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Artículo

Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat

Benitez, Sergio GonzaloIcon ; Castro Zapata, Analia ElizabethIcon ; Patterson, Sean IngramIcon ; Muñoz, Estela MarisIcon ; Seltzer, Alicia MabelIcon
Fecha de publicación: 07/2014
Editorial: Public Library of Science
Revista: Plos One
ISSN: 1932-6203
Idioma: Inglés
Tipo de recurso: Artículo publicado

Resumen

In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc). Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67) and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C) rats and rats submitted to Pc, 5 hypoxia-ischemia (L) and a combination of both treatments (PcL). We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insult - showing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborization - were not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ~110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult, the former are protected by a preconditioning hypoxia while the latter are not.
Palabras clave: Cerebellum , Hypoxic Preconditioning , Neonatal Hypoxia-Ischemia , Gabaergic Neurons , Glutamatergic Neurons , Neurod1 , Gad67
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)
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URI: http://hdl.handle.net/11336/32356
URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102512/pdf/pone.0102056.pdf
DOI: http://dx.doi.org/10.1371/journal.pone.0102056. eCollection 2014.
URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102056
Colecciones
Articulos(IHEM) [270]
Articulos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Citación
Benitez, Sergio Gonzalo; Castro Zapata, Analia Elizabeth; Patterson, Sean Ingram; Muñoz, Estela Maris; Seltzer, Alicia Mabel; Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat; Public Library of Science; Plos One; 9; 7; 7-2014; 1-13; e102056
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