Neuroautoantibody immunoreactivity in relation to aging and stress in apolipoprotein E-deficient mice

You Zhou, Alan Cheshire, Leigh A. Howell, Donna H. Ryan, Ruth B.S. Harris

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Progressive disruption of both the neuroendocrine and immune systems has been correlated with age-associated pathogenesis in patients with Alzheimer's disease and in mice lacking apolipoprotein E (ApoE). In this study, we examined neuroautoimmune and neuroendocrine activities in relation to aging and stress in ApoE-deficient mice. An elevated level of autoantibodies against brain antigens was found in sera from ApoE-deficient mice compared to that of wild-type mice as early as 7-8 weeks of age. However, there was no significant difference between the two genotypes at this age in the effect of stress on serum corticosterone or autoantibody titers. Higher titers of autoantibodies were observed in ~12-week-old ApoE-deficient mice, especially in those exposed to chronic stress. Based on Western analysis, sera from ApoE-deficient mice showed a strong immunoreactivity with ~78 kDa and ~40 kDa brain abundant polypeptides, ~58 kDa non-brain tissue abundant antigen, and others of ~, 80-82 kDa in both the brain and non-brain tissues. Immunofluorescence confocal microscopy showed that the major cellular components recognized by the autoimmune sera from ApoE-deficient mice were associated with neuronal cell nuclei and fiber-like structures in different regions of the brain, including the frontal cortex, lateral cortex and hippocampus. These results suggest that neuroautoimmunity associated with the aging process and exposure to chronic stress may be involved in early development of neurodegeneration in mice with ApoE-deficiency.

Original languageEnglish (US)
Pages (from-to)173-179
Number of pages7
JournalBrain Research Bulletin
Volume49
Issue number3
DOIs
StatePublished - Jun 1 1999
Externally publishedYes

Keywords

  • ApoE-deficient mouse
  • Autoimmune sera
  • Neuroantigens
  • Restraint stress

ASJC Scopus subject areas

  • Neuroscience(all)

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