ABSTRACT
Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on dopaminergic neurons in substantia nigra and nigrostriate fibers in the striatum in cases of Parkinson's disease (PD).Methods Forty male C57BL/6J mice were randomly divided into a control group,a PD model group,a sham-rTMS (srTMS) group and an rTMS group with 10 mice in each group.A PD model was established by subcutaneous injection of a solution of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),and the mice were treated with rTMS or sham rTMS for 14 days.Tyrosine hydroxylase (TH) expression in the substantia and striatum were detected using an immunohistochemical technique,and the corrected optical densities (CODs) of TH in the striatum were analysed using an image analysis system.The Nissl bodies were detected by Nissl staining.The morphological disposition of nerve fibers in the striatum was detected using Warthin-Starry staining.Results The fraction of neurons expressing TH decreased significantly more in the substantia nigras of mice in the rTMS group than in the control group,the PD group and the srTMS group.In the control group the neural plasm of dopaminergic neurons was full of dark blue and granular Nissl bodies.Many Nissl bodies were lost in the PD and srTMS groups,and the remaining Nissl bodies were colored lightly.Few Nissl bodies were lost in the rTMS group.Positive TH reactions in the striatum were significantly decreased in the rTMS group compared to the control group.The average COD was also significantly lower.But positive TH reactions in the striata of the rTMS group mice were significantly greater than in the PD and srTMS groups,and the average COD was significantly higher.In the control group,the disposition of nerve fibers in the striatum was typically fasciculated,concentrated and ordered; in PD and srTMS groups,many fibers were lost,and the remaining nerve fibers were rare,ruptured and scattered ; in the rTMS group fewer nerve fibers were lost and the disposition of the remaining fibers was more fasciculated,concentrated and ordered than in the PD and srTMS groups.Conclusion rTMS may play a role in treating Parkinson's disease by protecting dopaminergic neurons as well as nigrostriate fibers and by improving the synthesis and transport of dopamine.
ABSTRACT
Objective To investigate the effect and its underlying mechanism of repetitive transcranial magnetic stimulation(rTMS)on dopaminergic neurons and glial cell line-derived neurotrophic factor(GDNF)in the substantia nigra(SN)in mice with Parkinson's disease(PD). Methods Thirty-two male C57 BL/6J mice were randomly divided into a normal saline group,a sham-rTMS group,a PD model group and an rTMS group,with 8 mice in each group. All the mice except those in the normal saline group were administered with 4 times of subcutaneous in jection of 1-methyl,4-phenyl-1,2,3,6 tetrahydropyridine(MPTP)15 mg/kg at 2-hour intervals in 1 day to induce neuronal injury in the SN and to establish acute mice PD model.The mice in the rTMS group received 5 trains of 1 Hz rTMS for 25 s,at the intensity of 1 Tesla(T)daily for 2 weeks.After rTMS,the effect of rTMS on PD mice was observed by immunohistoehemieal technique with regard to the expression of tyrosine hydroxylase(TH)and GDNF in the SN,and the quantitative analysis was performed by an advanced image-analysis system. Results Compared with normal saline group,the number of TH and GDNF immunoreaetive(TH-ir and GDNF-ir)cells and the corrected optical density(COD)values of PD model group and sham-rTMS group were significantly lower(P＜0.01);Com pared with PD model and sham-rTMS groups,the numbers of TH and GDNF positive cells and COD values in rTMS group were significantly higher(P＜0.05).There was a significant positive correlation between the count of TH-ir and that of GDNF-ir cells(r=0.836,P＜0.01).The correlation between the COD values of TH-ir and that of GD-NF-ir cells was also significant(r=0.921,P＜0.01).Conclusion rTMS markedly increased the number and the COD values of TH-positive dopaminergic neurons and simultaneously increased the number and the COD value of GD NF-ir cells in the SN of PD mice.These findings suggest that rTMS has neuroprotective effects on dopaminergic neurons in the MPTP-induced PD mice,which might be mediated by up-regulation of the expression of GDNF protein in the SN.