Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis

Brain Structure & Function
Luciana PinatoRegina Pekelmann Markus

Abstract

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...Continue Reading

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Citations

Oct 16, 2015·Expert Opinion on Therapeutic Targets·Jean A Boutin
Jan 7, 2016·Journal of Pineal Research·Luis Henrique Souza-TeodoroZ S Ferreira
Oct 30, 2015·Journal of Pineal Research·Gabriela S KinkerPedro A Fernandes
Aug 15, 2015·Sleep & Breathing = Schlaf & Atmung·Aline Rodrigues PintoLuciana Pinato
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Mar 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Annia GalanoRussel J Reiter
Jan 5, 2018·Neuroimmunomodulation·Leila Maria Guissoni CamposLuciana Pinato
Feb 27, 2018·Frontiers in Physiology·Leila M Guissoni CamposLuciana Pinato
Nov 7, 2017·British Journal of Pharmacology·Regina P MarkusMarina Marçola
Jul 15, 2017·British Journal of Pharmacology·Erika CeconRalf Jockers
Jul 30, 2019·Journal of Pineal Research·Leila Eliza Barbosa LimaPedro Augusto Carlos Magno Fernandes
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Jul 28, 2018·International Journal of Molecular Sciences·Marco A Pires-LapaRegina P Markus
Aug 8, 2018·International Journal of Molecular Sciences·Rosa Estrada-ReyesGloria Benítez-King
Jan 5, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·G S KinkerP A C M Fernandes
Jan 10, 2021·Journal of Pineal Research·Sanseray da Silveira Cruz-MachadoLuciana Pinato
Sep 23, 2021·Brain Structure & Function·Regina Markus

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Methods Mentioned

BETA
acetylation
nuclear translocation
ELISA
transgenic

Software Mentioned

Image
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