Oxidative stress in a rat model of chronic gliosis.
Alzheimer's disease is a progressive neurodegenerative disorder characterised by abnormal extracellular deposition of a 4 kDa peptide termed beta-amyloid, neuronal loss, oxidative stress and chronic astrocytosis and microgliosis, but how the latter two features contribute to the progression of the disease is poorly understood. We have previously demonstrated in a novel in vivo transplantation model that chronic astro- and microgliosis resulted in molecular pathology similar to that observed in the Alzheimer's disease brain. We now report that these heterotopic, gliotic transplants exhibit prolonged oxidative stress, characterised by lipid peroxidation and protein carbonyl formation. Furthermore, we demonstrate that dietary additives can elevate endogenous anti-oxidant defences and reduce oxidative stress without attenuating astro- and microgliosis. We also show that administration of ibuprofen through the drinking water results in a similar reduction in oxidative stress but with no observable effect on glial reactivity. The present study lends support to the notion that dietary anti-oxidants and non-steroidal anti-inflammatory drugs may be potential preventative agents against some of the pathological processes associated with neurodegenerative disease.
Bates
Kristyn A
KA
School of Anatomy and Human Biology, University of Western Australia, Nedlands, WA, Australia. k.bates@ecu.edu.au <k.bates@ecu.edu.au>
Martins
Ralph N
RN
Harvey
Alan R
AR
D000111:Acetylcysteine / Q000627:therapeutic use; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001253:Astrocytes / Q000637:transplantation; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D016332:Fetal Tissue Transplantation / Q000379:methods; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000503:physiopathology* / Q000628:therapy; D007052:Ibuprofen / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D000447:Aldehydes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D005904:Glial Fibrillary Acidic Protein; C027576:4-hydroxy-2-nonenal; D007052:Ibuprofen; D000111:Acetylcysteine