilization in primary cultured neurons

    J. Comp. Neurol.

    (2005)
  • BanisadrG. et al.

    Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain

    J. Neurochem.

    (2002)
  • BanisadrG. et al.

    Highly regionalized distribution of stromal cell-derived factor-1/CXCL12 in adult rat brain: constitutive expression in cholinergic, dopaminergic and vasopressinergic neurons

    Eur. J. Neurosci.

    (2003)
  • BaronP. et al.

    Production of monocyte chemoattractant protein-1 in amyotrophic lateral sclerosis

    Muscle. Nerve.

    (2005)
  • CallewaereC. et al.

    The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4

    Proc. Natl. Acad. Sci. U.S.A.

    (2006)
  • CallewaereC. et al.

    Cellular and subcellular evidence for neuronal interaction between the chemokine stromal cell-derived factor-1/CXCL 12 and vasopressin: regulation in the hypothalamo-neurohypophysial system of the Brattleboro rats

    Endocrinology

    (2008)
  • CalvoC.F. et al.

    Production of monocyte chemotactic protein-1 by rat brain macrophages

    Eur. J. Neurosci.

    (1996)
  • ColobranR. et al.

    The chemokine network. I. How the genomic organization of chemokines contains clues for deciphering their functional complexity

    Clin. Exp. Immunol.

    (2007)
  • ColobranR. et al.

    The chemokine network. II. On how polymorphisms and alternative splicing increase the number of molecular species and configure intricate patterns of disease susceptibility

    Clin. Exp. Immunol.

    (2007)
  • Dansereau, M.A., Gosselin, R.D., Pohl, M., Pommier, B., Mechighel, P., Mauborgne, A., Rostene, W., Kitabgi, P.,...
  • de JongE.K. et al.

    Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion

    J. Neurosci.

    (2005)
  • FengY. et al.

    HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor

    Science

    (1996)
  • Cited by (0)

    View full text