Department of Physiology Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, China.
Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
Neuropharmacology. 2024 Dec 15;261:110159. doi: 10.1016/j.neuropharm.2024.110159. Epub 2024 Sep 18.
Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus, which is an efficient anti-inflammatory agent that functions both in vivo and in vitro. However, it is not clear whether anisomycin can exert neuroprotective effect in AD. In the present study, anisomycin was intragastrically administrated to female triple-transgenic AD (3xTg-AD) model mice, then Morris water maze test was used to observe the long-term spatial memory of mice, the in vivo hippocampal field potential recording was performed to evaluate the synaptic plasticity, the Western blot and immunofluorescence were employed to detect pathological changes, and the bioinformatics analysis was used to predict the potential target of anisomycin exerting effects in AD. The results showed that anisomycin ameliorated the long-term spatial memory deficits, improved LTP depression and increased the expression of PSD-95, reduced the Aβ and tau pathologies, and alleviated the activation of microglia and astrocytes in the brains of 3xTg-AD mice. In addition, the results from bioinformatics analysis showed that the potential target of anisomycin focused on inflammatory pathway. These results indicated that anisomycin exerts neuroprotective effects in 3xTg-AD mice by alleviating neuroinflammation, but the potential mechanism of anisomycin exerting neuroprotective effects needs to be further investigated.
神经炎症在阿尔茨海默病（AD）的发病机制中起着关键作用。放线菌酮是一种从灰色链霉菌中分离出来的吡咯烷抗生素，是一种有效的抗炎剂，在体内和体外都具有抗炎作用。然而，目前尚不清楚放线菌酮是否能在 AD 中发挥神经保护作用。在本研究中，将放线菌酮灌胃给予雌性三转基因 AD（3xTg-AD）模型小鼠，然后通过 Morris 水迷宫测试观察小鼠的长期空间记忆，通过体内海马场电位记录评估突触可塑性，通过 Western blot 和免疫荧光检测病理变化，并进行生物信息学分析以预测放线菌酮在 AD 中发挥作用的潜在靶标。结果表明，放线菌酮改善了 3xTg-AD 小鼠的长期空间记忆缺陷，改善了 LTP 抑制，增加了 PSD-95 的表达，减少了 Aβ和 tau 病理学，并减轻了 3xTg-AD 小鼠大脑中小胶质细胞和星形胶质细胞的激活。此外，生物信息学分析的结果表明，放线菌酮的潜在靶标集中在炎症途径上。这些结果表明，放线菌酮通过减轻神经炎症在 3xTg-AD 小鼠中发挥神经保护作用，但放线菌酮发挥神经保护作用的潜在机制仍需进一步研究。
