Pienaar I S, Kellaway L A, Russell V A, Smith A D, Stein D J, Zigmond M J, Daniels W M U
Division of Medical Physiology, Department of Biomedical Sciences, University of Stellenbosch, Tygerberg, South Africa.
Stress. 2008 Nov;11(6):448-56. doi: 10.1080/10253890801890721.
Many studies have shown that early life stress may lead to impaired brain development, and may be a risk factor for developing psychiatric pathologies such as depression. However, few studies have investigated the impact that early life stress might have on the onset and development of neurodegenerative disorders, such as Parkinson's disease, which is characterized in part by the degeneration of dopaminergic neurons in the nigrostriatal pathway. The present study subjected rat pups to a maternal separation paradigm that has been shown to model adverse early life events, and investigated the effects that it has on motor deficits induced by a unilateral, intrastriatal injection of 6-hydroxydopamine (12 microg/4 microl). The female rats were assessed for behavioral changes at 28 days post-lesion with a battery of tests that are sensitive to the degree of dopamine loss. The results showed that rats that had been subjected to maternal separation display significantly impaired performance in the vibrissae and single-limb akinesia test when compared to normally reared animals. In addition, there was a significant increase in the loss of tyrosine hydroxylase staining in maternally separated rats. Our results therefore suggest that adverse experiences sustained during early life contribute to making dopamine neurons more susceptible to subsequent insults occurring during more mature stages of life and may therefore play a role in the etiopathogenesis of Parkinson's disease.
许多研究表明，早年生活应激可能导致大脑发育受损，并且可能是罹患诸如抑郁症等精神病理学疾病的一个风险因素。然而，很少有研究调查过早年生活应激可能对神经退行性疾病（如帕金森病）的发病和发展产生的影响，帕金森病的部分特征是黑质纹状体通路中多巴胺能神经元的退化。本研究使幼鼠经历一种已被证明可模拟不良早年生活事件的母性分离范式，并研究其对单侧纹状体内注射6-羟基多巴胺（12微克/4微升）所诱导的运动缺陷的影响。在损伤后28天，使用一系列对多巴胺丧失程度敏感的测试对雌性大鼠的行为变化进行评估。结果显示，与正常饲养的动物相比，经历母性分离的大鼠在触须和单肢运动不能测试中的表现显著受损。此外，经历母性分离的大鼠中酪氨酸羟化酶染色的丧失显著增加。因此，我们的结果表明，早年持续的不良经历会使多巴胺能神经元更容易受到生命更成熟阶段随后发生的损伤影响，因此可能在帕金森病的病因发病机制中起作用。
