Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: Implications for aging and age-related neurodegenerative disorders

H. Fai Poon, Susan A. Farr, Visith Thongboonkerd, Bert C. Lynn, William A. Banks, John E. Morley, Jon B. Klein, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

Free radical-mediated damage to neuronal membrane components has been implicated in the etiology of Alzheimer's disease (AD) and aging. The senescence accelerated prone mouse strain 8 (SAMP8) exhibits age-related deterioration in memory and learning along with increased oxidative markers. Therefore, SAMP8 is a suitable model to study brain aging and, since aging is the major risk factor for AD and SAMP8 exhibits many of the biochemical findings of AD, perhaps as a model for and the early phase of AD. Our previous studies reported higher oxidative stress markers in brains of 12-month-old SAMP8 mice when compared to that of 4-month-old SAMP8 mice. Further, we have previously shown that injecting the mice with α-lipoic acid (LA) reversed brain lipid peroxidation, protein oxidation, as well as the learning and memory impairments in SAMP8 mice. Recently, we reported the use of proteomics to identify proteins that are expressed differently and/ or modified oxidatively in aged SAMP8 brains. In order to understand how LA reverses the learning and memory deficits of aged SAMP8 mice, in the current study, we used proteomics to compare the expression levels and specific carbonyl levels of proteins in brains from 12-month-old SAMP8 mice treated or not treated with LA. We found that the expressions of the three brain proteins (neurofilament triplet L protein, α-enolase, and ubiquitous mitochondrial creatine kinase) were increased significantly and that the specific carbonyl levels of the three brain proteins (lactate dehydrogenase B, dihydropyrimidinase-like protein 2, and α-enolase) were significantly decreased in the aged SAMP8 mice treated with LA. These findings suggest that the improved learning and memory observed in LA-injected SAMP8 mice may be related to the restoration of the normal condition of specific proteins in aged SAMP8 mouse brain. Moreover, our current study implicates neurofilament triplet L protein, α-enolase, ubiquitous mitochondrial creatine kinase, lactate dehydrogenase B, and dihydropyrimidinase-like protein 2 in process associated with learning and memory of SAMP8 mice.

Original languageEnglish
Pages (from-to)159-168
Number of pages10
JournalNeurochemistry International
Volume46
Issue number2
DOIs
StatePublished - Jan 2005

Bibliographical note

Funding Information:
This work was supported in part by grants from NIH to D.A.B. [AG-05119; AG-10836] and by VA Merit Review (W.A.B.).

Keywords

  • Aging
  • Alzheimer's disease
  • Brain protein
  • Oxidative modification effects on learning and memory
  • Proteomics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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