The senile plaque formed by β-amyloid (Aβ) deposition in the brain is one of the main pathological features of Alzheimer's disease (AD), and the c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in the pathogenesis of AD. This study aimed to investigate that D-serine may ameliorate motor and cognitive impairment in Aβ injected mice by inhibiting JNK signaling pathway. Firstly, Kunming mice were injected intrahippocampally with Aβ1-42 to build AD model. The mice were injected intraperitoneally with saline, D-serine, D-amino acid oxidase (DAAO), and Sodium benzoate (BE) for 10 consecutive days, respectively. Subsequently, the motor and cognitive functions of mice were detected by behavioral tests. The silver staining and immunohistochemical methods were used to detect the distributions of Aβ in the hippocampus of mice. 18F-2-Fluro-D-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans were performed to detected glucose metabolism of Aβ1-42 induced lesions. The expressions of relative JNK factors were detected by immunohistochemistry and Western blot methods. These results showed that Aβ severely impaired the motor and memory abilities of mice. The expressions of glial fibrillary acidic protein (GFAP), tumor necrosis factor (TNF-α), N-methyl-D-aspartate receptor 1 (NMDAR1), phospho-JNK (p-JNK), p-c-Jun and activating transcription factor 2 (ATF2) increased significantly. After D-serine treatment, the abilities of movement and memory of mice were improved, and the clearance rate of Aβ was accelerated. The expressions of GFAP, TNF-α, NMDAR1, p-JNK, p-c-Jun and ATF2 decreased significantly. DAAO and BE were administered to further validate these results. Therefore, this study showed that D-serine could alleviate the cognitive impairment of Aβ1-42 injected mice by inhibiting JNK signaling pathway. These results provide more evidences for the effect of D-serine on AD and relevant mechanism to treat AD.

中文翻译：

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D-丝氨酸通过抑制 JNK 信号通路改善注射 β-淀粉样蛋白 1-42 的小鼠的运动和认知障碍

脑内β-淀粉样蛋白（Aβ）沉积形成的老年斑是阿尔茨海默病（AD）的主要病理特征之一，c-Jun N-末端激酶（JNK）信号通路在发病机制中起重要作用的广告。本研究旨在探讨 D-丝氨酸可能通过抑制 JNK 信号通路改善注射 Aβ 小鼠的运动和认知障碍。首先，昆明小鼠海马内注射Aβ1-42建立AD模型。小鼠分别连续 10 天腹腔注射生理盐水、D-丝氨酸、D-氨基酸氧化酶 (DAAO) 和苯甲酸钠 (BE)。随后，通过行为测试检测小鼠的运动和认知功能。采用银染和免疫组化方法检测小鼠海马区Aβ的分布。进行 18F-2-氟-D-脱氧-葡萄糖正电子发射断层扫描/计算机断层扫描 (18F-FDG PET/CT) 扫描以检测 Aβ1-42 诱导病变的葡萄糖代谢。采用免疫组织化学和Western blot方法检测相关JNK因子的表达。这些结果表明 Aβ 严重损害了小鼠的运动和记忆能力。胶质纤维酸性蛋白（GFAP）、肿瘤坏死因子（TNF-α）、N-甲基-D-天冬氨酸受体1（NMDAR1）、磷酸化-JNK（p-JNK）、pc-Jun和激活转录因子2的表达(ATF2) 显着增加。D-丝氨酸治疗后小鼠运动记忆能力提高，Aβ清除率加快。GFAP、TNF-α、NMDAR1、p-JNK、pc-Jun和ATF2的表达显着降低。管理 DAAO 和 BE 以进一步验证这些结果。因此，本研究表明D-丝氨酸可以通过抑制JNK信号通路减轻Aβ1-42注射小鼠的认知障碍。这些结果为D-丝氨酸对AD的作用及治疗AD的相关机制提供了更多的证据。