MPTP-induced vulnerability of dopamine neurons in A53T α-synuclein overexpressed mice with the potential involvement of DJ-1 downregulation.
10.4196/kjpp.2017.21.6.625
- Author:
Seongmi LEE
1
;
Seung Tack OH
;
Ha Jin JEONG
;
Sok Cheon PAK
;
Hi Joon PARK
;
Jongpil KIM
;
Hyun Seok CHO
;
Songhee JEON
Author Information
1. Department of Biomedical Engineering, Dongguk University, Seoul 04620, Korea.
- Publication Type:Original Article
- Keywords:
Apoptosis;
DJ-1;
MPTP;
Parkinson's disease;
Synuclein
- MeSH:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine;
Adhesives;
Animals;
Apoptosis;
Dopamine*;
Dopaminergic Neurons*;
Down-Regulation*;
Hominidae;
Humans;
Mice*;
Mice, Transgenic;
Neurons;
Parkinson Disease;
Point Mutation;
Synucleins;
Tyrosine 3-Monooxygenase;
Ubiquitin
- From:The Korean Journal of Physiology and Pharmacology
2017;21(6):625-632
- CountryRepublic of Korea
- Language:English
-
Abstract:
Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the α-synuclein (α-syn) gene. Mutant α-syn expression increases the vulnerability of neurons to exogenous insults. In this study, we developed a new PD model in the transgenic mice expressing mutant hemizygous (hemi) or homozygous (homo) A53T α-synuclein (α-syn Tg) and their wildtype (WT) littermates by treatment with sub-toxic (10 mg/kg, i.p., daily for 5 days) or toxic (30 mg/kg, i.p., daily for 5 days) dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Tyrosine hydroxylase and Bcl-2 levels were reduced in the α-syn Tg but not WT mice by sub-toxic MPTP injection. In the adhesive removal test, time to remove paper was significantly increased only in the homo α-syn Tg mice. In the challenging beam test, the hemi and homo α-syn Tg mice spent significantly longer time to traverse as compared to that of WT group. In order to find out responsible proteins related with vulnerability of mutant α-syn expressed neurons, DJ-1 and ubiquitin enzyme expressions were examined. In the SN, DJ-1 and ubiquitin conjugating enzyme, UBE2N, levels were significantly decreased in the α-syn Tg mice. Moreover, A53T α-syn overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest that the vulnerability to oxidative injury such as MPTP of A53T α-syn mice can be explained by downregulation of DJ-1.
