caa a22 4500 606203230 CHVBK 20210128100956.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s00429-013-0686-4 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0686-4 Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis [Elektronische Daten] [Luciana Pinato, Sanseray da Silveira Cruz-Machado, Daiane Franco, Leila Campos, Erika Cecon, Pedro Fernandes, Jackson Bittencourt, Regina Markus] Although melatonin is mainly produced by the pineal gland, an increasing number of extra-pineal sites of melatonin synthesis have been described. We previously demonstrated the existence of bidirectional communication between the pineal gland and the immune system that drives a switch in melatonin production from the pineal gland to peripheral organs during the mounting of an innate immune response. In the present study, we show that acute neuroinflammation induced by lipopolysaccharide (LPS) injected directly into the lateral ventricles of adult rats reduces the nocturnal peak of melatonin in the plasma and induces its synthesis in the cerebellum, though not in the cortex or hippocampus. This increase in cerebellar melatonin content requires the activation of nuclear factor kappa B (NF-κB), which positively regulates the expression of the key enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT). Interestingly, LPS treatment led to neuronal death in the hippocampus and cortex, but not in the cerebellum. This privileged protection of cerebellar cells was abrogated when G-protein-coupled melatonin receptors were blocked by the melatonin antagonist luzindole, suggesting that the local production of melatonin protects cerebellar neurons from LPS toxicity. This is the first demonstration of a switch between pineal and extra-pineal melatonin production in the central nervous system following a neuroinflammatory response. These results have direct implications concerning the differential susceptibility of specific brain areas to neuronal death. The Author(s), 2013 Pineal gland nationallicence Arylalkylamine N -acetyltransferase (AA-NAT) nationallicence Immune-pineal axis nationallicence Neuroinflammation nationallicence Melatonin receptors nationallicence Nuclear factor kappa B (NF-κB) nationallicence Pinato Luciana Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut da Silveira Cruz-Machado Sanseray Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut Franco Daiane Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut Campos Leila Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo (USP), 05508-900, São Paulo, SP, Brazil aut Cecon Erika Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut Fernandes Pedro Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut Bittencourt Jackson Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo (USP), 05508-900, São Paulo, SP, Brazil aut Markus Regina Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 827-840 1863-2653 220:2<827 2015 220 429 https://doi.org/10.1007/s00429-013-0686-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0686-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pinato Luciana Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- da Silveira Cruz-Machado Sanseray Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Franco Daiane Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Campos Leila Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo (USP), 05508-900, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Cecon Erika Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Fernandes Pedro Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Bittencourt Jackson Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo (USP), 05508-900, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Markus Regina Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 827-840 1863-2653 220:2<827 2015 220 429