Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function
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 app...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-10-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231718303926 |
| _version_ | 1819082746640728064 |
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| author | Seila Fernandez-Fernandez Veronica Bobo-Jimenez Raquel Requejo-Aguilar Silvia Gonzalez-Fernandez Monica Resch Monica Carabias-Carrasco Joaquim Ros Angeles Almeida Juan P. Bolaños |
| author_facet | Seila Fernandez-Fernandez Veronica Bobo-Jimenez Raquel Requejo-Aguilar Silvia Gonzalez-Fernandez Monica Resch Monica Carabias-Carrasco Joaquim Ros Angeles Almeida Juan P. Bolaños |
| author_sort | Seila Fernandez-Fernandez |
| collection | DOAJ |
| description | 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. Keywords: Neurons, Glutamate-cysteine ligase, Glutathione, In vivo knockdown, Dendrite disruption, Memory impairment |
| first_indexed | 2024-12-21T20:21:34Z |
| format | Article |
| id | doaj.art-1a2bfe24eb2e4c2aa575d43ec958f2d2 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-21T20:21:34Z |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-1a2bfe24eb2e4c2aa575d43ec958f2d22022-12-21T18:51:28ZengElsevierRedox Biology2213-23172018-10-01195261Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive functionSeila Fernandez-Fernandez0Veronica Bobo-Jimenez1Raquel Requejo-Aguilar2Silvia Gonzalez-Fernandez3Monica Resch4Monica Carabias-Carrasco5Joaquim Ros6Angeles Almeida7Juan P. Bolaños8Institute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, SpainInstitute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), Hospital Universitario de Salamanca, SpainInstitute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, Spain; Córdoba Maimónides Institute for Biomedical Research (IMIBIC), University of Cordoba, SpainInstitute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, SpainInstitute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, SpainInstitute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, SpainDepartamento de Ciències Mèdiques Bàsiques, IRBLleida, Universitat de Lleida, SpainInstitute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), Hospital Universitario de Salamanca, SpainInstitute of Functional Biology and Genomics (IBFG), Universidad de Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), Hospital Universitario de Salamanca, Spain; CIBERFES, Instituto de Salud Carlos, III, Madrid, Spain; Corresponding author at: Institute of Functional Biology and Genomics (IBFG), University of Salamanca-CSIC, C/Zacarías González, 2, 37007 Salamanca, Spain.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. Keywords: Neurons, Glutamate-cysteine ligase, Glutathione, In vivo knockdown, Dendrite disruption, Memory impairmenthttp://www.sciencedirect.com/science/article/pii/S2213231718303926 |
| spellingShingle | Seila Fernandez-Fernandez Veronica Bobo-Jimenez Raquel Requejo-Aguilar Silvia Gonzalez-Fernandez Monica Resch Monica Carabias-Carrasco Joaquim Ros Angeles Almeida Juan P. Bolaños Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function Redox Biology |
| title | Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function |
| title_full | Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function |
| title_fullStr | Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function |
| title_full_unstemmed | Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function |
| title_short | Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function |
| title_sort | hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function |
| url | http://www.sciencedirect.com/science/article/pii/S2213231718303926 |
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