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Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death.
Sci Rep. 2017 04 12; 7:45741.SR

Abstract

Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content. At the same time, apomorphine-induced turning behavior was evident in rats subjected to a unilateral infusion of acrolein in SN. Acrolein was pro-oxidative by increasing 4-hydroxy-2-nonenal and heme oxygenase-1 levels. Furthermore, acrolein conjugated with proteins at lysine residue and induced α-synuclein aggregation in the infused SN. Acrolein was pro-inflammatory by activating astrocytes and microglia. In addition, acrolein activated caspase 1 in the infused SN, suggesting acrolein-induced inflammasome formation. The neurotoxic mechanisms underlying acrolein-induced neurotoxicity involved programmed cell death, including apoptosis and necroptosis. Compared with well-known Parkinsonian neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone which do not exist in the SN of PD patients, our in vivo study shows that acrolein acts as a Parkinsonian neurotoxin in the nigrostriatal dopaminergic system of rat brain.

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Authors+Show Affiliations

Wang YT
Institute of Physiology, National Yang Ming University, Taipei, Taiwan.
Lin HC
Institute of Physiology, National Yang Ming University, Taipei, Taiwan.
Zhao WZ
Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan.
Huang HJ
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
Lo YL
Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan.
Wang HT
Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan.
Lin AM
Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan.

MeSH

AcroleinAnimalsCell DeathDisease Models, AnimalDopaminergic NeuronsEncephalitisMaleOxidative StressParkinsonian DisordersProtein Aggregation, PathologicalRats, Sprague-DawleySubstantia Nigraalpha-Synuclein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28401906

Citation

Wang, Yi-Ting, et al. "Acrolein Acts as a Neurotoxin in the Nigrostriatal Dopaminergic System of Rat: Involvement of Α-synuclein Aggregation and Programmed Cell Death." Scientific Reports, vol. 7, 2017, p. 45741.
Wang YT, Lin HC, Zhao WZ, et al. Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death. Sci Rep. 2017;7:45741.
Wang, Y. T., Lin, H. C., Zhao, W. Z., Huang, H. J., Lo, Y. L., Wang, H. T., & Lin, A. M. (2017). Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death. Scientific Reports, 7, 45741. https://doi.org/10.1038/srep45741
Wang YT, et al. Acrolein Acts as a Neurotoxin in the Nigrostriatal Dopaminergic System of Rat: Involvement of Α-synuclein Aggregation and Programmed Cell Death. Sci Rep. 2017 04 12;7:45741. PubMed PMID: 28401906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death. AU - Wang,Yi-Ting, AU - Lin,Hui-Ching, AU - Zhao,Wei-Zhong, AU - Huang,Hui-Ju, AU - Lo,Yu-Li, AU - Wang,Hsiang-Tsui, AU - Lin,Anya Maan-Yuh, Y1 - 2017/04/12/ PY - 2016/10/03/received PY - 2017/03/06/accepted PY - 2017/4/13/entrez PY - 2017/4/13/pubmed PY - 2018/11/18/medline SP - 45741 EP - 45741 JF - Scientific reports JO - Sci Rep VL - 7 N2 - Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content. At the same time, apomorphine-induced turning behavior was evident in rats subjected to a unilateral infusion of acrolein in SN. Acrolein was pro-oxidative by increasing 4-hydroxy-2-nonenal and heme oxygenase-1 levels. Furthermore, acrolein conjugated with proteins at lysine residue and induced α-synuclein aggregation in the infused SN. Acrolein was pro-inflammatory by activating astrocytes and microglia. In addition, acrolein activated caspase 1 in the infused SN, suggesting acrolein-induced inflammasome formation. The neurotoxic mechanisms underlying acrolein-induced neurotoxicity involved programmed cell death, including apoptosis and necroptosis. Compared with well-known Parkinsonian neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone which do not exist in the SN of PD patients, our in vivo study shows that acrolein acts as a Parkinsonian neurotoxin in the nigrostriatal dopaminergic system of rat brain. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28401906/Acrolein_acts_as_a_neurotoxin_in_the_nigrostriatal_dopaminergic_system_of_rat:_involvement_of_α_synuclein_aggregation_and_programmed_cell_death_ DB - PRIME DP - Unbound Medicine ER -
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