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    題名: Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARr regulation
    作者: Chen, Hwei-Hsien;Chang, Pei-Chi;Wey, Shiaw-Pyng;Chen, Pei-Mei;Chen, Chinpiao;Chan, Ming-Huan
    詹銘煥
    Chan, Ming-Huan
    貢獻者: 神科所
    關鍵詞: 6-Hydroxydopamine;Honokiol;PPARγ;Parkinson’s disease;Positron-emission tomography
    日期: 2018-12
    上傳時間: 2018-12-13 19:56:03 (UTC+8)
    摘要: Parkinson`s disease (PD) is a profound neurodegenerative disorder with gradual loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms. While the current treatment strategies present limitations on halting the progression of PD, this study aimed to investigate the therapeutic potential of honokiol, as a partial peroxisome proliferator-activated receptor-gamma (PPARγ) mimic, on the proceeding behavioral and biochemical alterations in hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral rotation induced by apomorphine at 1-3 weeks post-lesion. Subchronic honokiol administration for 1-2 weeks, beginning 7 days after 6-OHDA-lesion, dose-dependently ameliorated motor dysfunction in hemiparkinsonian mice. Recovery of motor function was correlated with reversal of nigrostriatal dopaminergic neuronal loss, accompanied by higher tyrosine hydroxylase (TH) density, dopamine transporter (DAT) expression and vesicular monoamine transporter-2 (VMAT2) levels. Furthermore, honokiol attenuated oxidative stress and reactive astrocyte induction via decreasing NADPH-oxidase and glial fibrillary acidic protein (GFAP) expressions in 6-OHDA-lesioned striatum. The reversal effects of honokiol on behavioral impairment and striatal PPARγ expression were impeded by PPARγ antagonist GW9662. Notably, subchronic honokiol treatment extended the lifespan of these hemiparkinsonian mice. The present findings demonstrate the therapeutic activities of honokiol in ameliorating motor impairment and progressive dopaminergic damage that could be associated with regulating PPARγ signaling. Therefore, honokiol may potentially exert as a novel therapeutic candidate through PPARγ activation for management of motor symptoms and progressive neurodegeneration in PD.
    關聯: Biomedicine & Pharmacotherapy, Volume 108, Pages 254-262
    資料類型: article
    DOI 連結: http://dx.doi.org/10.1016/j.biopha.2018.07.095
    DOI: 10.1016/j.biopha.2018.07.095
    顯示於類別:[神經科學研究所] 期刊論文

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