Sex differences in motor behavior in the MPTP mouse model of Parkinson's disease.
Sex differences in motor behavior in the MPTP mouse model of Parkinson's disease.
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DOI：
10.1016/j.pbb.2010.03.009
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发表时间：
2010-06
影响因子：
3.6
通讯作者：
Wood, Ruth I.
中科院分区：
文献类型：
--
作者：
Antzoulatos, Eleni;Jakowec, Michael W.;Petzinger, Giselle M.;Wood, Ruth I.
关键词：
在人类和啮齿类动物模型中已报告了帕金森病（PD）的性别差异，男性的发病率较高，雄性啮齿类动物的严重程度增加。目前的研究探讨性别差异和性腺类固醇激素的影响，在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）-损伤的PD小鼠模型。雄性（n=51）和雌性（n=50）小鼠性腺切除，并接受睾酮或雌激素（实验1），或无激素（实验2）的生理替代。两周后，小鼠接受MPTP（每天10 mg/kg，持续5天）或盐水。更高剂量杀死雌性小鼠。在MPTP后一周，使用旋转棒、杆和步态测试来测试小鼠的运动性能。在经雌激素处理的小鼠中，雄性在所有三项测试中均显著优于雌性（p<0.05）。与女性相比，男性具有更高的整体转棒性能（ORP：1317.1±98.3 vs. 988.1±95.6），下降杆更快（7.1±0.6 vs. 9.6±0.7 sec），并且具有更长的步幅（后肢7.3±0.1 vs. 6.8±0.1 cm）。相比之下，接受生理盐水的卵巢切除雌性小鼠在旋转杆上的表现优于去势雄性小鼠（1296.6±83.3对811.2±113.7，p<0.05），并且下降杆更快（9.7±2.0对15.6±1.9秒，p<0.05）。MPTP显著降低了雄性（703.7±65.5）和雌性（432.8±88.6，p<0.05）的ORP（p<0.05）。MPTP后，雄性动物的步长选择性降低（后肢6.6±0.1 cm，p<0.05），两种性别的杆测试表现均未受损。性腺切除后，MPTP没有降低雄性动物的运动能力（p>0.05），但显著降低了雌性动物的ORP（975.9±110.3 vs.生理盐水雌性动物，p<0.05）。我们的研究结果表明，小，慢性剂量的MPTP产生微妙的，性的二态性障碍的运动性能，但没有损失的酪氨酸羟化酶阳性神经元在黑质。在性腺切除的小鼠中，这种性别差异被逆转。
Sex differences in Parkinson's disease (PD) have been reported in humans and rodent models, with a higher incidence in men and increased severity in male rodents. The current study examined sex differences and the effects of gonadal steroid hormones in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of PD. Male (n=51) and female (n=50) mice were gonadectomized and received physiologic replacement with testosterone or estrogen (Experiment 1), or no hormones (Experiment 2). Two weeks later, mice received either MPTP (10mg/kg per day for 5 days) or saline. Higher doses killed female mice. Mice were tested one week after MPTP for motor performance using rotarod, pole and gait tests. In hormone-treated mice, males significantly outperformed females in all three tests (p<0.05). Compared with females, males had a greater overall rotarod performance (ORP: 1317.1±98.3 vs. 988.1±95.6), descended a pole faster (7.1±0.6 vs. 9.6±0.7 sec), and had longer stride lengths (hindlimb 7.3±0.1 vs. 6.8±0.1 cm). By contrast, ovariectomized female mice receiving saline outperformed castrated males on the rotarod (1296.6±83.3 vs. 811.2±113.7, p<0.05) and descended a pole faster (9.7±2.0 vs. 15.6±1.9 sec, p<0.05). MPTP significantly impaired ORP (p<0.05) in hormone-treated males (703.7±65.5) and females (432.8±88.6, p<0.05). After MPTP, stride length was selectively decreased in males (hindlimb 6.6±0.1 cm, p<0.05), and pole test performance was unimpaired in either sex. After gonadectomy, MPTP did not decrease motor performance in males (p>0.05) but significantly reduced ORP in females (975.9±110.3 vs. saline females, p<0.05). Our results show that small, chronic doses of MPTP produce subtle, sexually-dimorphic impairments in motor performance, but without a loss of tyrosine hydroxylase-positive neurons in the substantia nigra. In gonadectomized mice, this sex difference is reversed.
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影响因子：
14.8
作者：
Jackson-Lewis, Vernice;Przedborski, Serge
通讯作者：
Przedborski, Serge
影响因子：
3.2
作者：
Jacob, DA;Temple, JL;Rissman, EF
通讯作者：
Rissman, EF
影响因子：
3.5
作者：
BARKLEY, MS;GOLDMAN, BD
通讯作者：
GOLDMAN, BD
影响因子：
4.8
作者：
Froment, P;Staub, C;Monget, P
通讯作者：
Monget, P
DOI：
10.1006/neur.1995.0016
发表时间：
1995-06-01
期刊：
NEURODEGENERATION
影响因子：
--
作者：
JEON, BS;JACKSONLEWIS, V;BURKE, RE
通讯作者：
BURKE, RE