Thyroid hormone treated astrocytes induce maturation of cerebral cortical neurons through modulation of proteoglycan levels

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dc.contributor.authorDezonne, Romulo S.
dc.contributor.authorStipursky, Joice
dc.contributor.authorAraujo, Ana P. B.
dc.contributor.authorNones, Jader
dc.contributor.authorPavao, Mauro S. G.
dc.contributor.authorPorcionatto, Marimelia [UNIFESP]
dc.contributor.authorGomes, Flavia C. A.
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:32:07Z
dc.date.available2016-01-24T14:32:07Z
dc.date.issued2013-08-12
dc.description.abstractProper brain neuronal circuitry formation and synapse development is dependent on specific cues, either genetic or epigenetic, provided by the surrounding neural environment. Within the sesignals, thyroid hormones (T3 and T4) play crucial role in several steps of brain morphogenesis including proliferation of progenitor cells, neuronal differentiation, maturation, migration, and synapse formation. the lack of thyroid hormones during childhood is associated with several impair neuronal connections, cognitive deficits, and mental disorders. Many of the thyroid hormones effects are mediated by astrocytes, although the mechanisms underlying these events are still unknown. in this work, we investigated the effect of 3,5,3'-triiodothyronine-treated (T3-treated) astrocytes on cerebral cortex neuronal differentiation. Culture of neural progenitors from embryonic cerebral cortex mice onto T3-treated astrocyte monolayers yielded an increment in neuronal population, followed by enhancement of neuronal maturation, arborization and neurite outgrowth. in addition, real time PCR assays revealed an increase in the levels of the heparan sulfate proteoglycans, Glypican 1(GPC-1) and Syndecans 3 e 4 (SDC-3 e SDC-4), followed by a decrease in the levels of the chondroitin sulfate proteoglycan, Versican. Disruption of glycosaminoglycan chains by chondroitinase AC or heparanase III completely abolished the effects of T3-treated astrocytes on neuronal morphogenesis. Our work provides evidence that astrocytes are key mediators of T3 actions on cerebral cortex neuronal development and identified potential molecules and pathways involved in neurite extension; which might eventually contribute to a better understanding of axonal regeneration, synapse formation, and neuronal circuitry recover.en
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21949590 Rio de Janeiro, RJ, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Bioquim Med, BR-21949590 Rio de Janeiro, RJ, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, BR-21949590 Rio de Janeiro, RJ, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.description.sponsorshipConselho Nacional para o Desenvolvimento Cientifico e Tecnologico
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent12
dc.identifierhttp://dx.doi.org/10.3389/fncel.2013.00125
dc.identifier.citationFrontiers in Cellular Neuroscience. Lausanne: Frontiers Research Foundation, v. 7, 12 p., 2013.
dc.identifier.doi10.3389/fncel.2013.00125
dc.identifier.fileWOS000323414500001.pdf
dc.identifier.issn1662-5102
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/36646
dc.identifier.wosWOS:000323414500001
dc.language.isoeng
dc.publisherFrontiers Research Foundation
dc.relation.ispartofFrontiers in Cellular Neuroscience
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectastrocyteen
dc.subjectthyroid hormonesen
dc.subjectneurite outgrowthen
dc.subjectextracellular matrixen
dc.subjectbrain morphogenesisen
dc.titleThyroid hormone treated astrocytes induce maturation of cerebral cortical neurons through modulation of proteoglycan levelsen
dc.typeinfo:eu-repo/semantics/article
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