Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy
Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the progressive loss of dopaminergic (DAergic) neurons in the ventral brain. A disaccharide trehalose has demonstrated the potential to mitigate the DAergic loss in disease models for PD. However, trehalose is rapidly hy...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2020.00226/full |
| _version_ | 1819107499506139136 |
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| author | Chih-Hsin Lin Pei-Cih Wei Chiung-Mei Chen Yu-Ting Huang Jia-Lan Lin Yen-Shi Lo Jia-Li Lin Chung-Yin Lin Yih-Ru Wu Kuo-Hsuan Chang Guey-Jen Lee-Chen |
| author_facet | Chih-Hsin Lin Pei-Cih Wei Chiung-Mei Chen Yu-Ting Huang Jia-Lan Lin Yen-Shi Lo Jia-Li Lin Chung-Yin Lin Yih-Ru Wu Kuo-Hsuan Chang Guey-Jen Lee-Chen |
| author_sort | Chih-Hsin Lin |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the progressive loss of dopaminergic (DAergic) neurons in the ventral brain. A disaccharide trehalose has demonstrated the potential to mitigate the DAergic loss in disease models for PD. However, trehalose is rapidly hydrolyzed into glucose by trehalase in the intestine, limiting its potential for clinical practice. Here, we investigated the neuroprotective potential of two trehalase-indigestible analogs, lactulose and melibiose, in sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treatment with MPTP generated significant motor deficits, inhibited dopamine levels, and down-regulated dopamine transporter (DAT) in the striatum. Expression levels of genes involved in anti-oxidative stress pathways, including superoxide dismutase 2 (SOD2), nuclear factor erythroid 2-related factor 2 (NRF2), and NAD(P)H dehydrogenase (NQO1) were also down-regulated. Meanwhile, expression of the oxidative stress marker 4-hydroxynonenal (4-HNE) was up-regulated along with increased microglia and astrocyte reactivity in the ventral midbrain following MPTP treatment. MPTP also reduced the activity of autophagy, evaluated by the autophagosomal marker microtubule-associated protein 1 light chain 3 (LC3)-II. Lactulose and melibiose significantly rescued motor deficits, increased dopamine in the striatum, reduced microglia and astrocyte reactivity as well as decreased levels of 4-HNE. Furthermore, lactulose and melibiose up-regulated SOD2, NRF2, and NQO1 levels, as well as enhanced the LC3-II/LC3-I ratio in the ventral midbrain with MPTP treatment. Our findings indicate the potential of lactulose and melibiose to protect DAergic neurons in PD. |
| first_indexed | 2024-12-22T02:55:01Z |
| format | Article |
| id | doaj.art-1d8786097293497c8f665e0bdeb5344f |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-22T02:55:01Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-1d8786097293497c8f665e0bdeb5344f2022-12-21T18:41:17ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-07-011210.3389/fnagi.2020.00226535670Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of AutophagyChih-Hsin Lin0Pei-Cih Wei1Chiung-Mei Chen2Yu-Ting Huang3Jia-Lan Lin4Yen-Shi Lo5Jia-Li Lin6Chung-Yin Lin7Yih-Ru Wu8Kuo-Hsuan Chang9Guey-Jen Lee-Chen10Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, TaiwanDepartment of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, TaiwanDepartment of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, TaiwanTaipei First Girls High School, Taipei, TaiwanTaipei First Girls High School, Taipei, TaiwanDepartment of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, TaiwanDepartment of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, TaiwanMedical Imaging Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Taoyuan, TaiwanDepartment of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, TaiwanDepartment of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, TaiwanDepartment of Life Science, National Taiwan Normal University, Taipei, TaiwanParkinson’s disease (PD) is a common neurodegenerative disease characterized by the progressive loss of dopaminergic (DAergic) neurons in the ventral brain. A disaccharide trehalose has demonstrated the potential to mitigate the DAergic loss in disease models for PD. However, trehalose is rapidly hydrolyzed into glucose by trehalase in the intestine, limiting its potential for clinical practice. Here, we investigated the neuroprotective potential of two trehalase-indigestible analogs, lactulose and melibiose, in sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treatment with MPTP generated significant motor deficits, inhibited dopamine levels, and down-regulated dopamine transporter (DAT) in the striatum. Expression levels of genes involved in anti-oxidative stress pathways, including superoxide dismutase 2 (SOD2), nuclear factor erythroid 2-related factor 2 (NRF2), and NAD(P)H dehydrogenase (NQO1) were also down-regulated. Meanwhile, expression of the oxidative stress marker 4-hydroxynonenal (4-HNE) was up-regulated along with increased microglia and astrocyte reactivity in the ventral midbrain following MPTP treatment. MPTP also reduced the activity of autophagy, evaluated by the autophagosomal marker microtubule-associated protein 1 light chain 3 (LC3)-II. Lactulose and melibiose significantly rescued motor deficits, increased dopamine in the striatum, reduced microglia and astrocyte reactivity as well as decreased levels of 4-HNE. Furthermore, lactulose and melibiose up-regulated SOD2, NRF2, and NQO1 levels, as well as enhanced the LC3-II/LC3-I ratio in the ventral midbrain with MPTP treatment. Our findings indicate the potential of lactulose and melibiose to protect DAergic neurons in PD.https://www.frontiersin.org/article/10.3389/fnagi.2020.00226/fullParkinson’s diseaselactulose and melibioseMPTP miceoxidative stressneuroinflammationautophagy |
| spellingShingle | Chih-Hsin Lin Pei-Cih Wei Chiung-Mei Chen Yu-Ting Huang Jia-Lan Lin Yen-Shi Lo Jia-Li Lin Chung-Yin Lin Yih-Ru Wu Kuo-Hsuan Chang Guey-Jen Lee-Chen Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy Frontiers in Aging Neuroscience Parkinson’s disease lactulose and melibiose MPTP mice oxidative stress neuroinflammation autophagy |
| title | Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy |
| title_full | Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy |
| title_fullStr | Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy |
| title_full_unstemmed | Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy |
| title_short | Lactulose and Melibiose Attenuate MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy |
| title_sort | lactulose and melibiose attenuate mptp induced parkinson s disease in mice by inhibition of oxidative stress reduction of neuroinflammation and up regulation of autophagy |
| topic | Parkinson’s disease lactulose and melibiose MPTP mice oxidative stress neuroinflammation autophagy |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2020.00226/full |
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