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

Fernandez-Fernandez, Seila; Bobo-Jimenez, Veronica; Requejo-Aguilar, Raquel; Gonzalez-Fernandez, Silvia; Resch, Monica; Carabias-Carrascoa, Monica; Ros Salvador, Joaquim; Almeida, Angeles; Bolaños, Juan P.

doi:https://doi.org/10.1016/j.redox.2018.08.003

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Issue date

2018

Author

Fernandez-Fernandez, Seila

Bobo-Jimenez, Veronica

Requejo-Aguilar, Raquel

Gonzalez-Fernandez, Silvia

Resch, Monica

Carabias-Carrascoa, Monica

Ros Salvador, Joaquim

Almeida, Angeles

Bolaños, Juan P.

Suggested citation

Fernandez-Fernandez, Seila; Bobo-Jimenez, Veronica; Requejo-Aguilar, Raquel; Gonzalez-Fernandez, Silvia; Resch, Monica; Carabias-Carrascoa, Monica; ... Bolaños, Juan P.. (2018) . Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function. Redox Biology, 2018, vol. 19, p. 52-61. https://doi.org/10.1016/j.redox.2018.08.003.

Abstract

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.

URI

http://hdl.handle.net/10459.1/64860

DOI

https://doi.org/10.1016/j.redox.2018.08.003

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Redox Biology, 2018, vol. 19, p. 52-61

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Except where otherwise noted, this item's license is described as cc-by-nc-nd (c) Seila Fernandez-Fernandez et al., 2018