Sunday, January 21, 2007

Autoantibodies may influence memory

Most lupus patients have serum autoantibodies against double-stranded DNA (dsDNA) and some suffer from cognitive impairment and mood disturbance, symptoms of neuropsychiatric lupus (NPSLE). These researchers previously used phage display to find a pentapeptide that crossreacts with a pathogenic, monoclonal, dsDNA-specific autoantibody. They further found that the mouse and human receptors for the neurotransmitters NMDA (N-methyl-D-aspartate) and glutamate, NR2a and NR2b, contain this pentapeptide. They also showed that mice immunized with the pentapeptide developed antibodies that bound NR2 but did not cause neural injury unless the blood-brain-barrier (BBB) was disturbed. Similar antibodies can be detected in the cerebrospinal fluid of SLE patients but not healthy control subjects. Administering LPS to these immunized mice opened the BBB in the hippocampus, leading to antibody binding and cell loss in this area of the brain. The treated mice performed poorly in maze tests, suggesting memory impairment. Now, they show that administering epinephrine opened the BBB in the amygdala, exposing cells there to the toxic autoantibodies. The treated mice were less fearful. These may be seminal papers in understanding cognitive defects."
Huerta PT, Kowal C, Degiorgio LA, Volpe BT, Diamond B. "Immunity and behavior: Antibodies alter emotion." Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):678-83.

No comments: