Infusion of Sydenham's chorea antibodies in striatum with up-regulated dopaminergic receptors: A pilot study to investigate the potential of SC antibodies to increase dopaminergic activity

Abstract

BackgroundSydenham's chorea (SC) is a neurological manifestation of rheumatic fever. Autoimmune mechanism of SC is supported by clinical improvement with immunomodulatory therapy; presence of circulating serum anti-basal ganglia antibodies; increase in Th2 group of cytokines in serum and CSF of patients. However, a role of the antibodies in the pathogenesis can only be established by their passive transfer. Chorea is a manifestation clearly related to increased dopaminergic (DA) activity. The purpose of this study was to investigate the potential of antibodies from patients with Sydenham's chorea to cause behavior alterations on rats with unilateral post-synaptic dopamine receptor up-regulation. MethodsRats previously submitted to 6-hydroxidopamine (6-OH-DA) unilateral lesion of substantia nigra pars compacta (SNc) and tested with apomorphine to ensure DA receptors up regulation, received intrastriatal infusion of antibodies from SC patients (n=4) or healthy controls (n=3) during 48h. 24h post infusion initiation (24PI) and 48h post infusion initiation (48PI), we registered the occurrence of spontaneous contra lateral rotations (CLR). FindingsSC group exhibited significantly higher number of CLR than control group at 24PI (p=0.049) and 48PI (p=0.048). ConclusionThe limited sample of the present study restricts us to affirm that SC is really an immune-mediated condition. However the significant result of this pilot study points to preliminary evidence that SC antibodies may affect DA activity in rats with up-regulated striatal DA receptors.