Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, #74, Zhongshan 2nd Road, Guangzhou 510080, China.
Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Neuroscience. 2018 Mar 1;373:52-59. doi: 10.1016/j.neuroscience.2018.01.002. Epub 2018 Jan 11.
Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau, tau, tau mice. We found tau deficiency could not induce significant motor disorders. However, we discovered lower expression levels of transcription factors Orthodenticle homeobox 2 (OTX2) of mDANs in older aged mice. Compared with age-matched tau mice, there were 54.1% lower (p = 0.0192) OTX2 protein (OTX2-fluorescence intensity) in VTA DA neurons of tau mice and 43.6% lower (p = 0.0249) OTX2 protein in VTA DA neurons of tau mice at 18 months old. Combined with the relevant reports, our results suggested that tau deficiency alone might not be enough to mimic the pathology of Parkinson's disease. However, OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more sensitive to toxic damage from MPTP.
tau 蛋白参与微管稳定、轴突运输和蛋白运输。tau 蛋白正常功能的丧失将产生负面影响。然而，目前关于 tau 缺乏对运动行为和相关神经生物学变化影响的知识存在争议。在这项研究中，我们检查了运动功能，并分析了几种与维持中脑多巴胺能 (mDAN) 神经元功能相关的蛋白质，这些蛋白质在成年和老年 tau、tau、tau 小鼠中都有表达。我们发现 tau 缺乏不能诱导明显的运动障碍。然而，我们发现老年 tau 小鼠的 mDANs 中转录因子 Orthodenticle homeobox 2 (OTX2) 的表达水平较低。与年龄匹配的 tau 小鼠相比，tau 小鼠 VTA DA 神经元中的 OTX2 蛋白（OTX2-荧光强度）降低了 54.1%（p=0.0192），18 个月大的 tau 小鼠 VTA DA 神经元中的 OTX2 蛋白降低了 43.6%（p=0.0249）。结合相关报道，我们的结果表明，tau 缺乏本身可能不足以模拟帕金森病的病理学。然而，OTX2 的下调表明，tau 缺乏小鼠的 mDANs 对 MPTP 的毒性损伤将更加敏感。
