Hippocampus of Ames dwarf mice is resistant to β-amyloid-induced tau hyperphosphorylation and changes in apoptosis-regulatory protein levels

Matthew Schrag, Sunita Sharma, Holly Brown-Borg, Othman Ghribi

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The Ames dwarf mouse has a long lifespan and is characterized by a marked resistance to cellular stress, an event that is implicated in the pathogenesis of many neurodegenerative disorders that are associated with aging, including Alzheimer's disease. However, very little is known on the extent to which the Ames dwarf mouse is protected against Alzheimer's disease. We have developed an organotypic slice system cultured from hippocampi of adult dwarf mice and examined deleterious effects of β-amyloid (Aβ) peptide, a key pathogenic event in the course of Alzheimer's disease. We present the first evidence that long living Ames mice resist β-amyloid toxicity. We demonstrate that organotypic slices from adult dwarf mice, but not their normal phenotype counterparts (wild type), are resistant to Aβ25-35-induced hyperphosphorylation of tau protein, reduction in levels of the antiapoptotic protein Bcl-2, increase in levels of the pro-apoptotic protein Bax, and activation of caspase 3. Moreover, incubation of organotypic sections with the GSK-3β inhibitor SB216763 prevented tau phosphorylation but not alterations in levels of Bcl-2, Bax, and caspase-3. Because the hippocampus is a brain area that is severely affected in Alzheimer's disease, our study proposes that organotypic slices from hippocampi of adult Ames dwarf mice may constitute a model system for understanding endogenous factors that may confer protection against Aβ.

Original languageEnglish (US)
Pages (from-to)239-244
Number of pages6
JournalHippocampus
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 25 2008

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Keywords

  • Alzheimer's disease
  • Apoptosis
  • GSK-3β
  • Organotypic slices
  • β-amyloid

ASJC Scopus subject areas

  • Cognitive Neuroscience

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