Multiple mechanisms of age-dependent accumulation of amyloid beta protein in rat brain: Prevention by dietary supplementation with N-acetylcysteine, alpha-lipoic acid and alpha-tocopherol
2016 (English)In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 95, 92-99 p.Article in journal (Refereed) PublishedText
The aged brain may be used as a tool to investigate altered metabolism of amyloid beta protein (A beta 42) that may have implications in the pathogenesis of Alzheimers disease (AD). In the present study, we have observed a striking increase in the amyloid precursor protein (APP) level in the brain cortex of aged rats (22-24 months) along with a mild but statistically significant increase in the level of APP mRNA. Moreover, the activity of beta secretase is elevated (nearly 55%) and that of neprilysin diminished (48%) in brain cortex of aged rats compared to that in young rats (4-6 months). All these changes lead to a markedly increased accumulation of A beta 42 in brain cortical tissue of aged rats. Long-term dietary supplementation of rats with a combination of N-acetylcysteine, alpha-lipoic and alpha-tocopherol from 18 months onwards daily till the sacrifice of the animals by 22-24 months, attenuates the age-related alterations in amyloid beta metabolism. In separate experiments, a significant impairment of spatial learning and memory has been observed in aged rats, and the phenomenon is remarkably prevented by the dietary supplementation of the aged animals by the same combination of N-acetylcysteine, alpha-lipoic acid and alpha-tocopherol. The results call for further explorations of this combination in suitable animal models in ameliorating AD related brain deficits. (C) 2015 Elsevier Ltd. All rights reserved.
Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD , 2016. Vol. 95, 92-99 p.
Amyloid precursor protein; beta Secretase; Neprilysin; Amyloid beta protein; Alzheimers disease; Antioxidant
IdentifiersURN: urn:nbn:se:liu:diva-128956DOI: 10.1016/j.neuint.2015.10.003ISI: 000375515900011PubMedID: 26463138OAI: oai:DiVA.org:liu-128956DiVA: diva2:934892
Funding Agencies|Department of Science and Technology, Govt. of India [SR/SO/HS-78/2008]; BRNS, Dept. of Atomic Energy, Govt. of India2016-06-092016-06-072016-06-27