Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice.
Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice.
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DOI：
10.3389/ftox.2021.722518
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发表时间：
2021
影响因子：
--
通讯作者：
Jones BC
中科院分区：
文献类型：
--
作者：
Torres-Rojas C;Zhao W;Zhuang D;O'Callaghan JP;Lu L;Mulligan MK;Williams RW;Jones BC
百草枯 (PQ) 是引发散发性帕金森病的假定危险因素。为了模拟 PQ 暴露易感性个体差异的可能遗传基础，我们最近研究了百草枯对 BXD 家族小鼠 6 名成员（每品系 2-6 只）黑质致密部 (SNc) 中含有酪氨酸羟化酶 (TH) 的神经元的影响。我们每周给雄性注射 3 次 5 毫克/公斤的百草枯。通过免疫细胞化学在 SNc 的八个或更多切片中以 200 倍计数的 TH+ 神经元密度在六种品系中的五种中相对于对照（N = 4 ± 2 只小鼠/品系）有所降低。 TH+ 损失范围为 0 至 20%，SEM 为 1%。使用标准方差分析和折刀重采样估计遗传力，未治疗动物的遗传力为 0.37 ± 0.05，治疗动物的遗传力为 0.47 ± 0.04。这些结果证明了对 PQ 暴露的易感性的遗传调节和 GxE 变异以及黑质中 TH 染色的丧失。
Paraquat (PQ) is a putative risk factor for the development of sporadic Parkinson’s disease. To model a possible genetic basis for individual differences in susceptibility to exposure to PQ, we recently examined the effects of paraquat on tyrosine hydroxylase (TH)-containing neurons in the substantia nigra pars compacta (SNc) of six members of the BXD family of mice (n = 2–6 per strain). We injected males with 5 mg/kg paraquat weekly three times. The density of TH+ neurons counted by immunocytochemistry at 200x in eight or more sections through the SNc is reduced in five of the six strains relative to control (N = 4 ± 2 mice per strain). TH+ loss ranged from 0 to 20% with an SEM of 1%. The heritability was estimated using standard ANOVA and jackknife resampling and is 0.37 ± 0.05 in untreated animals and 0.47 ± 0.04 in treated animals. These results demonstrate genetic modulation and GxE variation in susceptibility to PQ exposure and the loss of TH staining in the substantia nigra.
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影响因子：
3.6
作者：
Jones BC;Huang X;Mailman RB;Lu L;Williams RW
通讯作者：
Williams RW
影响因子：
3.8
作者：
Torres-Rojas, Carolina;Zhuang, Daming;Jones, Byron C.
通讯作者：
Jones, Byron C.
影响因子：
3.4
作者：
Alam G;Edler M;Burchfield S;Richardson JR
通讯作者：
Richardson JR
影响因子：
3.4
作者：
Alam G;Miller DB;O'Callaghan JP;Lu L;Williams RW;Jones BC
通讯作者：
Jones BC
影响因子：
9.3
作者：
Ashbrook DG;Arends D;Prins P;Mulligan MK;Roy S;Williams EG;Lutz CM;Valenzuela A;Bohl CJ;Ingels JF;McCarty MS;Centeno AG;Hager R;Auwerx J;Lu L;Williams RW
通讯作者：
Williams RW