The Changes Of Serum Melatonin In Parkinson’s Disease Progression

Objective:1. To investigate the variation of serum melatonin (MLT) levels in different progressof hemiparkinsonium rats, then compared with the levels of MLT in brain microdialyte.2. To investigate the relationship between serum MLT levels and the rotationsinduced by APO and the TH immunoreactive cells in substantia nigra (SN) inhemiparkinsonium rats.3. To investigate the relationship between serum MLT levels and clinical stage of PDpatients, we collected blood sample from PD patients at8:00-10:00, and determine theserum MLT levels.4. To understand the relationship between MLT levels and PD, providing a new ideafor clinical treatment of PD patients.Methods:1. A hemiparkinsonium rat model was established by a unilateral injection of6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc) andthe right medial forebrain bundle (MFB). Blood samples were collected inhemiparkinsonium rats from tail vein at10:00am, at2W,4W,6W and9W, respectively.After centrifugation, the serum MLT levels were determined by enzyme-linkedimmunosorbent assay, and compared the result with the samples from brainmicrodialysis.2. The relationship between serum MLT levels and the changes of DA neurons inSN were assayed by imunohistochemical staining.3. The clinical blood sample was collected from PD patients with Hoehn and Yahr (H&Y) scale I to V and healthy controls at8:00-10:00am. Serum MLT was determinedby ELISA.Results：1. The control and vehicle-treated rats exhibited no marked rotational response toAPO, while the6-OHDA-lesioned rats responded with significantly increased number ofrotations towards the contralateral side (P<0.001). The rotations (in turns/20min, n=5)were191.4±12.98,271.6±26.5,306.4±38.96, and336.6±16.04at2,4,6and9weeks6-OHDA infusion respectively.2. The serum MLT in the control and the vehicle rats at2,4,6and9weeks postlesion showed no significant difference，while there were dramatically increased serumMLT in the PD rats. The serum MLT in the PD rats were significantly increased ascompared to controls and vehicles at2weeks post lesion, and further increased insubsequent weeks (1.97-14.43%per2-3weeks), as compared to controls and vehicles at2week (P<0.05),4(P<0.01),6(P<0.01) and9weeks (P<0.001) post lesion.3. TH immunoreactive positive cells in the lesion side of substantia nigra in PD ratswas significantly lower than that in the contralateral side, and the number of THimmunoreactive positive cells gradually decreased. The TH immunoreactive positivecells in the lesion side of PD rats was decreased75.22%2.12%,81.22%1.32%,87.41%1.04%, and93.1%0.54%compared with the contralateral side respectively at2,4,6and9weeks (2W、4W、6W P<0.001；9W P<0.01，n=5). There were no significantdifference in the lesion side and the contralateral side of the control and the vehiclegroups.4. There was a significant positive correlation between morning serum MLT andAPO-induced turning behavior in PD rats at2,4,6and9weeks, r=0.608，P<0.01(n=20), while there was a significant negative correlation between morning serum MLTand immunoreactive positive cells in the lesion side of PD rats,|r|=0.84，P<0.01(n=20).5. The morning serum MLT levels in PD patients (90.69±5.89pg/ml, n=43) wassignificant higher than that in the control subjects (49.65±1.97pg/ml，n=56), which increased44.85%8.45%compared with the control (P<0.01).The male (87.315.59pg/ml, n=44) and female (103.0718.52pg/ml, n=12) patients with PD was significantlyhigher levels of morning serum MLT compared with the control subjects (52.633.27)pg/ml for males and (46.221.72) pg/ml for females (P<0.05), increased39.25%7.65%and53.35%10.05%respectively.6. There was a significant positive correlation between morning serum MLT and theHoehn and Yahr stage in PD patients (r=0.6, P <0.01).7. The morning serum MLT levels in healthy control group of age≤35,≤55,≤85years old MLT serum levels were (53.800.71pg/ml, n=20),(52.511.02pg/ml, n=16),(49.651.97pg/ml, n=43), and there was no statistically difference in ages, though themorning serum MLT levels were decrease with age increasing.Conclusion:1. Significant increase of serum MLT levels in the model of6-OHDA-inducedhemiparkinsonium rats by weeks may be associated with the progression of PD.2. The serum MLT levels increased in PD patients may be associated with theprogression of PD.3. The serum MLT levels may be an alternative index in severity of PD.