IN VIVO AND IN SILICO STUDIES TO IDENTIFY MECHANISMS ASSOCIATED WITH NURR1 MODULATION FOLLOWING EARLY LIFE EXPOSURE TO PERMETHRIN IN RATS

被引：26
|
作者：
Fedeli, Donatella [1 ]
Montani, Maura [2 ]
Bordoni, Laura [3 ]
Galeazzi, Roberta [4 ]
Nasuti, Cinzia [1 ]
Correia-Sa, Luisa [5 ]
Domingues, Valentina F. [5 ]
Jayant, Maini [6 ]
Brahmachari, Vani [6 ]
Massaccesi, Luca [4 ]
Laudadio, Emiliano [4 ]
Gabbianelli, Rosita [1 ]
机构：
[1] Univ Camerino, Sch Pharm, Via Gentile 3 Varano, I-62032 Camerino, MC, Italy
[2] Univ Camerino, Sch Biosci & Vet Med, Via Gentile 3 Varano, I-62032 Camerino, Italy
[3] Univ Camerino, Sch Adv Studies, Via Gentile 3 Varano, I-62032 Camerino, Italy
[4] Marche Polytech Univ, Dept Life & Environm Sci DISVA, Ancona, Italy
[5] Inst Politecn Porto, REQUIMTE, Inst Super Engn Porto, Rua Dr Antonio Bernardino de Almeida 431, P-4200072 Oporto, Portugal
[6] Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, Epigenet & Dev Biol Grp, Delhi 110007, India
来源：
NEUROSCIENCE | 2017年 / 340卷
关键词：
early life permethrin exposure; Nurr1 promoter methylation; DNMTs; alpha-synuclein; molecular docking; rat; MOLECULAR-DYNAMICS; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; DNA METHYLATION; FORCE-FIELD; CELL-DEATH; DOCKING; NUTRITION; EFFICIENT; QUANTUM;
D O I：
10.1016/j.neuroscience.2016.10.071
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat's life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15 days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated alpha-synuclein protein levels. Adult rats showed enhanced DNMT3b and alpha-synuclein aggregation compared to the control group, while with aging a significant decrease in all biomarkers studied was observed. No changes in Nurr1 promoter methylation in adolescent, adult and old rats were found. In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain. Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：411 / 423
页数：13
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