Third, regulation by miRNAs occurs at the network level. In this study, we selectively investigated the function of let-7b, but other miRNAs that contributed to the disease and their communication with let-7b, especially for the up-stream signal of let-7b and its role in CTEPH, still needed further study and evaluation. Fourth, our previous study of miRNA profile of PASMCs culture from pulmonary endarterectomy tissue also found let-7d, another member of let-7 family, was decreased and involved in the cell proliferation, which indicated the importance of let-7 family in pathogenesis of CTEPH. A hypothesis about the mechanism leading to the decrease of let-7 family is still needed to be set in our further study.The present study replicated and extended our previous findings regarding the effects of exposure of rats to GAS extract. Immunologically, exposure to GAS led to an increase in sera antiGAS antibodies as well as to the presence of antibodies in the striatum, PFC and thalamus, as we have previously found. Behaviorally, GAS exposure led to impaired food manipulation and increased marble-burying without a concomitant increase in activity level. These behavioral alterations may be relevant to symptoms commonly observed in GAS-related neuropsychiatric disorders, including impaired fine motor control, anxiety and compulsions. A novel finding of the present study is that GAS-exposure led to an increase in the level of TH and of D1 and D2 dopamine receptors in the striatum and PFC. These results add to our previous findings of altered dopamine function following GAS exposure. Specifically, the D2 antagonist, haloperidol, ameliorated motor impairment in GAS-exposed rats ; anti-D1 and anti-D2 IgG were detected in the sera of these rats ; and their dopamine level in the frontal cortex and basal ganglia was increased. Involvement of the dopaminergic system has been repeatedly implicated in the pathogenesis of GAS-related neuropsychiatric disorders: Anti-dopaminergic drugs such as haloperidol are used to treat motor symptoms in GAS-related disorders ; anti-D1 and anti-D2 antibodies were detected in the sera of SC and PANDAS patients ; and increased levels of TH were found in brains of rats injected with antibodies purified from SC patients. Interestingly, sera and IgG from SC and PANDAS patients and from GAS-exposed rats led to increased CAM-KII activity in vitro, and CAM-KII activity has been shown to up-regulate the D2 dopamine receptor promoter in vitro. There are previous reports that antibodies to neuronal cell surface can lead to changes in the function and level of their targeted protein, thus leading to neuronal and behavioral alterations. For instance, anti-AMPA receptor antibodies in AMPA receptor encephalitis as well as WY 14643 anti-NMDA receptor antibodies in anti-NMDA receptor encephalitis and in paraneoplastic syndrome were reported to decrease synaptic density of the receptor.