Brain reactive antibodies and the blood-brain barrier: observations in aging rodents and the effects of peripheral kainic acid.
This study was initiated to confirm the existence of brain-reactive autoantibodies and to determine if such antibodies have higher affinity for brain regions especially affected in Alzheimer's disease. Serum collected from 90, 300, and 600 day old mice was incubated against brain tissues from these same mice, followed by incubation with fluorescently tagged rabbit antimouse IgG. No antibodies were present in the youngest serum, but considerable antibodies were present at 300 and, especially, at 600 days. Such antibodies were present in the blood vessels, but not in the brains of older animals. These antibodies, applied exogenously, labeled cells equally in all three ages of brains including most cortical and many other neurons, indicating that they are not neurotransmitter specific. In a further study, kainic acid or saline was administered peripherally to 15-month old rats. Kainic acid damaged the blood brain barrier and allowed the CNS entry of brain-reactive antibodies, especially into the subregions of hippocampus most damaged in Alzheimer's.
Kulmala
H K
HK
Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272.
Boja
J W
JW
Albrecht
J W
JW
Hutton
J T
JT
D000375:Aging / Q000276:immunology* / Q000502:physiology; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000276:immunology* / Q000502:physiology; D006624:Hippocampus / Q000276:immunology / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011919:Rats, Inbred Strains
D001323:Autoantibodies; D007608:Kainic Acid