The Pathophysiologic Mechanism Research Of Dat And Sert And Tcm Syndrom Characteristic Investigation On Tourette Syndrome

Background:Tourette syndrome (TS) is a neurobehavioral and neuropsychiatric disorder and its pathophysiology is not well understood. In addition, obsessive-compulsive behaviour (OCB), Attention Deficit/Hyperactivity Disorder (ADHD), autolesionism and emotional disorder usually associate with TS as common comorbidities, which has affected children's development of cognitive function and perplexed their social adaptation. However, recent studies provide evidence implicating metabolic abnormalities of dopamine (DA) and serotonin (5-HT) of the basal ganglia both in TS patients and TS animal models. It is also well known that dopamine and serotonin transporters (DAT and SERT) are monoamine neurotransmitter transporters, which participate in the metabolism of DA and 5-HT, respectively.Objective:To evaluate whether expression of DAT and SERT in the in the striatum could lead to pathophysiological change in TS rat model.Materials and Methods:Twenty-four Wistar male rats were randomly allocated to:TS model group (n=12) and control group (n=12). The stereotypy counts were recorded during the 2-week period of inducing TS rat models. The levels of DA and 5-HT in striatum homogenate, 5-homovanillic acid (HVIAA) and 5-hydroxyindoleacetic acid (HIAA) were respectively measured by ELISA. The protein and mRNA expression of DAT and SERT in the striatum were tested respectively by Immunofluorescence, Western blot and quantitative real-time PCR.Results:ANOVA analysis indicated that the stereotypy scores were much higher in the TS model group than in the control group at different time points (P<0.01). By ELISA analysis, the DA concentration in striatum homogenate was higher in the TS model group (130.92±25.60ng/ml) than in the control group (101.00±20.14 ng/ml) (P<0.01), but 5-HT concentration in striatum was found to be lower in the TS model group (59.79±14.73ng/ml) compared to the control group (77.01±14.05ng/ml) (P<0.05). Analysis of protein and mRNA levels revealed a lower expression of DAT, concomitant with a higher expression of SERT in striatum of the TS model group than in the control group. Importantly, the correlation between scores of stereotypic behavior and the levels of DAT expression/higher SERT expression in striatums was analysed by Pearson correlation coefficients. Tthe result revealed that higher scores of stereotypic behavior was related to the lower levels of DAT expression/higher SERT expression in striatum (For DAT:r=0.897, n=12, p< 0.001; For SERT:n=12, r=0.913, p<0.001).Conclusions:Lower expression in DAT, concomitant with higher expression in SERT could participate in the pathophysiology of TS. BackgroundTourette syndrome (TS), a chronic neuropsychiatric disorder usually occurs in school-aged children neuropsychiatric disorder, which is characterized by multiple motor and vocal tics, including involuntary or semi-voluntary, sudden, brief, intermittent, repetitive movements or sounds. The prevalence of TS is estimated to be 1-4% in children. It seriously affects the children both in mind and body, and also disturbs their daily life and studies. There are no literature records on TS concept in Traditional Chinese Medicine (TCM), however some similar symptoms were record in TCM including in liver wind, convulsion, hyperspasmia, twitching of eyelids and so on.Typical antipsychotic drugs (e.g. haloperidol, pimozide, and fluphenazine) are widely used in the treatment of TS, but adverse events of toxic and side effects with akathisia, bradykinesia, dystonia, Parkinsonism, and somnolence et al are not tolerant or accepted by TS children and their guardians. Treatment on TS with TCM has shown superior in recent years, however there still are lack of criteria of TCM syndromes, which greatly restrict clinical application of TCM on therapeutic TS.Objective(1) To investigate clinical symptoms and to find the characteristic distribution of TCM symptoms.(2) To provide basic study on syndrome differentiation of TS treated in TCM and to approach the standard research on TCM treatment on TS.Methods Based on our long-term experiment and research, one hundred and twenty-six TS children who was suffered from TS in 4～17 years old, was randomly recruited to take part in the questionnaire survey in the department of integrative medicine on pediatrics, Provincial Hospital Affiliated to Shandong University. The questionary was designed for characteristic syndromes differentiation of TS The questionary was performed from general information, clinical symptoms, urine and feces, syndrome differentiation of TCM, tongue manifestation, and pulse condition.Results(1) Demographic data:ninety-seven male cases accounted for 77% of total 126 TS subjects, thirty-two children had family history of TS and accounted for 25.4%, and the average age was 8.31 years old,64.37 percent in a predominant male in the research.(2) Tic behaviour:tics with facial muscles and tics of limbs are most frequent among all the tics and accounted for 91.6%.(3) Vocal tics:Tics pharyngolaryngeal and parsnasalis vocal are most frequent of vocal tics and accounted for 69.8%.(4) Personality tendency:Impulsiveness accounted for 49.2%, hotheadedness and hyperactivity accounted for 78.6%, and taciturnity accounted for 7.1%.(5) Tongue manifestation:red tongue or deep red tongue accounted for more than 50% among 126 cases.(6) Pulse manifestation:deepwirypulse and slippery pulse almost accounted for 70%.(7) Distribution of characteristic differentiation in TCM:The syndrome types with deficiency of the heart and live, Liver and kidney Yin vacuity type/liver yang overactivity receptively 41.3% and 34.1%.ConclusionDeficiency of the heart and live and Liver and kidney Yin vacuity type/liver yang overactivity type of TCM syndrome are more frequent than the other types, according to which we can formulate the remedial principles for TS including in nourishing Yin and suppressing yang to quench wind or calming liver wind. Furthermore, we can not ignore some other remedial principles for TS including invigoratingthespleen/nourishing heart and reduce phlegm/inseparability of the body and spirit.