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Doctoral Thesis
DOI
10.11606/T.42.2011.tde-10022012-132908
Document
Author
Full name
Kelly Cristina Saito
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Hamassaki, Dania Emi (President)
Britto, Luiz Roberto Giorgetti de
Castrucci, Ana Maria de Lauro
Ventura, Dora Selma Fix
Yan, Chao Yun Irene
Title in Portuguese
Envolvimento de Rac1 na excitotoxicidade induzida por NMDA na retina de ratos.
Keywords in Portuguese
Glutamatos
Proteínas G
Ratos
Receptores de glutamato
Retina
Toxicidade em animal
Abstract in Portuguese
A ativação excessiva dos receptores NMDA tem sido descrita no disparo da morte neuronal que ocorre em doenças, como o glaucoma. É possível que a combinação de subunidades (NR2A-D) possa ativar vias de sinalização intracelulares que resultam na morte ou sobrevivência. Nosso objetivo foi investigar o envolvimento de subunidades NR2 e Rac1, membro da família Rho GTPase, na morte de neurônios da retina. A morte induzida por glutamato in vitro foi reduzida após a inibição de Rac1 e bloqueio de NR2B, mas não das subunidades NR2C/D. Resultados semelhantes foram obtidos in vivo após injeção intravítrea NMDA, e a detecção de Rac1 ativo, principalmente, nos processos de glia de Müller foi inibida pelo bloqueio NR2B. Além disso, a produção de TNF-α após a injeção de NMDA foi reduzida pelo bloqueio de NR2B e Rac1. Assim, nossos resultados sugerem que a excitotoxicidade via receptores NR2B/NMDA ativa Rac1 em células da glia de Müller, que por sua vez controla a produção de TNF-α possível responsável pela morte de células ganglionares da retina.
Title in English
Involvement of Rac1 in NMDA-induced excitotoxicity in the rat retina.
Keywords in English
Glutamate receptors
Glutamates
Protein G
Rats
Retina
Toxicity in animal
Abstract in English
Overactivation of NMDA receptors has been described to trigger neuronal death that occurs in diseases such as glaucoma. It is possible that the combination of subunits (NR2A-D) activate intracellular signaling pathways that result in death or survival. Our aim was to investigate the involvement of NR2 subunits and Rac1, a member of Rho GTPase family, in retinal neuronal death. Glutamate-induced neuronal death in vitro was reduced after Rac1 inhibition and by NR2B blocking, but not NR2C/D subunits. Similar results were obtained in vivo after NMDA intravitreous injection, although active Rac1 was mainly detected in Müller glia processes, and it was inhibited by NR2B blockade. In addition, TNF-α level after NMDA injection were reduced by NR2B blocking and Rac1. Thus, our results suggest that excitotoxicity via NR2B/NMDA receptors activate Rac1 in Müller glia cells, which in turn controls the TNF-α production that triggers retinal ganglion cell death.
 
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Release Date
2017-05-08
Publishing Date
2012-03-14
 
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