D-serine Ameliorates Motor and Cognitive Impairments in β-amyloid 1-42 Injected Mice by Inhibiting JNK Signaling Pathway.

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 Aβ 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. F-2-Fluro-D-deoxy-glucose positron emission tomography/computed tomography (F-FDG PET/CT) scans were performed to detected glucose metabolism of Aβ 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 Aβ 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.