title: The chemokine CXCL16 modulates neurotransmitter release in hippocampal CA1 area.
abstract: Chemokines have several physio-pathological roles in the brain. Among them, the modulation of synaptic contacts and neurotransmission recently emerged as crucial activities during brain development, in adulthood, upon neuroinflammation and neurodegenerative diseases. CXCL16 is a chemokine normally expressed in the brain, where it exerts neuroprotective activity against glutamate-induced damages through cross communication with astrocytes and the involvement of the adenosine receptor type 3 (A3R) and the chemokine CCL2. Here we demonstrated for the first time that CXCL16 exerts a modulatory activity on inhibitory and excitatory synaptic transmission in CA1 area. We found that CXCL16 increases the frequency of the miniature inhibitory synaptic currents (mIPSCs) and the paired-pulse ratio (PPR) of evoked IPSCs (eIPSCs), suggesting a presynaptic modulation of the probability of GABA release. In addition, CXCL16 increases the frequency of the miniature excitatory synaptic currents (mEPSCs) and reduces the PPR of evoked excitatory transmission, indicating that the chemokine also modulates and enhances the release of glutamate. These effects were not present in the A3RKO mice and in WT slices treated with minocycline, confirming the involvement of A3 receptors and introducing microglial cells as key mediators of the modulatory activity of CXCL16 on neurons.
authors.affiliation: Istituto Pasteur-Italia, Dipartimento di Fisiologia e Farmacologia, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Maria Amalia
authors.initials: MA
authors.lastname: Di Castro
authors.affiliation: Istituto Pasteur-Italia, Dipartimento di Fisiologia e Farmacologia, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Trettel
authors.affiliation: Istituto Pasteur-Italia, Dipartimento di Fisiologia e Farmacologia, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Milior
authors.affiliation: Istituto Pasteur-Italia, Dipartimento di Fisiologia e Farmacologia, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Maggi
authors.affiliation: Dipartimento di Fisiologia e Farmacologia, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.|Neuromed I.R.C.C.S., Via Atinese 18, 86077 Pozzilli (IS), Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Ragozzino
authors.affiliation: Istituto Pasteur-Italia, Dipartimento di Fisiologia e Farmacologia, Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.|Neuromed I.R.C.C.S., Via Atinese 18, 86077 Pozzilli (IS), Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Limatola
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D000075743:Chemokine CXCL16 / Q000235:genetics / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008911:Minocycline / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D000075743:Chemokine CXCL16; C498926:Cxcl16 protein, mouse; D018377:Neurotransmitter Agents; D043684:Receptor, Adenosine A3; D018698:Glutamic Acid; D008911:Minocycline