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The chemokine stromal cell‐derived factor‐1/CXCL12 activates the nigrostriatal dopamine system
Author(s) -
Skrzydelski D.,
Guyon A.,
Daugé V.,
Rovère C.,
Apartis E.,
Kitabgi P.,
Nahon J. L.,
Rostène W.,
Parsadaniantz S. Mélik
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04639.x
Subject(s) - substantia nigra , neuroscience , striatum , microdialysis , dopaminergic , chemistry , dopamine , biology
We recently demonstrated that dopaminergic (DA) neurons of the rat substantia nigra constitutively expressed CXCR4, receptor for the chemokine stromal cell‐derived factor‐1 (SDF‐1)/CXCL12 (SDF‐1). To check the physiological relevance of such anatomical observation, in vitro and in vivo approaches were used. Patch clamp recording of DA neurons in rat substantia nigra slices revealed that SDF‐1 (10 nmol/L) induced: (i) a depolarization and increased action potential frequency; and (ii) switched the firing pattern of depolarized DA neurons from a tonic to a burst firing mode. This suggests that SDF‐1 could increase DA release from neurons. Consistent with this hypothesis, unilateral intranigral injection of SDF‐1 (50 ng) in freely moving rat decreased DA content and increased extracellular concentrations of DA and metabolites in the ipsilateral dorsal striatum, as shown using microdialysis. Furthermore, intranigral SDF‐1 injection induced a contralateral circling behavior. These effects of SDF‐1 were mediated via CXCR4 as they were abrogated by administration of a selective CXCR4 antagonist. Altogether, these data demonstrate that SDF‐1, via CXCR4, activates nigrostriatal DA transmission. They show that the central functions of chemokines are not restricted, as originally thought, to neuroinflammation, but extend to neuromodulatory actions on well‐defined neuronal circuits in non‐pathological conditions.