| Texto completo | |
| Autor(es): |
Ikebara, Juliane Midori
;
Takada, Silvia Honda
;
Cardoso, Debora Sterzeck
;
Moralles Dias, Natalia Myuki
;
Vicente de Campos, Beatriz Crossiol
;
Sanches Bretherick, Talitha Amanda
;
Vilar Higa, Guilherme Shigueto
;
Ayres Ferraz, Mariana Sacrini
;
Kihara, Alexandre Hiroaki
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PLoS One; v. 12, n. 1 JAN 10 2017. |
| Citações Web of Science: | 3 |
| Resumo | |
Anoxia is one of the most prevalent causes of neonatal morbidity and mortality, especially in preterm neonates, constituting an important public health problem due to permanent neurological sequelae observed in patients. Oxygen deprivation triggers a series of simultaneous cascades, culminating in cell death mainly located in more vulnerable metabolic brain regions, such as the hippocampus. In the process of cell death by oxygen deprivation, cytosolic calcium plays crucial roles. Intracellular inositol 1,4,5-trisphosphate receptors (IP3Rs) are important regulators of cytosolic calcium levels, although the role of these receptors in neonatal anoxia is completely unknown. This study focused on the functional role of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in rat hippocampus after neonatal anoxia. Quantitative real-time PCR revealed a decrease of IP3R1 gene expression 24 hours after neonatal anoxia. We detected that IP3R1 accumulates specially in CA1, and this spatial pattern did not change after neonatal anoxia. Interestingly, we observed that anoxia triggers translocation of IP3R1 to nucleus in hippocampal cells. We were able to observe that anoxia changes distribution of IP3R1 immunofluorescence signals, as revealed by cluster size analysis. We next examined the role of IP3R1 in the neuronal cell loss triggered by neonatal anoxia. Intrahippocampal injection of non-specific IP3R1 blocker 2-APB clearly reduced the number of Fluoro-Jade C and Tunel positive cells, revealing that activation of IP3R1 increases cell death after neonatal anoxia. Finally, we aimed to disclose mechanistics of IP3R1 in cell death. We were able to determine that blockade of IP3R1 did not reduced the distribution and pixel density of activated caspase 3-positive cells, indicating that the participation of IP3R1 in neuronal cell loss is not related to classical caspase-mediated apoptosis. In summary, this study may contribute to new perspectives in the investigation of neurode-generative mechanisms triggered by oxygen deprivation. (AU) | |
| Processo FAPESP: | 14/15018-5 - Estudo do papel dos receptores intracelulares de cálcio inositol 1,4,5-trifosfato (IP3) no hipocampo de ratos após anóxia neonatal |
| Beneficiário: | Juliane Midori Ikebara |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 14/16711-6 - Relação entre acoplamento celular e microRNAs no desenvolvimento, adaptação e degeneração do sistema nervoso |
| Beneficiário: | Alexandre Hiroaki Kihara |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 15/17044-6 - O papel da junção comunicante neuronal na atividade espontânea hipocampal durante o desenvolvimeto |
| Beneficiário: | Guilherme Shigueto Vilar Higa |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |
| Processo FAPESP: | 15/19699-0 - Efeitos da administração intrahipocampal de 2-APB na memória espacial e na ansiedade de ratos submetidos à anóxia neonatal |
| Beneficiário: | Talitha Amanda Sanches Bretherick |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 15/19657-5 - Envolvimento do toll-like receptor tipo 4 (TLR4) na lesão hipocampal de camundongos submetidos à anóxia neonatal |
| Beneficiário: | Beatriz Crossiol Vicente de Campos |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 14/17434-6 - Análise da distribuição de VDAC-1 no hipocampo de ratos após anóxia neonatal |
| Beneficiário: | Débora Sterzeck Cardoso |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |