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Doctoral Thesis
DOI
Document
Author
Full name
Érica de Almeida Duque
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Munhoz, Carolina Demarchi (President)
Carrettiero, Daniel Carneiro
Fernandes, Pedro Augusto Carlos Magno
Lotufo, Leticia Veras Costa
Steiner, Alexandre Alarcon
Title in Portuguese
Efeitos dos glicocorticoides nas interações celulares de astrócitos, microglia e neurônios durante inflamação induzida por LPS em modelo in vitro.
Keywords in Portuguese
Astrócitos
Córtex cerebral
Glicocorticoides
Microglia
NFKB
Abstract in Portuguese
O bom funcionamento da tríade neurônio-microglia-astrócito é fundamental para a manutenção das funções no sistema nervoso central (SNC), uma vez que processos neurodegenerativos e de envelhecimento podem estar relacionados a uma interação celular defeituosa entre os neurônios e as células da glia. A ativação e o recrutamento das células da glia são processos complexos e exigem uma intercomunicação bem organizada dos neurônios e as células da glia, bem como das células da glia. Apesar do bem estabelecido efeito anti-inflamatório dos glicocorticoides (GCs), tem sido demonstrado que, no SNC, níveis aumentados desse hormônio podem potencializar alguns aspectos da resposta inflamatória, por exemplo, a ativação do fator de transcrição NFKB induzida por lipopolissacarídeo (LPS) e são cada vez maiores as evidências que apontam para a especificidade celular dessas ações. Este estudo tem como objetivo caracterizar os efeitos dos GCs nas interações celulares físicas e humorais entre astrócitos, microglia e neurônios na presença de um estímulo inflamatório agudo, o LPS, em modelos in vitro de culturas primárias derivadas do córtex cerebral de ratos neonatos. Verificamos que os GCs não são anti-inflamatórios, pois não diminuem a ativação do NFKB, e ainda potencializam a morte celular induzida pelo LPS em culturas mistas. Em astrócitos, nossos resultados sugerem que os GCs são pró-inflamatórios e essa ação parece depender das interações celulares e da presença de heterodímeros de GR/MR. A microglia participa da resposta dos astrócitos ao LPS em relação à localização nuclear do RELA.
Title in English
Glucocorticoids effects on LPS-induced inflammation in rat primary frontal cortex cultures.
Keywords in English
Astrocytes. Microglia
Cerebral Cortex
Glucocorticoids
Neuroinflammation
NFKB
Abstract in English
The proper functioning of the neuron-microglia-astrocyte triad is fundamental for the maintenance of central nervous system (CNS), since neurodegenerative and aging processes may be related to a "defective" cellular interaction between neurons and glia. Activation and recruitment of glial cells are complex processes and require well-organized intercommunication between neurons and glial cells as well as between glial cells. Despite the well-established anti-inflammatory effect of glucocorticoids (GCs), it has been shown that, in the CNS, increased levels of this hormone may potentiate some aspects of the inflammatory response, for example the activation of the lipopolysaccharide-induced NFKB transcription factor and the evidence pointing to the cellular specificity of these actions is increasing. This study aims to characterize the effects of GCs on physical and humoral cellular interactions between astrocytes, microglia, and neurons in the presence of an acute inflammatory stimulus, LPS, in in vitro primary cell cultures derived from the brain cortex of neonatal rats. We verified that GCs are not anti-inflammatory since they do not decrease the activation of NFKB and yet potentiate the LPS-induced cell death in mixed cultures. Astrocytes in mixed, neuron- and astrocyte-enriched cultures have different responses to LPS, as well as previous treatment with GCs, regarding the nuclear localization of RELA, an indication of its activation. Our results in this cell type suggest that GCs are proinflammatory and this action seems to depend on cell interactions and the presence of GR / MR heterodimers. Microglia participates in the response of astrocytes to LPS in relation to the nuclear localization of RELA.
 
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Release Date
2021-10-15
Publishing Date
2019-10-29
 
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