PMID- 32848705
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 12
DP  - 2020
TI  - Lactulose and Melibiose Attenuate MPTP-Induced Parkinson's Disease in Mice by 
      Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation 
      of Autophagy.
PG  - 226
LID - 10.3389/fnagi.2020.00226 [doi]
LID - 226
AB  - 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.
CI  - Copyright (c) 2020 Lin, Wei, Chen, Huang, Lin, Lo, Lin, Lin, Wu, Chang and 
      Lee-Chen.
FAU - Lin, Chih-Hsin
AU  - Lin CH
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Wei, Pei-Cih
AU  - Wei PC
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Chen, Chiung-Mei
AU  - Chen CM
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Huang, Yu-Ting
AU  - Huang YT
AD  - Taipei First Girls High School, Taipei, Taiwan.
FAU - Lin, Jia-Lan
AU  - Lin JL
AD  - Taipei First Girls High School, Taipei, Taiwan.
FAU - Lo, Yen-Shi
AU  - Lo YS
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Lin, Jia-Li
AU  - Lin JL
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Lin, Chung-Yin
AU  - Lin CY
AD  - Medical Imaging Research Center, Institute for Radiological Research, Chang Gung 
      University/Chang Gung Memorial Hospital, Taoyuan, Taiwan.
FAU - Wu, Yih-Ru
AU  - Wu YR
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Chang, Kuo-Hsuan
AU  - Chang KH
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Lee-Chen, Guey-Jen
AU  - Lee-Chen GJ
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20200724
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC7396622
OTO - NOTNLM
OT  - MPTP mice
OT  - Parkinson's disease
OT  - autophagy
OT  - lactulose and melibiose
OT  - neuroinflammation
OT  - oxidative stress
EDAT- 2020/08/28 06:00
MHDA- 2020/08/28 06:01
PMCR- 2020/01/01
CRDT- 2020/08/28 06:00
PHST- 2020/02/17 00:00 [received]
PHST- 2020/06/29 00:00 [accepted]
PHST- 2020/08/28 06:00 [entrez]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2020/08/28 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2020.00226 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2020 Jul 24;12:226. doi: 10.3389/fnagi.2020.00226. 
      eCollection 2020.