Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, 4710-057/4805-017 Braga/Guimarães, Portugal.
Int J Mol Sci. 2020 May 14;21(10):3459. doi: 10.3390/ijms21103459.
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.
帕金森病（PD）是第二常见的与年龄相关的神经退行性疾病。导致致残性运动异常的神经退行性变主要发生在黑质纹状体通路，因为黑质致密部（SNpc）中的多巴胺能神经元丧失。已经开发了几种动物模型，不仅可以更好地了解神经退行性变的机制，还可以测试新兴的疾病修饰疗法的潜力。然而，尽管衰老是导致特发性 PD 的主要危险因素，但大多数研究都不使用老年动物。因此，本研究旨在评估衰老对单侧 6-羟多巴胺（6-OHDA）诱导的 PD 动物模型的影响。为此，年轻成年和老年雌性大鼠接受了内侧前脑束的单侧 6-OHDA 注射。随后，评估了衰老对 6-OHDA 诱导的动物福利、运动表现和黑质纹状体完整性的影响。结果表明，衰老对手术后动物福利有负面影响。此外，与年轻大鼠相比，6-OHDA 诱导的熟练运动功能障碍在老年大鼠中更为严重。黑质纹状体组织学分析进一步显示，与年轻动物相比，老年动物的 SNpc 中 6-OHDA 诱导的多巴胺能神经元丧失增加。总的来说，我们的结果表明，老年动物对 6-OHDA 毒性损伤的易感性更高。
