title: Multiple mechanisms of age-dependent accumulation of amyloid beta protein in rat brain: Prevention by dietary supplementation with N-acetylcysteine, α-lipoic acid and α-tocopherol.
abstract: The aged brain may be used as a tool to investigate altered metabolism of amyloid beta protein (Aβ42) that may have implications in the pathogenesis of Alzheimer's 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 β 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 Aβ42 in brain cortical tissue of aged rats. Long-term dietary supplementation of rats with a combination of N-acetylcysteine, α-lipoic and α-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, α-lipoic acid and α-tocopherol. The results call for further explorations of this combination in suitable animal models in ameliorating AD related brain deficits.
authors.affiliation: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, 244 A J C Bose Road, Kolkata, India.
authors.forename: Maitrayee
authors.initials: M
authors.lastname: Sinha
authors.affiliation: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, 244 A J C Bose Road, Kolkata, India.
authors.forename: Aritri
authors.initials: A
authors.lastname: Bir
authors.affiliation: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, 244 A J C Bose Road, Kolkata, India.
authors.forename: Anindita
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, 244 A J C Bose Road, Kolkata, India.
authors.forename: Pritha
authors.initials: P
authors.lastname: Bhowmick
authors.affiliation: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, 244 A J C Bose Road, Kolkata, India. Electronic address: profschakrabarti95@gmail.com.
authors.forename: Sasanka
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000008:administration & dosage*; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D008063:Thioctic Acid; D024502:alpha-Tocopherol; D000111:Acetylcysteine
keywords: Alzheimer's disease; Amyloid beta protein; Amyloid precursor protein; Antioxidant; Neprilysin; β Secretase