Degeneration of substantia nigra pars compacta dopamine neurons is a central feature in the pathology of Parkinson's disease, which is characterized by progressive loss of motor and cognitive functions. The largest risk factors for Parkinson's disease are age and sex; most cases occur after age 60 and males have nearly twice the incidence as females. Preclinical work has scarcely considered the influence of these 2 factors to disease risk and presentation. Here, we observed a progressive decline in dopamine neuron firing activity in male C57BL/6 mice by 18 months of age, while dopamine neurons from females remained largely unaffected. This was accompanied by increased mRNA expression of PINK1 in both males and females, and PARK2 primarily in males, both of which have been linked to Parkinson's. Since the declining cell properties were accompanied by only slight decreases in locomotion in both sexes, it is likely that these age-related impairments in males represent a vulnerability to further insults that could predispose the neurons to neurodegenerative processes such as in Parkinson's.

中文翻译：

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雌性小鼠对与年龄相关的黑质多巴胺神经元放电参数下降有弹性

黑质致密部多巴胺神经元的退化是帕金森病病理学的核心特征，其特征在于运动和认知功能的进行性丧失。帕金森病的最大危险因素是年龄和性别；大多数病例发生在 60 岁以后，男性的发病率几乎是女性的两倍。临床前工作几乎没有考虑这两个因素对疾病风险和表现的影响。在这里，我们观察到雄性 C57BL/6 小鼠的多巴胺神经元放电活动在 18 个月大时逐渐下降，而雌性的多巴胺神经元基本上不受影响。这伴随着男性和女性中 PINK1 和 PARK2 主要在男性中的 mRNA 表达增加，这两者都与帕金森氏症有关。