Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function
Year: 2018
Type: article
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.
Source: Redox Biology
Institutions: Universidad de Salamanca, Instituto de Biología Funcional y Genómica, Instituto de Investigación Biomédica de Salamanca, Instituto Maimónides de Investigación Biomédica de Córdoba, University of Córdoba, Universitat de Lleida, Instituto de Investigación Biomédica de Lleida, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,310
Funders: Fundación Ramón Areces, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, European Commission, Ministerio de Economía y Competitividad, Universitat de Lleida, Universidad de Salamanca, Junta de Castilla y León, Horizon 2020 Framework Programme, Instituto de Salud Carlos III, European Regional Development Fund, European Social Fund
Awards: G1075078508, G1323321317, G1349139012, G207230964, G2880616440, Developing new therapies for Batten disease, G4347308769, G4748589373, G4937468798, PROMOTING ACTIVE AGEING: FUNCTIONAL NANOSTRUCTURES FOR ALZHEIMER’S DISEASE AT ULTRA-EARLY STAGES., Función de la E3 ubiquitina ligasa APC/C-Cdh1 en la reparación cerebral y pronóstico funcional tras el ictus, G7507679353, G8525137491, G8824911526
OpenAlex ID: W2886346355