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Mechanism of Tourette Syndrome Induced by ABGA-Mediated CaMKII-TH Pathway
Xinnan Wu1, Juanjuan Hao2, Keyu Jiang1
1Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
In this study, we intend to investigate the mechanism by which anti-basal ganglia antibodies (ABGA) modulate dopamine release through the CaMKII-TH pathway, which leads to the onset of Tourette syndrome (TS).
Methods:
In the clinical experiment, serum samples were collected from 40 TS children and 40 healthy children. ELISA was performed to detect ABGA, anti-streptolysin O (ASO), and anti-deoxyribonuclease B (ADNB) levels in each group. In the animal experiment, the TS group was microinfused with ABGA-positive serum from TS children. The expression levels of striatal pCaMKIIα/CaMKIIα, pTH/TH, Drd1, Drd2, and dopamine (DA) were detected.
Results:
Clinical experiments showed positive correlation between serum ABGA, ASO, ADNB levels, and YGTSS scores. Animal experiments showed that the stereotype score and the expression levels of striatal pCaMKIIα/CaMKIIα, pTH/TH, Drd1, and DA were increased in the TS group. The expression levels of striatal Drd2 were reduced, accompanied by neuronal loss within the striatum in the TS group.
Conclusion:
ABGA may contribute to the development of TS by increasing striatal dopamine levels through the activation of calcium-calmodulin dependent protein kinase II (CaMKIIα) phosphorylation and tyrosine hydroxylase (TH) phosphorylation.
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