大麻素HU-210对APP/PS转基因小鼠学习记忆及脑内老年斑的影响

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

摘要:

目的：研究大麻素HU-210对APP/PS转基因小鼠空间学习记忆能力和脑组织中老年斑表达变化的影响。方法：3.5月龄APP/PS转基因小鼠随机分为HU-210处理组和生理盐水对照组，每组10只，用大麻素HU-210[100 μg/（kg·次）]和等量生理盐水分别腹腔注射1个月。应用Morris水迷宫和恐惧实验检测各组小鼠学习记忆能力的变化；采用免疫组化染色以观察小鼠脑内老年斑的变化。结果：水迷宫实验显示，与对照组相比，HU-210处理组小鼠找到平台的潜伏期及搜索路程显著缩短；HU-210处理组小鼠穿越平台次数（5.40±1.52）明显高于对照组小鼠（1.60±1.14，P<0.01）；恐惧实验显示，电击后HU-210处理组小鼠出现Freeze次数（电击后即刻：38.30±15.16；电击后24 h：99.89±5.71）明显高于生理盐水对照组（电击后即刻：17.84±5.33；电击后24 h：56.00±4.78，P<0.01）。免疫组化显示，与对照组（3.90±2.51）相比，HU-210处理组小鼠脑内老年斑数量（9.70±5.67）明显减少（P<0.05）。结论：在老年斑形成初期使用大麻素可明显减少痴呆模型小鼠脑内老年斑的形成，从而改善痴呆模型小鼠的认知功能。

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.