The protective effect and its underlying mechanism of repetitive transcraniai magnetic stimulation on dopaminergic neurons in the substantia nigra of mice with Parkinson's disease / 中华物理医学与康复杂志

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.