AUTHOR=Kang Shinwoo , Ha Sungji , Park Hyunjun , Nam Eunjoo , Suh Won Hyuk , Suh Yoo-Hun , Chang Keun-A 

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

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=Volume 12 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2018.00273

DOI=10.3389/fnbeh.2018.00273

ISSN=1662-5153

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