Repetitive transcranial magnetic stimulation (rTMS) improves behavioral and biochemical deficits in levodopa-induced dyskinetic rats model.
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.
Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China.
Maowen
M
Ba
Department of Neurology, Yantaishan Hospital, Yantai City, Shandong, PR China.
Min
M
Kong
Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China.
Lina
L
Guan
Department of Laboratory, Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China.
Maoli
M
Yi
Department of Endocrinology, Ruijin Hospital Affiliated To Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
Hongli
H
Zhang
D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000502:physiology*; D004409:Dyskinesia, Drug-Induced / Q000628:therapy*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D007980:Levodopa; D010300:Parkinson Disease / Q000628:therapy*; D000066553:Problem Behavior; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D050781:Transcranial Magnetic Stimulation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D004298:Dopamine
Gerotarget; NR2B; dopamine; dyskinesia; phosphorylation; repetitive transcranial magnetic stimulation (rTMS)