Effects of a Dehydroevodiamine-Derivative on Synaptic Destabilization and Memory Impairment in the 5xFAD, Alzheimer's Disease Mouse Model

Frontiers in Behavioral Neuroscience

Won Hyuk Suh¹  Hyunjun Park²  Keun-A Chang²  Yoo-Hun Suh⁴  Eunjoo Nam⁴  Shinwoo Kang⁴  Sungji Ha⁴ 

[1] Department of Bioengineering, College of Engineering, Temple UniversityPhiladelphia, PA, United States;Department of Health Sciences and Technology, GAIHSTGachon University, Incheon, South Korea;Department of Pharmacology, College of MedicineGachon University, Incheon, South Korea;Neuroscience Research InstituteGachon University, Incheon, South Korea;

关键词: Alzheimer's disease;    carboxy-dehydroevodiamine;    memory impairment;    5xFAD;    synaptic destabilization;   

DOI  :  10.3389/fnbeh.2018.00273

来源: DOAJ

【 摘 要 】

Carboxy-dehydroevodiamine·HCl (cx-DHED) is a derivative of DHED, which improves memory impairment. Carboxyl modification increases solubility in water, indicating that its bioavailability is higher than that of DHED. Cx-DHED is expected to have better therapeutic effects on Alzheimer's disease (AD) than DHED. In this study, we investigated the therapeutic effects of cx-DHED and the underlying mechanism in 5xFAD mice, transgenic (Tg) mouse model of AD model mice. In several behavioral tests, such as Y-maze, passive avoidance, and Morris water maze test, memory deficits improved significantly in cx-DHED-treated transgenic (Tg) mice compared with vehicle-treated Tg mice. We also found that AD-related pathologies, including amyloid plaque deposition and tau phosphorylation, were reduced after the treatment of Tg mice with cx-DHED. We determined the levels of synaptic proteins, such as GluN1, GluN2A, GluN2B, PSD-95 and Rabphilin3A, and Rab3A in the brains of mice of each group and found that GluN2A and PSD-95 were significantly increased in the brains of cx-DHED-treated Tg mice when compared with the brains of Tg-vehicle mice. These results suggest that cx-DHED has therapeutic effects on 5xFAD, AD model mice through the improvement of synaptic stabilization.

【 授权许可】

Unknown