Perisynaptic astrocytes as a potential target for novel antidepressant drugs
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/218524 |
Resumo: | Emerging evidence suggests that dysfunctions in glutamatergic signaling are associated with the pathophysiology of depression. Several molecules that act on glutamate binding sites, so-called glutamatergic modulators, are rapid-acting antidepressants that stimulate synaptogenesis. Their antidepressant response involves the elevation of both extracellular glutamate and brain-derived neurotrophic factor (BDNF) levels, as well as the postsynaptic activation of the mammalian target of rapamycin complex 1. The mechanisms involved in the antidepressant outcomes of glutamatergic modulators, including ketamine, suggest that astrocytes must be considered a cellular target for developing rapid-acting antidepressants. It is well known that extracellular glutamate levels and glutamate intrasynaptic time-coursing are maintained by perisynaptic astrocytes, where inwardly rectifying potassium channels 4.1 (Kir4.1 channels) regulate both potassium and glutamate uptake. In addition, ketamine reduces membrane expression of Kir4.1 channels, which raises extracellular potassium and glutamate levels, increasing postsynaptic neural activities. Furthermore, inhibition of Kir4.1 channels stimulates BDNF expression in astrocytes, which may enhance synaptic connectivity. In this review, we discuss glutamatergic modulators’ actions in regulating extracellular glutamate and BDNF levels, and reinforce the importance of perisynaptic astrocytes for the development of novel antidepressant drugs. |
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Frizzo, Marcos Emilio dos SantosOhno, Yukihiro2021-03-10T04:21:08Z20211347-8613http://hdl.handle.net/10183/218524001122399Emerging evidence suggests that dysfunctions in glutamatergic signaling are associated with the pathophysiology of depression. Several molecules that act on glutamate binding sites, so-called glutamatergic modulators, are rapid-acting antidepressants that stimulate synaptogenesis. Their antidepressant response involves the elevation of both extracellular glutamate and brain-derived neurotrophic factor (BDNF) levels, as well as the postsynaptic activation of the mammalian target of rapamycin complex 1. The mechanisms involved in the antidepressant outcomes of glutamatergic modulators, including ketamine, suggest that astrocytes must be considered a cellular target for developing rapid-acting antidepressants. It is well known that extracellular glutamate levels and glutamate intrasynaptic time-coursing are maintained by perisynaptic astrocytes, where inwardly rectifying potassium channels 4.1 (Kir4.1 channels) regulate both potassium and glutamate uptake. In addition, ketamine reduces membrane expression of Kir4.1 channels, which raises extracellular potassium and glutamate levels, increasing postsynaptic neural activities. Furthermore, inhibition of Kir4.1 channels stimulates BDNF expression in astrocytes, which may enhance synaptic connectivity. In this review, we discuss glutamatergic modulators’ actions in regulating extracellular glutamate and BDNF levels, and reinforce the importance of perisynaptic astrocytes for the development of novel antidepressant drugs.application/pdfengJournal of pharmacological sciences. Kyoto. Vol. 145, no. 1 (Jan. 2021), p. 60-68DepressãoAntidepressivosÁcido glutâmicoAstrócitosFator neurotrófico derivado do encéfaloDepressionGlutamatergic modulatorKir4.1 channelsBDNFKetaminePerisynaptic astrocytes as a potential target for novel antidepressant drugsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001122399.pdf.txt001122399.pdf.txtExtracted Texttext/plain64485http://www.lume.ufrgs.br/bitstream/10183/218524/2/001122399.pdf.txt89ed2113a726b4db8a7498036d22da83MD52ORIGINAL001122399.pdfTexto completo (inglês)application/pdf978293http://www.lume.ufrgs.br/bitstream/10183/218524/1/001122399.pdfbe7e402426dc4d8534c6f5f66458cbfcMD5110183/2185242021-05-07 04:37:14.747039oai:www.lume.ufrgs.br:10183/218524Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-05-07T07:37:14Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs |
title |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs |
spellingShingle |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs Frizzo, Marcos Emilio dos Santos Depressão Antidepressivos Ácido glutâmico Astrócitos Fator neurotrófico derivado do encéfalo Depression Glutamatergic modulator Kir4.1 channels BDNF Ketamine |
title_short |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs |
title_full |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs |
title_fullStr |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs |
title_full_unstemmed |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs |
title_sort |
Perisynaptic astrocytes as a potential target for novel antidepressant drugs |
author |
Frizzo, Marcos Emilio dos Santos |
author_facet |
Frizzo, Marcos Emilio dos Santos Ohno, Yukihiro |
author_role |
author |
author2 |
Ohno, Yukihiro |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Frizzo, Marcos Emilio dos Santos Ohno, Yukihiro |
dc.subject.por.fl_str_mv |
Depressão Antidepressivos Ácido glutâmico Astrócitos Fator neurotrófico derivado do encéfalo |
topic |
Depressão Antidepressivos Ácido glutâmico Astrócitos Fator neurotrófico derivado do encéfalo Depression Glutamatergic modulator Kir4.1 channels BDNF Ketamine |
dc.subject.eng.fl_str_mv |
Depression Glutamatergic modulator Kir4.1 channels BDNF Ketamine |
description |
Emerging evidence suggests that dysfunctions in glutamatergic signaling are associated with the pathophysiology of depression. Several molecules that act on glutamate binding sites, so-called glutamatergic modulators, are rapid-acting antidepressants that stimulate synaptogenesis. Their antidepressant response involves the elevation of both extracellular glutamate and brain-derived neurotrophic factor (BDNF) levels, as well as the postsynaptic activation of the mammalian target of rapamycin complex 1. The mechanisms involved in the antidepressant outcomes of glutamatergic modulators, including ketamine, suggest that astrocytes must be considered a cellular target for developing rapid-acting antidepressants. It is well known that extracellular glutamate levels and glutamate intrasynaptic time-coursing are maintained by perisynaptic astrocytes, where inwardly rectifying potassium channels 4.1 (Kir4.1 channels) regulate both potassium and glutamate uptake. In addition, ketamine reduces membrane expression of Kir4.1 channels, which raises extracellular potassium and glutamate levels, increasing postsynaptic neural activities. Furthermore, inhibition of Kir4.1 channels stimulates BDNF expression in astrocytes, which may enhance synaptic connectivity. In this review, we discuss glutamatergic modulators’ actions in regulating extracellular glutamate and BDNF levels, and reinforce the importance of perisynaptic astrocytes for the development of novel antidepressant drugs. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-03-10T04:21:08Z |
dc.date.issued.fl_str_mv |
2021 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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http://hdl.handle.net/10183/218524 |
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1347-8613 |
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001122399 |
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eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Journal of pharmacological sciences. Kyoto. Vol. 145, no. 1 (Jan. 2021), p. 60-68 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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