Parkinson’s disease (PD) is caused by neurodegeneration of nigrostriatal neurons, resulting in dopamine (DA) stimulated motor deficits. Like brain derived neurotrophic factor (BDNF), 7,8-dihydroxyflavone (DHF) is an agonist of the tropomyosin receptor kinase-B (TrkB) receptor and stimulates the same secondary cascades that promote neuronal growth, survival and differentiation. We used our progressive mouse model of PD by administering increasing doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over 4 weeks (5 days/week), and then treated mice with DHF for 4 weeks after the cessation of the toxin injections (i.e., restoration). Mice treated with DHF recovered motorically, even after MPTP administration. Despite a 75% loss of tyrosine hydroxylase (TH) expression in the dorsolateral (DL) striatum in the MPTP group, mice treated with DHF had a full recovery comparable to that found in the respective control. There was no recovery of DA tissue levels within the DL striatum. In both the DL striatum and substantia nigra (SN)/midbrain, phosphorylated TrkB and secondary messengers were significantly increased following DHF compared to the MPTP only group. Expression of the sprouting biomarker, superior cervical ganglion 10 (SCG10), was increased ∼20% in the DL striatum and 66% in the SN/midbrain in mice treated with DHF compared to the MPTP only group. We report that after 4 weeks of progressive MPTP administration, DHF can restore motor deficits and TH within the DL striatum in a TrkB-dependent manner. Our data suggests that DHF may help alleviate motor symptoms of PD and restore the loss of DA terminals within the striatum.

帕金森氏病（PD）是由黑纹状体神经元的神经变性引起的，导致多巴胺（DA）刺激的运动功能障碍。像脑源性神经营养因子（BDNF）一样，7,8-二羟基黄酮（DHF）是原肌球蛋白受体激酶B（TrkB）受体的激动剂，并刺激促进神经元生长，存活和分化的相同次级级联反应。我们通过在4周内（5天/周）给予递增剂量的1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）来使用PD的渐进性小鼠模型，然后用DHF处理小鼠停止注射毒素后4周（即恢复）。即使使用MPTP，用DHF处理的小鼠也能运动恢复。尽管MPTP组的背外侧（DL）纹状体中酪氨酸羟化酶（TH）表达减少了75％，用DHF处理的小鼠的完全恢复与相应对照组中的恢复相当。DL纹状体内DA组织水平没有恢复。在DL纹状体和黑质（SN）/中脑中，与仅使用MPTP组相比，DHF后磷酸化的TrkB和次级信使均显着增加。与仅使用MPTP组相比，用DHF处理的小鼠的DL纹状体中发芽的生物标志物上颈神经节10（SCG10）的表达增加了约20％，而SN /中脑的表达则增加了约66％。我们报告说，在进行MPTP渐进管理4周后，DHF可以以TrkB依赖的方式恢复DL纹状体内的运动功能障碍和TH。我们的数据表明DHF可能有助于减轻PD的运动症状并恢复纹状体内DA末端的丢失。