JNJ10181457, a histamine H3 receptor inverse agonist, regulates in vivo microglial functions and improves depression-like behaviours in mice

Biochemical and Biophysical Research Communications
Tomomitsu IidaKazuhiko Yanai

Abstract

Brain histamine acts as a neurotransmitter and regulates various physiological functions, such as learning and memory, sleep-wake cycles, and appetite regulation. We have recently shown that histamine H3 receptor (H3R) is expressed in primary mouse microglia and has a strong influence on critical functions in microglia, including chemotaxis, phagocytosis, and cytokine secretion in vitro. However, the importance of H3R in microglial activity in vivo remains unknown. Here, we examined the effects of JNJ10181457 (JNJ), a selective and potent H3R inverse agonist, on microglial functions ex vivo and in vivo. First, we injected ATP, which is a typical chemoattractant, into hippocampal slices to investigate the effect of JNJ on chemotaxis. ATP-induced microglial migration toward the injected site was significantly suppressed by JNJ treatment. Next, we examined whether JNJ affected microglial phagocytosis in hippocampal slices and in the prefrontal cortex. Microglial engulfment of dead neurons induced by N-methyl-d-aspartate was inhibited in the presence of JNJ. The increase in zymosan particle uptake by activated microglia in the prefrontal cortex was prevented by JNJ administration. Finally, we determined the importance of JNJ in a l...Continue Reading

References

Jan 1, 1982·Psychopharmacology·C NathK P Bhargava
Jul 4, 1998·Trends in Pharmacological Sciences·R LeursH Timmerman
Feb 4, 2003·Nature Reviews. Neuroscience·Helmut Haas, Pertti Panula
May 17, 2005·Nature Neuroscience·Dimitrios DavalosWen-Biao Gan
Nov 30, 2006·Biochemical Pharmacology·P BonaventureT Lovenberg
Apr 6, 2007·Nature·Schuichi KoizumiKazuhide Inoue
May 10, 2007·Nature Protocols·Astrid E CardonaRichard M Ransohoff
Mar 18, 2008·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·K AlesM Lipnik-Stangelj
Jun 24, 2008·Brain : a Journal of Neurology·H NeumannR J M Franklin
Jul 16, 2008·Physiological Reviews·Helmut L HaasOliver Selbach
May 7, 2009·Journal of Neurochemistry·Christoph D SchmidMonica J Carson
Jul 24, 2010·British Journal of Pharmacology·J C McGrathC L Wainwright
Dec 21, 2010·Neuropathology and Applied Neurobiology·E ZotovaD Boche
Feb 1, 2011·Neuropharmacology·Damijana M JuričMarija Carman-Kržan
Sep 10, 2011·The Journal of Biological Chemistry·Urte NeniskyteGuy C Brown
Dec 27, 2011·Brain, Behavior, and Immunity·Grietje KrabbeHelmut Kettenmann
Feb 22, 2012·Journal of Psychiatry & Neuroscience : JPN·Patricia Boksa
Apr 4, 2013·The Journal of Biological Chemistry·Stefka Gyoneva, Stephen F Traynelis
Aug 14, 2013·PloS One·Corey M WebsterMidori A Yenari
Mar 22, 2014·Nature Reviews. Neuroscience·Guy C Brown, Jonas J Neher

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Citations

Aug 16, 2018·British Journal of Pharmacology·Gustavo ProvensiPatrizio Blandina
Oct 9, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Jian XinSong Wu
Jan 18, 2018·Expert Opinion on Therapeutic Patents·Dorota Łażewska, Katarzyna Kieć-Kononowicz
Aug 4, 2020·British Journal of Pharmacology·Takeo YoshikawaKazuhiko Yanai
Jun 12, 2019·Scientific Reports·Cláudia SaraivaLiliana Bernardino
Jul 16, 2021·The European Journal of Neuroscience·Melinda HerseyLawrence P Reagan

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