胰淀素在痴呆小鼠和正常小鼠脑内的分布和表达变化

Distribution and expression of amylin in brain of Alzheimer's disease and normal mice

目的观察胰淀素在正常小鼠、阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠和肥胖模型小鼠脑内的分布和表达情况,分析其与小鼠脑内老年斑的关系,探讨胰淀素是否参与老年性痴呆的发病。方法取5月龄雄性APP/PS1双转基因小鼠(AD模型小鼠)、ob/ob肥胖模型小鼠及野生型小鼠(正常小鼠),采用免疫荧光染色方法检测胰淀素和老年斑在各组小鼠脑内的分布和表达。结果免疫荧光双标检测结果显示:胰淀素免疫阳性神经元广泛分布于APP/PS1双转基因小鼠脑内,包括皮质、海马、丘脑等区域,强阳性表达于岛叶和梨形皮质区域(P<0.01),而老年斑则选择性表达于新皮质、海马等区域,胰淀素的分布范围较老年斑的分布广泛,在部分老年斑的周围可见胰淀素免疫阳性物质分布。5月龄AD模型小鼠、ob/ob肥胖模型小鼠新皮质内胰淀素阳性神经元数目明显高于正常小鼠(P<0.05,P<0.01)。结论胰淀素在AD模型小鼠、ob/ob肥胖模型小鼠及正常小鼠脑内的分布和表达存在差异,这种差异有可能促进老年斑的形成以及参与AD疾病的发生。

Objective To determine the distribution and expression of amylin in the brain of Alzheimer＇s disease（ AD） model mice,ob/ob mice（ obese mice） and wild-type controls for the relationship between amylin and senile plaques,so as to investigate whether amylin is involved in the pathogenesis of senile dementia. Methods Five-month-old APP/PS1 double transgenic male mice（ AD model）,ob/ob mice and the wild-type mice were employed in this study. Immunofluorescence assay was used to detect the distribution and expression of amylin and senile plaques in the brain of 3 groups of mice. Results Amylin was widely distributed and expressed in the neurons throughout almost all the regions of brain in the APP/PS1 double transgenic mice,including the cerebral cortex,hippocampus,dorsal thalamus,and so on,with very high levels in the insular cortex and piriform cortex（ P〈0. 01）. While senile plaques were selectively distributed in the cerebral cortex and hippocampus. The distribution of amylin was much more extensive than that of senile plaques in the brain of the AD mice. Amylin positive substances were found gathering around the deposition of senile plaques. The number of amylin-positive neurons in the cerebral cortex was significantly higher in the AD and ob/ob mice than that the wild-type mice（ P〈0. 05,P〈0. 01）. Conclusion The distribution and expression of amylin are obviously different in the brain of the AD,ob/ob and wild-type mice,and these differences may promote the formation of senile plaques and be involved in the pathogenesis of AD.