Animal Models of PANDAS
|Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells
|Behavioral, pharmacological and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disordersFindings: (N=21, C=17) Male rats exposed to GAS antigen exhibited motor issues (impaired food manipulation and beam walking) and compulsive behavior (increase-induced grooming). These symptoms were alleviated with D2 blocker haloperidol and SSRI paroxetine respectively. Antibody deposition appeared in striatum, thalamus, and frontal cortex, with alterations in dopamine and glutamate levels in cortex and basal ganglia. Autoantibodies of GAS rats reacted with tubulin and caused elevated CaM kinase II signaling as found in SC and other neuropsychiatric disorders. The autoantibodies appear to target D1 and D2 receptors in the GAS rats.Critique: While rat response to GAS is distinct from human response, it is interesting that rat auto-antibodies create similar CaM kinase II activation on human cell line.
|Induction of TGF-ß1 and TGF-ß1-dependent predominant Th17 differentiation by group A streptococcal infectionFindings: (match pairs) Female C57BL/6 (B6) and BALB/c mice were inoculated intra nasal with GAS and controls were inoculated in body cavity. T-cell harvesting had elevated Th17 compared with mice inoculated in body cavity (where an expected Th1 response was seen). A particularly unexpected observation was that protective immunity did not prevent invasion of NALT during the first 4 hr after inoculation. This suggests that immune protection is not critical on the nasal epithelium but primarily functions to clear streptococci from NALT.Paper raises question whether only colonization is necessary to affect a Th17 response and that full infection is not needed.
Critique: none noted.
|Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection.Findings: (N=24, C=24). Male and female SJL/J mice immunized with GABHS were found to exhibit substantial behavioral changes. Passive transfer of IgG from immunized mice to naïve mice resulted in similar behavioral abnormalities in the naïve mice.
Critique: It is unclear whether the antibodies are interfering with basal ganglia or only there are increased cytokine responses causing behavioral abnormality. Existence of the antibodies in CSF would need to be found.
|A murine model for neuropsychiatric disorders associated with group A beta-hemolytic streptococcal infectionFindings: (N=20, C=23) Sera from female SJL/J mice immunized with GABHS was found to be immunoreactive to several brain regions. Motoric and behavioral differences noted between immunized and non-immunized mice. Authors provide multiple hypotheses for why there appear differences in the immune response and motoric/behavioral response of the mice. Further research needed.
Critique: None noted.