Population variation in oxidative stress and astrocyte DNA damage in relation to Alzheimer-type pathology in the ageing brain
| Autor: | Paul G. Ince, R. Theaker, Stephen B. Wharton, L. J. Haynes, G Lace, Catherine Gelsthorpe, Lynne Baxter, Julie E. Simpson, Fiona E. Matthews, George M. Savva, G. Forster, Pamela J. Shaw, Carol Brayne |
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| Rok vydání: | 2009 |
| Předmět: |
Senescence
Pathology medicine.medical_specialty Aging Histology DNA repair DNA damage Blotting Western DNA-Activated Protein Kinase Biology medicine.disease_cause Pathology and Forensic Medicine Histones Alzheimer Disease Physiology (medical) medicine Humans Aged Neurons 8-Hydroxy-2'-deoxyguanosine Brain Deoxyguanosine medicine.disease Immunohistochemistry Oxidative Stress medicine.anatomical_structure Neurology Ageing 8-Hydroxy-2'-Deoxyguanosine Astrocytes Neurology (clinical) Alzheimer's disease Oxidative stress Astrocyte DNA Damage |
| Zdroj: | Neuropathology and applied neurobiology. 36(1) |
| ISSN: | 1365-2990 |
| Popis: | Increasing evidence suggests a role for oxidative damage to DNA in brain ageing and in neurodegenerative disorders, including Alzheimer's disease. Most studies have focussed on the reduced capacity for DNA repair by neurones, and have not taken into account the effect of oxidative stress on astrocytes, and their contribution to pathology.We examined levels of oxidative stress, DNA damage and DNA repair mechanisms in astrocytes in a population-based sample derived from the Medical Research Council Cognitive Function and Ageing Neuropathology Study.We demonstrate wide variation in parameters for oxidative stress and DNA damage in astrocytes in the ageing population. We show that there is a significant reduction (P = 0.002) in the lipid peroxidation marker malondialdehyde with increasing Braak stage in Alzheimer's disease. Furthermore, we demonstrate that expression of the DNA damage-associated molecules H2AX and DNA-dependent protein kinase do not increase with increasing Braak stage, rather there is evidence of a nonsignificant reduction in DNA-dependent protein kinase expression by neurones and astrocytes, and in H2AX by neurones with increasing levels of Alzheimer's type pathology.These findings suggest that the changes in oxidative stress and the astrocyte DNA damage response are not accounted for as an accumulating effect due to established Alzheimer-type pathology. We hypothesize that astrocyte damage, leading to impaired function, may contribute to the development of ageing brain pathology in some individuals. |
| Databáze: | OpenAIRE |
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