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


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.

SUBMITTER: Fernandez-Fernandez S 

PROVIDER: S-EPMC6092450 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Fernandez-Fernandez Seila S   Bobo-Jimenez Veronica V   Requejo-Aguilar Raquel R   Gonzalez-Fernandez Silvia S   Resch Monica M   Carabias-Carrasco Monica M   Ros Joaquim J   Almeida Angeles A   Bolaños Juan P JP  

Redox biology 20180807


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 d  ...[more]

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