In a post on 4/6/12, I reviewed a paper by Zhang et al. that provided evidence that anti-streptococcus antibodies can penetrate into the brain and possibly excite neurons in areas relevant for behaviors relevant for PANDAS and OCD. The authors postulated that the antibodies got into the brain because the blood-brain barrier was temporarily opened by the stress evoked in the mice by the injection procedure. Another new paper on this topic by Brimberg and colleagues in Tel Aviv provides more questions and answers for us to discuss. While not entirely novel, this paper is a welcome addition to the controversial field of animal models of PANDAS and Sydenham’s chorea. As in some, but not all, prior work of this type, these authors find that immunizing adult rats with strep causes some modest changes in motor behaviors as well increased self-grooming, which is a proxy for OCD-like behavior. These various behaviors could be reduced by treatment with anti-psychotic (haloperidol) and anti-depression (paroxetine) medications. In addition, the auto-antibodies induced by strep immunization could cross-react against human neuronal antigens. Moreover, these antibodies could be found within the brain itself, as in Zhang paper. However, the authors of the new paper say that antibody penetration of the blood-brain barrier was completely dependent on the injection of an additional bacterial adjuvant into the intraperitoneal cavity, which of course does not happen in PANDAS. So in this rat model, at least, the autoantibodies induced by strep innoculation are not normally found in the brain, in contrast to the Zhang findings. This could be a difference in the species used, mice vs rats, or some other variation in the protocols.
One other finding in this new paper is of particular interest: They provide evidence that sera from Sydenham and PANDAS patients contain antibodies that bind dopamine receptors – proteins important in the behaviors of interest in these disorders. Moreover, they show for 3 patients, at least, the levels of these antibodies go down following “convalescence” (I’m not sure precisely what this term means here). All of this bolsters the case that strep infection can alter behavior by “molecular mimicry” – by inducing auto-antibodies that cross-react with both the pathogen and relevant brain proteins. The question of if and how such antibodies enter the brain remains a critical one.