Effects of decreased dopamine transporter levels on nigrostriatal neurons and paraquat/maneb toxicity in mice.
Effects of decreased dopamine transporter levels on nigrostriatal neurons and paraquat/maneb toxicity in mice.
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DOI：
10.1016/j.neurobiolaging.2016.11.015
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发表时间：
2017-03
影响因子：
4.2
通讯作者：
Chesselet MF
中科院分区：
文献类型：
--
作者：
Richter F;Gabby L;McDowell KA;Mulligan CK;De La Rosa K;Sioshansi PC;Mortazavi F;Cely I;Ackerson LC;Tsan L;Murphy NP;Maidment NT;Chesselet MF
How genetic variations in the dopamine transporter (DAT) combined with exposure to environmental toxins modulate the risk of Parkinson’s disease (PD) remains unclear. Using unbiased stereology in DAT knock-down mice (DAT-KD) and wild-type (WT) littermates we found that decreased DAT caused a loss of tyrosine hydroxylase-positive (dopaminergic) neurons in subregions of the substantia nigra pars compacta (SNc) at 3–4 days, 5 weeks, and 18 months of age. Both genotypes lost dopaminergic neurons with age and remaining neurons at 11 months were resilient to paraquat/maneb. In 5 weeks old mice, the toxins decreased SNc dopaminergic neurons in both genotypes but less in DAT-KD. Regional analysis revealed striking differences in the subsets of neurons affected by low DAT, paraquat/maneb, and aging. In particular, we show that a potentially protective effect of low DAT against toxin exposure is not sufficient to reduce death of all nigrostriatal dopaminergic neurons. Thus, different regional vulnerability of nigrostriatal dopaminergic neurons may contribute to an increased risk of developing PD when multiple factors are combined.
