Zhao Ting Ting, Kim Kyung Sook, Shin Keon Sung, Park Hyun Jin, Kim Hyun Jeong, Lee Kyung Eun, Lee Myung Koo
Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju, 28644, Republic of Korea.
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, Cheongju, 28644, Republic of Korea.
BMC Complement Altern Med. 2017 Sep 6;17(1):449. doi: 10.1186/s12906-017-1959-x.
Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA).
MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation.
MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg).
GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant therapeutic agent for memory deficits in patients with PD receiving L-DOPA.
先前的研究表明，绞股蓝总皂苷（GPS）可改善1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）损伤的帕金森病（PD）大鼠模型中的焦虑症症状。本研究旨在探讨GPS对用左旋多巴（L-DOPA）治疗的MPTP损伤的PD小鼠模型记忆缺陷的影响。
用MPTP（30mg/kg/天，共5天）损伤的小鼠接受GPS（50mg/kg）和/或L-DOPA（10mg/kg和25mg/kg）治疗21天。在最后一次治疗后，使用被动回避和高架十字迷宫试验评估所有小鼠的行为变化。然后，我们评估了GPS治疗对酪氨酸羟化酶（TH）、多巴胺、N-甲基-D-天冬氨酸（NMDA）受体、细胞外信号调节激酶（ERK1/2）水平以及环磷酸腺苷反应元件结合蛋白（CREB）磷酸化的生化影响。
MPTP损伤的小鼠表现出与习惯学习和空间记忆相关的缺陷，用L-DOPA（25mg/kg）治疗会使这些缺陷进一步加重。然而，用GPS（50mg/kg）治疗可改善记忆缺陷。用GPS（50mg/kg）治疗还改善了用L-DOPA（25mg/kg）治疗的MPTP损伤引起的被动回避试验中记忆保持潜伏期的缩短，以及黑质和纹状体中TH免疫阳性细胞和多巴胺的水平。GPS治疗还减弱了高架十字迷宫试验中记忆转移潜伏期的增加和NMDA受体表达的增加，以及海马中ERK1/2和CREB磷酸化的减少。用L-DOPA（10mg/kg）治疗也改善了MPTP损伤小鼠的习惯学习和空间记忆缺陷，而用GPS（50mg/kg）治疗可进一步增强这种效果。
GPS通过调节在用L-DOPA治疗的MPTP损伤小鼠中的多巴胺能神经元和N-甲基-D-天冬氨酸受体介导的信号系统，改善习惯学习和空间记忆缺陷。GPS可能作为接受L-DOPA治疗的PD患者记忆缺陷的辅助治疗药物。
