Abnormal expression of dopamine and serotonin transporters associated with the pathophysiologic mechanism of Tourette syndrome.
BACKGROUND
Tourette syndrome (TS) is a neurobehavioral and neuropsychiatric disorder and its pathophysiology is not well understood. 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 striatum could lead to pathophysiological change in TS rat model.


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 were 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 +/- 25.60 ng/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 +/- 14.73 ng/mL) compared to the control group (77.01 +/- 14.05 ng/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.


CONCLUSIONS
Lower expression in DAT, concomitant with higher expression in SERT could participate in the pathophysiology of TS.
Jijun
Li
L
Department of Integrated Chinese and Western Medicine on Pediatrics, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
Zaiwang
Li
L
Anyuan
Li
L
Shuzhen
Wang
W
Fanghua
Qi
Q
Lin
Zhao
Z
Hong
Lv
L
D000704:Analysis of Variance; D000818:Animals; D002648:Child; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic; D013239:Stereotyped Behavior / Q000502:physiology; D013997:Time Factors; D005879:Tourette Syndrome / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*
D050483:Dopamine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins