Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Repetitive transcranial magnetic stimulation (rTMS) improves behavioral and biochemical deficits in levodopa-induced dyskinetic rats model

Maowen Ba _, Min Kong, Lina Guan, Maoli Yi and Hongli Zhang

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Oncotarget. 2016; 7:58802-58812. https://doi.org/10.18632/oncotarget.11587

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Abstract

Maowen Ba1,*, Min Kong2,*, Lina Guan1, Maoli Yi3 and Hongli Zhang4

1 Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China

2 Department of Neurology, Yantaishan Hospital, Yantai City, Shandong, PR China

3 Department of Laboratory, Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China

4 Department of Endocrinology, Ruijin Hospital Affiliated To Shanghai Jiaotong University School of Medicine, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Maowen Ba, email:

Keywords: dyskinesia; repetitive transcranial magnetic stimulation (rTMS); dopamine; NR2B; phosphorylation; Gerotarget

Received: July 10, 2016 Accepted: August 21, 2016 Published: August 24, 2016

Abstract

Fluctuations of dopamine levels and upregulations of NR2B tyrosine phosphorylation in the striatum have been connected with levodopa (L-dopa)-induced dyskinesia (LID) in Parkinson’s disease (PD). Repetitive transcranial magnetic stimulation (rTMS) is one of the noninvasive and potential method treating dyskinesia. Yet, the effect of rTMS on the above key pathological events remains unclear. In this study, we gave L-dopa treatment intraperitoneally for 22 days to 6-hydroxydopamine-lesioned PD rats to prepare LID rats model, and subsequently applied rTMS daily for 3 weeks to LID rats model. The effect of rTMS on abnormal involuntary movements (AIMs) was assessed. After ending the experiments, we further determined tyrosine hydroxylase (TH)-positive dopaminergic neurons number by immunohistochemistry, dopamine levels by HPLC, glial cell line-derived neurotrophic factor (GDNF) levels by ELISA, NR2B tyrosine phosphorylation and interactions of NR2B with Fyn by immunoblotting and immunoprecipitation. The results demonstrated that rTMS obviously attenuated AIMs scores, reduced the loss of nigral dopaminergic neurons and the fluctuations of striatal dopamine levels. Meanwhile, rTMS significantly increased the expression of GDNF, which couldrestore the damage of dopaminergic neurons. Additionally, rTMS also reduced the levels of the NR2B tyrosine phosphorylation andits interactions with Fyn in the lesioned striatum of LID rats model. Thus, these data indicate that rTMS can provide benefit for the therapy of LID by improving the key biochemical deficits related to dyskinesia.


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