β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical Neurons
β-Amyloid deposition and compromised energy metabolism both occur in vulnerable brain regions in Alzheimer's disease. It is not known whether β-amyloid is the cause of impairment of energy metabolism, nor whether impaired energy metabolism is specific to neurons. Our results, using primary neur...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2002-08-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996102905164 |
| _version_ | 1818414556324560896 |
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| author | C.S. Casley J.M. Land M.A. Sharpe J.B. Clark M.R. Duchen L. Canevari |
| author_facet | C.S. Casley J.M. Land M.A. Sharpe J.B. Clark M.R. Duchen L. Canevari |
| author_sort | C.S. Casley |
| collection | DOAJ |
| description | β-Amyloid deposition and compromised energy metabolism both occur in vulnerable brain regions in Alzheimer's disease. It is not known whether β-amyloid is the cause of impairment of energy metabolism, nor whether impaired energy metabolism is specific to neurons. Our results, using primary neuronal cultures, show that 24-h incubation with Aβ25–35 caused a generalized decrease in the specific activity of mitochondrial enzymes per milligram of cellular protein, induced mitochondrial swelling, and decreased total mitochondrial number. Incubation with Aβ25–35 decreased ATP concentration to 58% of control in neurons and 71% of control in astrocytes. Levels of reduced glutathione were also lowered by Aβ25–35 in both neurons (from 5.1 to 2.9 nmol/mg protein) and astrocytes (from 25.2 to 14.9 nmol/mg protein). We conclude that 24-h treatment with extracellular Aβ25–35 causes mitochondrial dysfunction in both astrocytes and neurons, the latter being more seriously affected. In astrocytes mitochondrial impairment was confined to complex I inhibition, whereas in neurons a generalized loss of mitochondria was seen. |
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| format | Article |
| id | doaj.art-6c821842d0814a658d080ae001f39fe0 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T11:20:58Z |
| publishDate | 2002-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-6c821842d0814a658d080ae001f39fe02022-12-21T23:03:46ZengElsevierNeurobiology of Disease1095-953X2002-08-01103258267β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical NeuronsC.S. Casley0J.M. Land1M.A. Sharpe2J.B. Clark3M.R. Duchen4L. Canevari5Division of Neurochemistry, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, United Kingdom; Department of Physiology, University College London, Gower St. London, WC1E 6BT, United Kingdom; Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United KingdomDivision of Neurochemistry, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, United Kingdom; Department of Physiology, University College London, Gower St. London, WC1E 6BT, United Kingdom; Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United KingdomDivision of Neurochemistry, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, United Kingdom; Department of Physiology, University College London, Gower St. London, WC1E 6BT, United Kingdom; Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United KingdomDivision of Neurochemistry, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, United Kingdom; Department of Physiology, University College London, Gower St. London, WC1E 6BT, United Kingdom; Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United KingdomDivision of Neurochemistry, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, United Kingdom; Department of Physiology, University College London, Gower St. London, WC1E 6BT, United Kingdom; Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United KingdomDivision of Neurochemistry, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, United Kingdom; Department of Physiology, University College London, Gower St. London, WC1E 6BT, United Kingdom; Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdomβ-Amyloid deposition and compromised energy metabolism both occur in vulnerable brain regions in Alzheimer's disease. It is not known whether β-amyloid is the cause of impairment of energy metabolism, nor whether impaired energy metabolism is specific to neurons. Our results, using primary neuronal cultures, show that 24-h incubation with Aβ25–35 caused a generalized decrease in the specific activity of mitochondrial enzymes per milligram of cellular protein, induced mitochondrial swelling, and decreased total mitochondrial number. Incubation with Aβ25–35 decreased ATP concentration to 58% of control in neurons and 71% of control in astrocytes. Levels of reduced glutathione were also lowered by Aβ25–35 in both neurons (from 5.1 to 2.9 nmol/mg protein) and astrocytes (from 25.2 to 14.9 nmol/mg protein). We conclude that 24-h treatment with extracellular Aβ25–35 causes mitochondrial dysfunction in both astrocytes and neurons, the latter being more seriously affected. In astrocytes mitochondrial impairment was confined to complex I inhibition, whereas in neurons a generalized loss of mitochondria was seen.http://www.sciencedirect.com/science/article/pii/S0969996102905164β-AmyloidAlzheimer's diseasemitochondrianeuronastrocyte |
| spellingShingle | C.S. Casley J.M. Land M.A. Sharpe J.B. Clark M.R. Duchen L. Canevari β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical Neurons Neurobiology of Disease β-Amyloid Alzheimer's disease mitochondria neuron astrocyte |
| title | β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical Neurons |
| title_full | β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical Neurons |
| title_fullStr | β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical Neurons |
| title_full_unstemmed | β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical Neurons |
| title_short | β-Amyloid Fragment 25–35 Causes Mitochondrial Dysfunction in Primary Cortical Neurons |
| title_sort | β amyloid fragment 25 35 causes mitochondrial dysfunction in primary cortical neurons |
| topic | β-Amyloid Alzheimer's disease mitochondria neuron astrocyte |
| url | http://www.sciencedirect.com/science/article/pii/S0969996102905164 |
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