Chemokines and neuromodulation
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.
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