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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

NEONATAL ANOXIA IN RATS: HIPPOCAMPAL CELLULAR AND SUBCELLULAR CHANGES RELATED TO CELL DEATH AND SPATIAL MEMORY

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Autor(es):
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Takada, S. H. [1, 2] ; Dos Santos Haemmerle, C. A. [1] ; Motta-Teixeira, L. C. [3] ; Machado-Nils, A. V. [3] ; Lee, V. Y. [1] ; Takase, L. F. [4] ; Cruz-Rizzolo, R. J. [5] ; Kihara, A. H. [2] ; Xavier, G. F. [3] ; Watanabe, I. -S. [1] ; Nogueira, M. I. [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Anat, BR-05508 Sao Paulo - Brazil
[2] Univ Fed ABC, Ctr Matemat Computacao & Cognicao, Nucleo Cognicao & Sistemas Complexos, Santo Andre - Brazil
[3] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, Sao Paulo - Brazil
[4] Univ Fed Sao Carlos, Ctr Ciencias Biol & Saude, Dept Morfol & Patol, BR-13560 Sao Carlos, SP - Brazil
[5] Univ Estadual Paulista, Dept Ciencias Basicas, Aracatuba - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Neuroscience; v. 284, p. 247-259, JAN 22 2015.
Citações Web of Science: 16
Resumo

Neonatal anoxia in rodents has been used to understand brain changes and cognitive dysfunction following asphyxia. This study investigated the time-course of cellular and subcellular changes and hippocampal cell death in a non-invasive model of anoxia in neonatal rats, using Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL) to reveal DNA fragmentation, Fluoro-Jade(R) B (FJB) to show degenerating neurons, cleaved caspase-3 immunohistochemistry (IHC) to detect cells undergoing apoptosis, and transmission electron microscopy (TEM) to reveal fine ultrastructural changes related to cell death. Anoxia was induced by exposing postnatal day 1 (P1) pups to a flow of 100% gaseous nitrogen for 25 min in a chamber maintained at 37 degrees C. Control rats were similarly exposed to this chamber but with air flow instead of nitrogen. Brain changes following anoxia were evaluated at postnatal days 2, 14, 21 and 60 (P2, P14, P21 and P60). In addition, spatial reference memory following anoxia and control treatments was evaluated in the Morris water maze, starting at P60. Compared to their respective controls, P2 anoxic rats exhibited (1) higher TUNEL labeling in cornus ammonis (CA) 1 and the dentate gyrus (DG), (2) higher FJB-positive cells in the CA2-3, and (3) somato-dendritic swelling, mitochondrial injury and chromatin condensation in irregular bodies, as well as other subcellular features indicating apoptosis, necrosis, autophagy and excitotoxicity in the CA1, CA2-3 and DG, as revealed by TEM. At P14, P21 and P60, both groups showed small numbers of TUNEL-positive and FJB-positive cells. Stereological analysis at P2, P14, P21 and P60 revealed a lack of significant differences in cleaved caspase-3 IHC between anoxic and control subjects. These results suggest that the type of hippocampal cell death following neonatal anoxia is likely independent of caspase-3 activation. Neonatal anoxia induced deficits in acquisition and performance of spatial reference memory in the Morris water maze task. Compared to control subjects, anoxic animals exhibited increased latencies and path lengths to reach the platform, as well as decreased searching specifically for the platform location. In contrast, no significant differences were observed for swimming speeds and frequency within the target quadrant. Together, these behavioral results indicate that the poorer performance by anoxic subjects is related to spatial memory deficits and not to sensory or motor deficits. Therefore, this model of neonatal anoxia in rats induces hippocampal changes that result in cell losses and impaired hippocampal function, and these changes are likely related to spatial memory deficits in adulthood. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

Processo FAPESP: 11/19747-3 - Organização e ultra-estrutura das células imunorreativas a 5-bromo-2'-deoxiuridina (BrdU) do nicho neurogênico do ventrículo lateral, em ratos (Rattus norvegicus) Long-Evans
Beneficiário:Maria Inês Nogueira
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/51557-0 - Estudo da organizacao e maturacao neuronais no hipocampo de ratos apos anoxia neonatal
Beneficiário:Silvia Honda Takada
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 10/01488-9 - Estudo da organização e dinâmica neuronal: morte neuronal e neurogênese no encéfalo de ratos após anóxia neonatal
Beneficiário:Maria Inês Nogueira
Modalidade de apoio: Auxílio à Pesquisa - Regular