Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

Detalhes bibliográficos
Autor(a) principal: Cline, Brandon H.
Data de Publicação: 2015
Outros Autores: Costa-Nunes, Joao P., Cespuglio, Raymond, Markova, Natalyia, Santos, Ana I., Bukhman, Yury V., Kubatiev, Aslan, Steinbusch, Harry W.M., Lesch, Klaus Peter, Strekalova, Tatyana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/137317
Resumo: Publisher Copyright: © 2015 Cline, Costa-Nunes, Cespuglio, Markova, Santos, Bukhman, Kubatiev, Steinbusch, Lesch and Strekalova.
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spelling Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depressionAgingChronic stressDicholine succinateHippocampal plasticityInsulin receptorNMDA receptor subunits NR2A and NR2BPhosphorylated glycogen synthase kinase-3beta (pGSK-3beta)Sleep EEGNeuropsychology and Physiological PsychologyCognitive NeuroscienceBehavioral NeurosciencePublisher Copyright: © 2015 Cline, Costa-Nunes, Cespuglio, Markova, Santos, Bukhman, Kubatiev, Steinbusch, Lesch and Strekalova.Central insulin receptor-mediated signaling is attracting the growing attention of researchers because of rapidly accumulating evidence implicating it in the mechanisms of plasticity, stress response, and neuropsychiatric disorders including depression. Dicholine succinate (DS), a mitochondrial complex II substrate, was shown to enhance insulin-receptor mediated signaling in neurons and is regarded as a sensitizer of the neuronal insulin receptor. Compounds enhancing neuronal insulin receptor-mediated transmission exert an antidepressant-like effect in several pre-clinical paradigms of depression; similarly, such properties for DS were found with a stress-induced anhedonia model. Here, we additionally studied the effects of DS on several variables which were ameliorated by other insulin receptor sensitizers in mice. Pre-treatment with DS of chronically stressed C57BL6 mice rescued normal contextual fear conditioning, hippocampal gene expression of NMDA receptor subunit NR2A, the NR2A/NR2B ratio and increased REM sleep rebound after acute predation. In 18-month-old C57BL6 mice, a model of elderly depression, DS restored normal sucrose preference and activated the expression of neural plasticity factors in the hippocampus as shown by Illumina microarray. Finally, young naïve DS-treated C57BL6 mice had reduced depressive- and anxiety-like behaviors and, similarly to imipramine-treated mice, preserved hippocampal levels of the phosphorylated (inactive) form of GSK3 beta that was lowered by forced swimming in pharmacologically naïve animals. Thus, DS can ameliorate behavioral and molecular outcomes under a variety of stress- and depression-related conditions. This further highlights neuronal insulin signaling as a new factor of pathogenesis and a potential pharmacotherapy of affective pathologies.Instituto de Higiene e Medicina Tropical (IHMT)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Malária e outras Doenças Tropicais (CMDT)RUNCline, Brandon H.Costa-Nunes, Joao P.Cespuglio, RaymondMarkova, NatalyiaSantos, Ana I.Bukhman, Yury V.Kubatiev, AslanSteinbusch, Harry W.M.Lesch, Klaus PeterStrekalova, Tatyana2022-05-02T22:43:09Z2015-02-262015-02-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/137317eng1662-5153PURE: 43625603https://doi.org/10.3389/fnbeh.2015.00037info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:14:53Zoai:run.unl.pt:10362/137317Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:48:49.362533Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
title Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
spellingShingle Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
Cline, Brandon H.
Aging
Chronic stress
Dicholine succinate
Hippocampal plasticity
Insulin receptor
NMDA receptor subunits NR2A and NR2B
Phosphorylated glycogen synthase kinase-3beta (pGSK-3beta)
Sleep EEG
Neuropsychology and Physiological Psychology
Cognitive Neuroscience
Behavioral Neuroscience
title_short Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
title_full Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
title_fullStr Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
title_full_unstemmed Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
title_sort Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression
author Cline, Brandon H.
author_facet Cline, Brandon H.
Costa-Nunes, Joao P.
Cespuglio, Raymond
Markova, Natalyia
Santos, Ana I.
Bukhman, Yury V.
Kubatiev, Aslan
Steinbusch, Harry W.M.
Lesch, Klaus Peter
Strekalova, Tatyana
author_role author
author2 Costa-Nunes, Joao P.
Cespuglio, Raymond
Markova, Natalyia
Santos, Ana I.
Bukhman, Yury V.
Kubatiev, Aslan
Steinbusch, Harry W.M.
Lesch, Klaus Peter
Strekalova, Tatyana
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Higiene e Medicina Tropical (IHMT)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Malária e outras Doenças Tropicais (CMDT)
RUN
dc.contributor.author.fl_str_mv Cline, Brandon H.
Costa-Nunes, Joao P.
Cespuglio, Raymond
Markova, Natalyia
Santos, Ana I.
Bukhman, Yury V.
Kubatiev, Aslan
Steinbusch, Harry W.M.
Lesch, Klaus Peter
Strekalova, Tatyana
dc.subject.por.fl_str_mv Aging
Chronic stress
Dicholine succinate
Hippocampal plasticity
Insulin receptor
NMDA receptor subunits NR2A and NR2B
Phosphorylated glycogen synthase kinase-3beta (pGSK-3beta)
Sleep EEG
Neuropsychology and Physiological Psychology
Cognitive Neuroscience
Behavioral Neuroscience
topic Aging
Chronic stress
Dicholine succinate
Hippocampal plasticity
Insulin receptor
NMDA receptor subunits NR2A and NR2B
Phosphorylated glycogen synthase kinase-3beta (pGSK-3beta)
Sleep EEG
Neuropsychology and Physiological Psychology
Cognitive Neuroscience
Behavioral Neuroscience
description Publisher Copyright: © 2015 Cline, Costa-Nunes, Cespuglio, Markova, Santos, Bukhman, Kubatiev, Steinbusch, Lesch and Strekalova.
publishDate 2015
dc.date.none.fl_str_mv 2015-02-26
2015-02-26T00:00:00Z
2022-05-02T22:43:09Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/137317
url http://hdl.handle.net/10362/137317
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1662-5153
PURE: 43625603
https://doi.org/10.3389/fnbeh.2015.00037
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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