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Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function

AuthorsFernandez-Fernandez, Seila CSIC; Bobo-Jimenez, Veronica CSIC; Requejo-Aguilar, Raquel; Gonzalez-Fernandez, Silvia; Resch-Beusher, Monica; Carabias-Carrasco, Mónica; Ros, Joaquim; Almeida, Angeles CSIC ORCID; Bolaños, Juan P. CSIC ORCID
Glutamate-cysteine ligase
GlutathioneIn vivo knockdown
Dendrite disruption
Memory impairment
Issue DateOct-2018
CitationRedox Biology 19: 52-61 (2018)
AbstractLoss 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.
Publisher version (URL)https://doi.org/10.1016/j.redox.2018.08.003
Appears in Collections:(IBFG) Artículos
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