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Título: | Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function |
Autor: | Fernandez-Fernandez, Seila CSIC; Bobo-Jimenez, Veronica CSIC; Requejo-Aguilar, Raquel CSIC; Gonzalez-Fernandez, Silvia; Resch-Beusher, Monica CSIC; Carabias-Carrasco, Mónica CSIC; Ros, Joaquim; Almeida, Angeles CSIC ORCID; Bolaños, Juan P. CSIC ORCID | Palabras clave: | Neurons Glutamate-cysteine ligase GlutathioneIn vivo knockdown Dendrite disruption Memory impairment |
Fecha de publicación: | oct-2018 | Editor: | Elsevier | Citación: | Redox Biology 19: 52-61 (2018) | Resumen: | Loss of brain glutathione has been associated with cognitive decline and neuronal death during aging and neurodegenerative diseases. However, whether decreased glutathione precedes or follows neuronal dysfunction has not been unambiguously elucidated. Previous attempts to address this issue were approached by fully eliminating glutathione, a strategy causing abrupt lethality or premature neuronal death that led to multiple interpretations. To overcome this drawback, here we aimed to moderately decrease glutathione content by genetically knocking down the rate-limiting enzyme of glutathione biosynthesis in mouse neurons in vivo. Biochemical and morphological analyses of the brain revealed a modest glutathione decrease and redox stress throughout the hippocampus, although neuronal dendrite disruption and glial activation was confined to the hippocampal CA1 layer. Furthermore, the behavioral characterization exhibited signs consistent with cognitive impairment. These results indicate that the hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function. | Versión del editor: | https://doi.org/10.1016/j.redox.2018.08.003 | URI: | http://hdl.handle.net/10261/183267 | DOI: | 10.1016/j.redox.2018.08.003 | ISSN: | 2213-2317 | E-ISSN: | 2213-2317 |
Aparece en las colecciones: | (IBFG) Artículos |
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Hippocampal neurons_FernandezFernandez.pdf | 2 MB | Adobe PDF | Visualizar/Abrir |
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