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

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2018Author
Fernandez-Fernandez, Seila
Bobo-Jimenez, Veronica
Requejo-Aguilar, Raquel
Gonzalez-Fernandez, Silvia
Resch, Monica
Carabias-Carrascoa, Monica
Almeida, Angeles
Bolaños, Juan P.
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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.
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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.
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Redox Biology, 2018, vol. 19, p. 52-61European research projects
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