title: 7,8-dihydroxyflavone protects 6-OHDA and MPTP induced dopaminergic neurons degeneration through activation of TrkB in rodents.
abstract: Brain-derived neurotrophic factor (BDNF) is a notably important neurotrophin which regulates neuronal survival and differentiation in the nervous system. However, its clinical usage is particularly limited. 7,8-dihydroxyflavone (7,8-DHF), which acts as a selective agonist of BDNF receptor TrkB, is reported to possess neuroprotective effects both in vitro and in vivo. Here we explored the potent neuroprotective effects of 7,8-DHF in 6-OHDA induced rat and MPTP induced mouse model of Parkinsonism. The results demonstrated that treatment with 7,8-DHF in drinking water for four weeks (two weeks before 6-OHDA+two weeks after 6-OHDA lesion) significantly improved dopamine-mediated behaviors in 6-OHDA rat model, and prevented the loss of dopaminergic neurons in the substantia nigra (SN). Phospho-Y816-TrkB immunostaining showed that TrkB phosphorylation was significantly elevated in the SN in 7,8-DHF pretreated group, indicating 7,8-DHF activated TrkB and likely contributed to its neuroprotective effects. 7,8-DHF also protected acute MPTP neurotoxicity in mice but did not affect the climbing behavior in pole test. Thus our study indicates the neuroprotective properties of 7,8-DHF through the activation of TrkB, which provides a novel therapeutic treatment for Parkinson's disease.
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Biology, Sundia MediTech Company Ltd., 388 Jialilve Road, Zhangjiang Hightech Park, Shanghai 201203, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Biology, Sundia MediTech Company Ltd., 388 Jialilve Road, Zhangjiang Hightech Park, Shanghai 201203, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biology, Sundia MediTech Company Ltd., 388 Jialilve Road, Zhangjiang Hightech Park, Shanghai 201203, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Neuropsychiatric Institute, Medical Retardation Research Center, University of California, Los Angeles, CA 90095, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: qyan@yahoo.com.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Biology, Sundia MediTech Company Ltd., 388 Jialilve Road, Zhangjiang Hightech Park, Shanghai 201203, China. Electronic address: zhangsea81@126.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D047309:Flavones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB
chemical_list: C485383:6,7-dihydroxyflavone; D047309:Flavones; D008562:Membrane Glycoproteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C064371:Ntrk2 protein, mouse; C000621230:Ntrk2 protein, rat; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB
keywords: 6-hydroxydopamine; 7,8-dihydroxyflavone; Brain derived neurotrophic factor; MPTP; Neuroprotection; Parkinson’s disease