Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice
Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice
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DOI：
10.1111/j.1471-4159.2007.05147.x
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发表时间：
2008-05-01
影响因子：
4.7
通讯作者：
Tanila, H.
中科院分区：
文献类型：
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作者：
Minkeviciene, R.;Ihalainen, J.;Tanila, H.
我们通过微透析评估了自由活动的携带突变人类淀粉样蛋白前体蛋白和早老素基因的年轻成年小鼠（7个月）和中年小鼠（17个月）及其野生型幼崽的基线和kcl刺激谷氨酸释放。此外，我们还评估了水迷宫中淀粉样蛋白病理和空间记忆受损的年龄相关发展以及谷氨酸转运体的变化。APdE9小鼠在6 ~ 15月龄表现出逐渐的空间记忆障碍。与7月龄APdE9小鼠相比，17月龄APdE9小鼠受刺激的谷氨酸释放明显下降。这种受刺激谷氨酸释放的年龄依赖性下降在野生型小鼠中也很明显，尽管它不像APdE9小鼠那样强劲。与个体基线相比，所有老年野生型小鼠在KCl刺激下谷氨酸释放增加25%或更多，但老年APdE9小鼠没有。VGLUT1水平有年龄依赖性下降，但VGLUT2、GLT-1和突触素水平没有下降。胶质酸性原纤维蛋白测定的中年APdE9小鼠星形胶质细胞活化增加。突触前谷氨酸反应减弱可能导致中年APdE9小鼠的记忆缺陷。
We assessed baseline and KCl-stimulated glutamate release by using microdialysis in freely moving young adult (7 months) and middle-aged (17 months) transgenic mice carrying mutated human amyloid precursor protein and presenilin genes (APdE9 mice) and their wild-type littermates. In addition, we assessed the age-related development of amyloid pathology and spatial memory impaired in the water maze and changes in glutamate transporters. APdE9 mice showed gradual spatial memory impairment between 6 and 15 months of age. The stimulated glutamate release declined very robustly in 17-month-old APdE9 mice as compared to 7-month-old APdE9 mice. This age-dependent decrease in stimulated glutamate release was also evident in wild-type mice, although it was not as robust as in APdE9 mice. When compared to individual baselines, all aged wild-type mice showed 25% or greater increase in glutamate release upon KCl stimulation, but none of the aged APdE9 mice. There was an age-dependent decline in VGLUT1 levels, but not in the levels of VGLUT2, GLT-1 or synaptophysin. Astrocyte activation as measured by glial acidic fibrillary protein was increased in middle-aged APdE9 mice. Blunted pre-synaptic glutamate response may contribute to memory deficit in middle-aged APdE9 mice.