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Article: M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus

TitleM30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus
Authors
Issue Date2016
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2016, v. 11 n. 11, p. e0166966:1-23 How to Cite?
AbstractMonoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT). Sprague-Dawley rats were given CORT subcutaneous injections with or without concomitant M30 administration for two weeks. CORT-treated rats exhibited depressive-like behavior with significant elevated levels of MAO activities, serotonin turnover, oxidative stress, neuroinflammation and apoptosis in the hippocampus with significant losses of synaptic proteins when compared to the control. The expression and activity of cytokine-responsive indoleamine 2,3-dioxygenase (IDO-1), a catabolic enzyme of serotonin and tryptophan, was significantly increased in the CORT-treated group with lowered levels of serotonin. Besides, CORT markedly reduced dendritic length and spine density. Remarkably, M30 administration neutralized the aberrant changes in the hippocampus and prevented the induction of depressive-like behavior induced by CORT. Our results suggest that M30 is neuroprotective against CORT-induced depression targeting elevated MAO activities that cause oxidative stress and neuroinflammation, resulting in IDO-1 activation, serotonin deficiency and neurodegeneration.
Persistent Identifierhttp://hdl.handle.net/10722/242930
ISSN
2020 Impact Factor: 3.24
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLAM, CS-
dc.contributor.authorTipoe, GL-
dc.contributor.authorWong, KC-
dc.contributor.authorYoudim, MBH-
dc.contributor.authorFung, ML-
dc.date.accessioned2017-08-25T02:47:27Z-
dc.date.available2017-08-25T02:47:27Z-
dc.date.issued2016-
dc.identifier.citationPLoS One, 2016, v. 11 n. 11, p. e0166966:1-23-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/242930-
dc.description.abstractMonoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT). Sprague-Dawley rats were given CORT subcutaneous injections with or without concomitant M30 administration for two weeks. CORT-treated rats exhibited depressive-like behavior with significant elevated levels of MAO activities, serotonin turnover, oxidative stress, neuroinflammation and apoptosis in the hippocampus with significant losses of synaptic proteins when compared to the control. The expression and activity of cytokine-responsive indoleamine 2,3-dioxygenase (IDO-1), a catabolic enzyme of serotonin and tryptophan, was significantly increased in the CORT-treated group with lowered levels of serotonin. Besides, CORT markedly reduced dendritic length and spine density. Remarkably, M30 administration neutralized the aberrant changes in the hippocampus and prevented the induction of depressive-like behavior induced by CORT. Our results suggest that M30 is neuroprotective against CORT-induced depression targeting elevated MAO activities that cause oxidative stress and neuroinflammation, resulting in IDO-1 activation, serotonin deficiency and neurodegeneration.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS ONE-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleM30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus-
dc.typeArticle-
dc.identifier.emailTipoe, GL: tgeorge@hku.hk-
dc.identifier.emailWong, KC: kcwong47@hku.hk-
dc.identifier.emailFung, ML: fungml@hku.hk-
dc.identifier.authorityTipoe, GL=rp00371-
dc.identifier.authorityFung, ML=rp00433-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0166966-
dc.identifier.scopuseid_2-s2.0-84995955708-
dc.identifier.hkuros274263-
dc.identifier.volume11-
dc.identifier.issue11-
dc.identifier.spagee0166966:1-
dc.identifier.epage23-
dc.identifier.isiWOS:000388846400048-
dc.publisher.placeUnited States-
dc.identifier.issnl1932-6203-

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