title: Noradrenaline induces CX3CL1 production and release by neurons.
abstract: CX3CL1 is a chemokine for which neurons constitute its primary source within the brain. Besides acting as a chemokine, CX3CL1 regulates multiple processes and is known to inhibit microglial activation. Because of this, CX3CL1 is considered as a messenger used by neurons to communicate with microglia. Similarly, the neurotransmitter noradrenaline reduces microglial activation and production of neurotoxic agents. Based on this, the regulation of neuronal CX3CXL1 by noradrenaline was analyzed. In primary cortical neurons, noradrenaline induced the accumulation of CX3CL1 protein and mRNA. Noradrenaline also increased CX3CL1 in its soluble form despite the inhibition of the activity and synthesis of ADAM10 and ADAM17, the main proteases known to cleave CX3CL1 from the neuronal membrane. Noradrenaline-treated neurons displayed a higher degree of dendritic arborization and a characteristic accumulation of CX3CL1 in the dendritic bifurcation zones. The soluble CX3CL1 produced by neurons after noradrenaline treatment, reduced the accumulation of nitrites in microglia. These findings indicate that NA anti-inflammatory actions are mediated by neuronal CX3CL1. In addition, CX3CL1 seems to be involved in the development of neuronal processes stimulated by noradrenaline.
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Av. Complutense s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Investigación Neuroquímica and Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. Electronic address: jlmmadrigal@med.ucm.es.
authors.forename: José L M
authors.initials: JL
authors.lastname: Madrigal
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Av. Complutense s/n, 28040 Madrid, Spain; Department of Psychiatry, School of Medicine, Universidad Complutense de Madrid, Av. Complutense s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Investigación Neuroquímica and Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. Electronic address: jrcaso@med.ucm.es.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Caso
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Av. Complutense s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Investigación Neuroquímica and Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. Electronic address: bgbueno@med.ucm.es.
authors.forename: Borja
authors.initials: B
authors.lastname: García-Bueno
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Av. Complutense s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Investigación Neuroquímica and Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. Electronic address: irene.90@hotmail.com.
authors.forename: Irene L
authors.initials: IL
authors.lastname: Gutiérrez
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Av. Complutense s/n, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Investigación Neuroquímica and Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. Electronic address: jcleza@med.ucm.es.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism; D000072198:ADAM17 Protein / Q000378:metabolism; D000818:Animals; D054428:Chemokine CX3CL1 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000008:administration & dosage / Q000502:physiology*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism
chemical_list: D054428:Chemokine CX3CL1; D054360:Chemokine CXCL1; C515540:Cx3cl1 protein, rat; C513297:Cxcl1 protein, rat; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D000072197:ADAM10 Protein; C542371:ADAM10 protein, rat; D000072198:ADAM17 Protein; D009638:Norepinephrine
keywords: CX3CL1; Chemokine; Dibutyryl cAMP (PubChem CID: 9687); Fractalkine; ICI118551 (PubChem CID: 6324629); Isoproterenol (PubChem CID: 3779); Microglia; Neuron; Noradrenaline; TAPI-2 (PubChem CID: 10093303)