| Full text | |
| Author(s): |
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
Total Authors: 9
|
| Document type: | Journal article |
| Source: | PLoS One; v. 12, n. 1 JAN 10 2017. |
| Web of Science Citations: | 3 |
| Abstract | |
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) | |
| FAPESP's process: | 14/15018-5 - Study of the role of intracellular calcium receptors inositol 1,4,5-triphosphate (IP3) in the hippocampus of rats after neonatal anoxia |
| Grantee: | Juliane Midori Ikebara |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 14/16711-6 - MicroRNAs and cell coupling interplay in the development, adaptation and degeneration of the nervous system |
| Grantee: | Alexandre Hiroaki Kihara |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/17044-6 - The role of neuronal gap junctions in the hippocampal spontaneous activity during development |
| Grantee: | Guilherme Shigueto Vilar Higa |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 15/19699-0 - Efeitos da administração intrahipocampal de 2-APB na memória espacial e na ansiedade de ratos submetidos à anóxia neonatal |
| Grantee: | Talitha Amanda Sanches Bretherick |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 15/19657-5 - Involviment of toll-like receptor type 4 (TLR4) in a hippocampal injury in mouse subject in anoxia neonatal |
| Grantee: | Beatriz Crossiol Vicente de Campos |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 14/17434-6 - Analysis of the distribution of VDAC-1 in rat hippocampus following neonatal anoxia |
| Grantee: | Débora Sterzeck Cardoso |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |