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Electro-acupuncture (EA), especially high-frequency EA, has been frequently used as an alternative therapy for Parkinsons disease (PD) with reportedly effective for alleviating motor symptoms in patients.However, the physiological and biological mechanism behind its effectiveness is not completely understood.In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), we had discovered that EA stimulation at a high-frequency (100 Hz) significantly reduced apomorphine-induced rotational behavior.And the effects of 100 Hz EA on motor symptoms of Parkinsonian rats involved restoration of the homeostasis of dopaminergic transmission in the basal ganglia circuit.Moreover our previous study has also shown that 100 Hz EA stimulation could up-regulate endogenous neurotrophins and suppress inflammatory responses in the ventral midbrains though the dopamine (DA) content in the striatum did not show any significant change after EA treatment.These results suggest that there are many targets in the PD models for the high frequency EA.So to search for the targets of 100 Hz EA in a full-scale and their functional roles for improving the rotational behavior effect, we selected rat models treated with 6-hydroxydopamine (6-OHDA) into the unilateral MFB, which mimics end-stage PD.Then high throughput microarray analysis was used to uncover the regulated targets by EA in cortex and striatum (STR) after 4 weeks EA treatment.In the differentially regulated transcripts, our results showed that the proportion of recovered expression patterns in the genes were 70.42% in cortex and 78.95% in STR of EA-treated group compared with 6-OHDA-treated group.At the same time, many functional categories regulated by EA and impacted pathways were analyzed.Further, our results suggest that the increased reversion rate of targeted transcripts impacted by 6-OHDA, the recovery of homeostasis in the transcript network, many regulated functional clusters in cortex and STR and much information transfer including immunosuppressive signal transmission from cortex to STR after high-frequency EA treatment may contribute to the behavioral improvement in these rats.