Discipline of Physiology, University of Sydney, Australia; Bosch Institute, University of Sydney, Australia.
Brain Res. 2013 Oct 16;1535:61-70. doi: 10.1016/j.brainres.2013.08.047. Epub 2013 Aug 30.
We have examined whether near-infrared light (NIr) treatment mitigates oxidative stress and increased expression of hyperphosphorylated tau in a tau transgenic mouse strain (K3) that has a progressive degeneration of dopaminergic cells in the substantia nigra pars compacta (SNc). The brains of wild-type (WT), untreated K3 and NIr-treated K3 mice, aged five months (thus after the onset of parkinsonian signs and neuropathology), were labelled immunohistochemically for the oxidative stress markers 4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHDG), hyperphosphorylated tau (using the AT8 antibody) and tyrosine hydroxylase (TH). The average intensity and area of 4-HNE, 8-OHDG and AT8 immunoreactivity were measured using the MetaMorph software and TH⁺ cell number was estimated using stereology. Our results showed immunoreactivity for 4-HNE, 8-OHDG and AT8 within the SNc was increased in K3 mice compared to WT, and that this increase was mitigated by NIr. Results further showed that TH⁺ cell number was lower in K3 mice than in WT, and that this loss was mitigated by NIr. In summary, NIr treatment reduced the oxidative stress caused by the tau transgene in the SNc of K3 mice and saved SNc cells from degeneration. Our results, when taken together with those in other models, strengthen the notion that NIr treatment saves dopaminergic cells in the parkinsonian condition.
我们研究了近红外光（NIr）治疗是否可以减轻氧化应激，并减少在一种具有黑质致密部多巴胺能细胞进行性退化的 tau 转基因小鼠品系（K3）中过度磷酸化 tau 的表达。五个月大的野生型（WT）、未治疗的 K3 和 NIr 治疗的 K3 小鼠的大脑通过免疫组织化学方法标记了氧化应激标志物 4-羟壬烯醛（4-HNE）和 8-羟基-2'-脱氧鸟苷（8-OHDG）、过度磷酸化的 tau（使用 AT8 抗体）和酪氨酸羟化酶（TH）。使用 MetaMorph 软件测量 4-HNE、8-OHDG 和 AT8 免疫反应性的平均强度和面积，并使用立体学估计 TH⁺细胞数量。我们的结果表明，与 WT 相比，K3 小鼠的 SNc 中 4-HNE、8-OHDG 和 AT8 的免疫反应性增加，而这种增加被 NIr 减轻。结果还表明，K3 小鼠的 TH⁺细胞数量低于 WT，而这种损失被 NIr 减轻。总之，NIr 治疗减轻了 K3 小鼠 SNc 中 tau 转基因引起的氧化应激，并防止了 SNc 细胞退化。当与其他模型的结果结合起来时，我们的结果增强了 NIr 治疗在帕金森病条件下挽救多巴胺能细胞的观点。
