Redox-active Cu(II)-Aβ causes substantial changes in axonal integrity in cultured cortical neurons in an oxidative-stress dependent manner
| Autor: | Claire Howells, William Bennett, Gilles J. Guillemin, Emma D. Eaton, Lana Shabala, Shannon Ray, Adrian K. West, Roger S. Chung, Peep Palumaa, Paul A. Adlard, Katrina Saar |
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| Rok vydání: | 2012 |
| Předmět: |
Dependent manner
Blotting Western Biology medicine.disease_cause Pathogenesis 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Alzheimer Disease medicine Animals Fragmentation (cell biology) Rats Wistar Cells Cultured 030304 developmental biology Cerebral Cortex Neurons 0303 health sciences Amyloid beta-Peptides Neurodegeneration Neurotoxicity Cortical neurons medicine.disease Immunohistochemistry Axons 3. Good health Cell biology Rats Oxidative Stress Neurology Efflux Neuroscience Oxidation-Reduction 030217 neurology & neurosurgery Oxidative stress Copper |
| Zdroj: | Experimental neurology. 237(2) |
| ISSN: | 1090-2430 |
| Popis: | Background: The beta-amyloid (Aβ) peptide comprises the amyloid plaques that characterise Alzheimer's disease (AD), and is thought to significantly contribute towards disease pathogenesis. Oxidative stress is elevated in the AD brain, and there is substantial evidence that the interaction between Aβ and redox-active copper is a major contributing factor towards oxidative stress in AD. Results: The major findings of this study are that redox-active Cu(II)–Aβ causes pronounced axonal pathology in long-term neuronal cultures, including axonal fragmentation and the formation of hyperphosphorylated tau-immunoreactive axonal swellings. Notably, MAP-2 expressing dendritic processes remain largely un-affected by Cu(II)–Aβ treatment. These dystrophic axonal manifestations resemble some of the characteristic neuritic pathology of the AD brain. We show that Cu(II)–Aβ directly causes formation of intra-axonal swellings via the generation of free radicals and subsequent efflux of K + out of neurons. Conclusion: In summary, we report that redox-active Cu(II)–Aβ can induce substantial neurodegenerative changes in mature neurons, and may have an important role to play in the slowly progressing pathogenesis of AD. |
| Databáze: | OpenAIRE |
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