Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Department of Environmental Health, University of Fukui School of Medical Sciences, Eiheiji, Fukui, Japan.
Sci Rep. 2024 Mar 28;14(1):7427. doi: 10.1038/s41598-024-57973-4.
Alzheimer's disease (AD), a chronic neurodegenerative disorder, is the leading cause of dementia. Over-activated microglia is related to amyloid-beta (Aβ) and phosphorylated tau (phospho-tau) accumulation in the AD brain. Taurine is an amino acid with multiple physiological functions including anti-inflammatory effects, and has been reported to be neuroprotective in AD. However, the role of taurine in microglia-mediated AD remains unclear. Here, we examined the effects of taurine on the brains of senescence-accelerated mouse prone 8 (SAMP8) mice by comparing those administered 1% taurine water with those administered distilled water (DW). We observed increased levels of taurine and taurine transporter (TAUT) in the brains of the taurine-treated mice compared with those of control mice. Immunohistochemical and Western blot analyses revealed that taurine significantly reduced the number of activated microglia, levels of phospho-tau and Aβ deposit in the hippocampus and cortex. Triggering receptors expressed on myeloid cells-2 (TREM2) are known to protect against AD pathogenesis. Taurine upregulated TREM2 expression in the hippocampus and cortex. In conclusion, the present study suggests that taurine treatment may upregulate TREM2 to protect against microglia over-activation by decreasing the accumulation of phospho-tau and Aβ; providing an insight into a novel preventive strategy in AD.
阿尔茨海默病(AD)是一种慢性神经退行性疾病,是痴呆症的主要病因。过度激活的小胶质细胞与 AD 大脑中的淀粉样蛋白-β(Aβ)和磷酸化 tau(磷酸化 tau)积累有关。牛磺酸是一种具有多种生理功能的氨基酸,具有抗炎作用,据报道在 AD 中具有神经保护作用。然而,牛磺酸在小胶质细胞介导的 AD 中的作用尚不清楚。在这里,我们通过比较给予 1%牛磺酸水的 SAMP8 小鼠和给予蒸馏水(DW)的 SAMP8 小鼠,研究了牛磺酸对 SAMP8 小鼠大脑的影响。与对照组相比,牛磺酸处理组小鼠大脑中的牛磺酸和牛磺酸转运蛋白(TAUT)水平升高。免疫组织化学和 Western blot 分析显示,牛磺酸可显著减少海马体和皮质中活化的小胶质细胞数量、磷酸化 tau 和 Aβ 沉积。髓样细胞表达的触发受体 2(TREM2)已知可保护对抗 AD 发病机制。牛磺酸可上调海马体和皮质中的 TREM2 表达。综上所述,本研究表明,牛磺酸治疗可能通过减少磷酸化 tau 和 Aβ 的积累来上调 TREM2,从而防止小胶质细胞过度激活,为 AD 的预防策略提供了新的思路。