7,8-DHF Ameliorates L-DOPA-Induced Dyskinesia in a Parkinson’s Disease Rat Model (P5.367)

Objective: To study the effect of activating TrkB receptor in L-DOPA-induced dyskinesia. Background: Parkinson9s disease (PD) is an age-related neurodegenerative movement disorder. L-3,4-dihydroxyphenylalanine (L-DOPA) is still the most effective treatment for PD motor symptoms. Unfortunately, prolonged administration of L-DOPA results in the development of severe motor complications or dyskinesia L-DOPA-induced dyskinesia (LID). Prior research proved that Brain-derived neurotrophic factor (BDNF) plays an important role in the development 7,8-dihydroxyflavone (7,8-DHF) can penetrate the blood brain barrier to activate Tyrosine kinase B (TrkB) receptor, leading to improve content of BDNF in brain. Here we demonstrated role of 7,8-DHF in LID. Methods: We established Parkinson’s disease rat model with destroying the right medial forebrain firstly. Next, 60 successful PD rats were randomly intraperitoneally injected with vehicle, L-DOPA, 7,8-DHF or 7,8-DHF plus L-DOPA for 21 days. Behavioral tests were conducted on day 2, 9, 11, 18 and 21. And then, striatum was separated from rats for western blot, Q-PCR at 21st day. Results: Administration of 7,8-DHF, 30 min before L-DOPA injection, reduced significantly axial, limb, orolingual, and total abnormal index of movement (AIM) scores on day 9, 11,18 and 21 as compared with L-DOPA only. But, 7,8-DHF has no effect on forepaw adjusting steps or rotational response duration which represent curative effect. Western blot showed 7,8-DHF activated TrkB receptor compare with control or L-DOPA group in striatum of lesioned-side. Also, phosphorylation of cAMP-response element binding protein (CREB), a key transcription factor for BNDF, improved. Q-PCR revealed systemic treatment of 7,8-DHF increased the transcriptional level of BDNF in striatum either. Conclusions: We demonstrated that treatment of 7,8-DHF ameliorated LID in PD rats without worsening anti-parkinsonian efficacy of L-DOPA by improving transcription level of BDNF in striatum when 7,8-DHF combined with and activated TrkB receptor. Disclosure: Dr. zhao has nothing to disclose. Dr. Zhen has nothing to disclose. Dr. Shu has nothing to disclose. Dr. Si has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Hu has nothing to disclose. Dr. Huang has nothing to disclose. Dr. Luo has nothing to disclose.