title: Myricitrin Ameliorates 6-Hydroxydopamine-Induced Dopaminergic Neuronal Loss in the Substantia Nigra of Mouse Brain.
abstract: Parkinson's disease (PD) is a chronic and progressive movement disorder, resulting from the degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of DA neuronal loss in PD is still unclear; however, accumulating evidence suggests that treatment with certain flavonoids can induce neuroprotective properties, such as activation of mammalian target of rapamycin complex 1 (mTORC1) and anti-inflammatory activities in animal models of PD. The bioflavonoid myricitrin is well known for its anti-inflammatory and antioxidant properties. However, it is unclear whether systemic treatment with myricitrin can protect neurons against neurotoxin-induced DA degeneration in vivo via the preservation of tyrosine hydroxylase (TH) activity and the induction of mTORC1 activation. Our results found no significant neuroprotective effect of 30 mg/kg myricitrin on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the substantia nigra (SN) of mice. However, myricitrin treatment with 60 mg/kg protected DA neurons against 6-OHDA-induced neurotoxicity. Moreover, myricitrin treatment preserved TH enzyme activity and mTORC1 activation in nigral DA neurons in the SN of 6-OHDA-treated mice, and its treatment suppressed an increase in tumor necrosis factor-α expression in activated microglia. These results suggest that myricitrin may have neuroprotective properties linked to mTORC1 activation, preservation of TH enzyme activity, and anti-neuroinflammation for preventing DA neuronal degeneration in vivo.
authors.affiliation: 1 School of Life Sciences, Kyungpook National University , Daegu, Korea.|2 BK21 plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Korea.
authors.forename: Heung Deok
authors.initials: HD
authors.lastname: Kim
authors.affiliation: 1 School of Life Sciences, Kyungpook National University , Daegu, Korea.
authors.forename: Kyoung Hoon
authors.initials: KH
authors.lastname: Jeong
authors.affiliation: 3 Department of Food Science and Nutrition, Pukyong National University , Busan, Korea.
authors.forename: Un Ju
authors.initials: UJ
authors.lastname: Jung
authors.affiliation: 1 School of Life Sciences, Kyungpook National University , Daegu, Korea.|2 BK21 plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Korea.|4 Brain Science and Engineering Institute, Kyungpook National University , Daegu, Korea.
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Kim
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; C008577:myricitrin; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: 6-hydroxydopamine; dopaminergic neuron; microglia; myricitrin; neuroprotection