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) 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 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.