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Chemokines: a new class of neuromodulator?

Abstract

Chemokines are not only found in the immune system or expressed in inflammatory conditions: they are constitutively present in the brain in both glial cells and neurons. Recently, the possibility has been raised that they might act as neurotransmitters or neuromodulators. Although the evidence is incomplete, emerging data show that chemokines have several of the characteristics that define neurotransmitters. Moreover, their physiological actions resemble those of neuromodulators in the sense that chemokines usually have few effects by themselves in basal conditions, but modify the induced release of neurotransmitters or neuropeptides. These findings, together with the pharmacological development of agonists and antagonists that are selective for chemokine receptors and can cross the blood–brain barrier, open a new era of research in neuroscience.

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Figure 1: The neuroanatomical localization of CCL2 and its receptor, CCR2, in the normal adult rat brain.
Figure 2: CCL21 immunoreactivity in presynaptic nerve terminals of cultured mouse cortical neurons.
Figure 3: Colocalization of CCL2 and CCR2 proteins with 'classical' neurotransmitters and with neuropeptides and neurohormones in the adult rat brain.
Figure 4: The modulation by CCL2 of the GABA-induced electrical response on cultured spinal-cord neurons of the adult rat.
Figure 5: The effect of CXCL12 on rat hippocampal neuron morphology.
Figure 6: CXCL12 in the rat substantia nigra induces striatal dopamine release and contralateral circling behaviour.
Figure 7: The different modes of action of neuronal chemokines in the brain.

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Acknowledgements

Many thanks to G. Banisadr, C. Callewaere, R. Gosselin and D. Skrzydelski, and several of our collaborators, for the data they brought in the laboratory, which allowed us to support some of the hypotheses raised in this paper.

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Rostène, W., Kitabgi, P. & Parsadaniantz, S. Chemokines: a new class of neuromodulator?. Nat Rev Neurosci 8, 895–903 (2007). https://doi.org/10.1038/nrn2255

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