Neuroautoantibody immunoreactivity in relation to aging and stress in apolipoprotein E-deficient mice.
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 approximately 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 approximately 78 kDa and approximately 40 kDa brain abundant polypeptides, approximately 58 kDa non-brain tissue abundant antigen, and others of approximately, 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.
Zhou
Y
Y
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, USA. yzhou2@unl.edu
Cheshire
A
A
Howell
L A
LA
Ryan
D H
DH
Harris
R B
RB
D000375:Aging / Q000276:immunology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009420:Nervous System / Q000276:immunology*; D009490:Neurosecretory Systems / Q000502:physiology; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000276:immunology*
D001057:Apolipoproteins E; D001323:Autoantibodies; D003345:Corticosterone