Effect of cannabinoids HU-210 on senile plaques and learning and memory of APP/PS1 double transgenic mice

Abstract:

Objective：To examine whether HU-210 affects spatial learning and memory ability and senile plaques formation in APP/PS1 double transgenic mice. Methods：APP/PS1 double transgenic mice aged 3.5 months were randomly divided into HU-210 treated and saline-treated groups（n=10）. HU-210（100 μg/（kg·d）） and the same amount of saline were peritoneally injected into APP/PS1 mice for one month. Morris water maze and fear conditioning tests were used to assess the learning and memory abilities of animals.Immunohistochemical staining was applied to exam senile plaques in the brain of APP/PS1 mice. Results：The water maze test showed that HU-210-treated mice took shorter latency and swam a shorter distance to reach the platform than saline-treated controls. HU-210-treated mice had significantly more platform-passing times（5.40±1.52） in the correct quadrant of pool in the probe trial than that of controls（1.60±1.14，P<0.01）. Fear conditioning test showed that HU-210 mice had more freeze times（right after shock：38.30±15.16；24 h post-shock：99.89±5.71） than that of controls（right after shock：17.84±5.33；24 h post-shock：56.00±4.78，P<0.01） after electrical shock. Immunohistochemical staining showed that the number of senile plaques in the brain of HU-210-treated mice was notably decreased（control：3.90±2.51 vs.HU-210：9.70±5.67，P<0.05）. Conclusion：Treatment with HU-210 at early stage can significantly decrease senile plaques formation，which in turn improve the learning and memory abilities of APP/PS1 double transgenic mice.