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SDF-1α-mediated modulation of synaptic transmission in rat cerebellum

Authors

  • Cristina Limatola,

    1. Dipartimento Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, Viale Regina Elena 324, I00161 Roma, Italy
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    • *C.L., A.G., L.M., D.R., L.C. and M.T.C. contributed equally to this work.
  • Aldo Giovannelli,

    1. Dipartimento Medicina Sperimentale Coppito, I63100 L'Aquila, Italy
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    • *C.L., A.G., L.M., D.R., L.C. and M.T.C. contributed equally to this work.
  • Laura Maggi,

    1. Dipartimento Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, Viale Regina Elena 324, I00161 Roma, Italy
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    • *C.L., A.G., L.M., D.R., L.C. and M.T.C. contributed equally to this work.
  • Davide Ragozzino,

    1. Dipartimento Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, Viale Regina Elena 324, I00161 Roma, Italy
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    • *C.L., A.G., L.M., D.R., L.C. and M.T.C. contributed equally to this work.
  • Loriana Castellani,

    1. Dipartimento di Neuroscienze and INFM sez. B, Università di Tor Vergata Roma, Italy
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    • *C.L., A.G., L.M., D.R., L.C. and M.T.C. contributed equally to this work.
  • Maria Teresa Ciotti,

    1. Istituto di Neurobiologia Consiglio Nazionale delle Ricerche viale C. Marx Roma, Italy
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    • *C.L., A.G., L.M., D.R., L.C. and M.T.C. contributed equally to this work.
  • Fabrizio Vacca,

    1. Dipartimento Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, Viale Regina Elena 324, I00161 Roma, Italy
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  • Delio Mercanti,

    1. Istituto di Neurobiologia Consiglio Nazionale delle Ricerche viale C. Marx Roma, Italy
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  • Angela Santoni,

    1. Dipartimento Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, Viale Regina Elena 324, I00161 Roma, Italy
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  • Fabrizio Eusebi

    1. Dipartimento Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, Viale Regina Elena 324, I00161 Roma, Italy
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: Dr C. Limatola, as above.
E-mail: limatola@axrma.uniroma1.it

Abstract

The functional expression of the seven-transmembrane domain G protein-coupled chemokine receptor CXCR-4/fusin in rat nerve cell was demonstrated by staining with a polyclonal anti-CXCR-4 Ab, and by evaluating the calcium responses to the physiological agonist stromal-derived cell factor-1α (SDF-1α) in both cerebellar granule cells in culture and Purkinje neurons (PNs) in cerebellar slices. Cerebellar glial, granule and Purkinje cells showed a pronounced staining for CXCR-4. Furthermore, cultured granule cells exhibited Ca2+ transients elicited by the application of SDF-1α, both in cell bodies and in neuronal processes. Whole-cell patch-clamped PNs in cerebellar slices responded to SDF-1α application by a slow inward current followed by an increase of both intracellular Ca2+ level and spontaneous synaptic activity. In particular, the SDF-1α-induced slow inward current was considerably reduced by ionotropic glutamate receptor blockers, but developed fully in a medium in which synaptic transmission was inhibited, indicating that this current might be, at least in part, mediated by extrasynaptic glutamate, possibly released from the surrounding glial and/or nerve cells. Taken together, these findings indicate a functional involvement of CXCR-4 in the modulation of synaptic transmission, adding another member to the repertoire of the chemokine receptors exerting a neuromodulatory role in the cerebellum.

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