ENRICHED ENVIRONMENT PROMOTES SIMILAR NEURONAL AND BEHAVIORAL RECOVERY IN A YOUNG AND AGED MOUSE MODEL OF PARKINSON'S DISEASE
ENRICHED ENVIRONMENT PROMOTES SIMILAR NEURONAL AND BEHAVIORAL RECOVERY IN A YOUNG AND AGED MOUSE MODEL OF PARKINSON'S DISEASE
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DOI：
10.1016/j.neuroscience.2010.09.062
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发表时间：
2011-01-13
期刊：
影响因子：
3.3
通讯作者：
Meshul, C. K.
中科院分区：
文献类型：
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作者：
Goldberg, N. R. S.;Haack, A. K.;Meshul, C. K.
环境富集已被证明是1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）帕金森病（PD）小鼠模型的神经保护。由于PD患者通常直到后来的神经病理学阶段才被诊断出来，因此目前的研究调查了丰富环境（EE）刺激黑质神经元（SNpc）恢复的能力和损伤后运动恢复的能力，而不是之前。使用低剂量慢性MPTP方案来实现在急性MPTP模型中未观察到的黑质纹状体通路的部分、不太严重的病变。使用年轻成年（10周）和老年（12个月）C57 BL/6 J雄性小鼠来评估衰老对EE干预的恢复的影响。在MPTP（年轻人7 mg/kg/d;老年人5 mg/kg/d）或盐水注射的第一周后，将来自两组的动物圈养在标准环境（SE）或EE中3周，继续每日施用MPTP。我们是第一个报告，3周后暴露于EE，年轻和老年MPTP损伤的小鼠表现出显着的53%和52%的SNPC中的酪氨酸羟化酶（TH）标记的神经元的恢复，分别。MPTP+EE组TH标记细胞的增加与两个年龄组的独立后部（FSR）行为的恢复相关;然而，仅在老年MPTP+EE组中观察到改善的运动控制（通过每次总活动的足部缺陷（FF）测量）。我们的数据表明，EE促进SNpc神经元中TH蛋白表达的神经恢复，以及在该PD小鼠模型中的年轻和老年动物中的一些运动恢复。由Elsevier Ltd代表IBRO出版。
Environmental enrichment has been shown to be neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Because PD patients are not typically diagnosed until later neuropathological stages, the current study investigated the capacity of an enriched environment (EE) to stimulate restoration of neurons in the substantia nigra pars compacta (SNpc) and locomotor recovery after lesioning, as opposed to before. A low-dose chronic MPTP regimen was used to achieve a partial, less severe lesion of the nigrostriatal pathway not seen in acute MPTP models. Both young adult (10 weeks) and aged (12 months) C57BL/6J male mice were used to assess the effects of aging on recovery with EE intervention. After the first week of either MPTP (7 mg/kg/d in young; 5 mg/kg/d in aged) or saline injection, animals from both groups were housed in a standard environment (SE) or an EE for 3 weeks, with continued daily administration of MPTP. We are the first to report that following 3 weeks exposure to an EE, young and aged MPTP-lesioned mice showed a significant 53% and 52% restoration of tyrosine hydroxylase (TH)-labeled neurons in the SNpc, respectively. This increase in TH-labeled cells in the MPTP+EE group was correlated with recovery of free-standing rear (FSR) behavior in both age groups; however, improved locomotor control as measured by foot faults (FF) per total activity was only seen in the aged MPTP+EE group. Our data demonstrate that an EE promotes neurorestoration in TH protein expression in SNpc neurons as well as some locomotor recovery in both young and aged animals in this mouse model of PD. Published by Elsevier Ltd on behalf of IBRO.