Cognitive Decline Is Associated with Reduced Reelin Expression in the Entorhinal Cortex of Aged Rats
Cognitive Decline Is Associated with Reduced Reelin Expression in the Entorhinal Cortex of Aged Rats
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DOI：
10.1093/cercor/bhq106
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发表时间：
2011-02-01
期刊：
影响因子：
3.7
通讯作者：
Gallagher, Michela
中科院分区：
文献类型：
--
作者：
Stranahan, Alexis M.;Haberman, Rebecca P.;Gallagher, Michela
大脑区域和神经回路对衰老期间和与年龄相关的神经退行性疾病发生的变化的脆弱性不同。在包括内侧颞叶记忆系统的区域中，内嗅皮层的第II层神经元（其形成对海马结构的穿通路径输入）在衰老过程中表现出早期改变。内嗅皮层第II层神经元表达与突触可塑性有关的糖蛋白Reelin。在这里，我们报告说，年龄相关的减少reelin表达的内嗅皮层与认知能力下降。使用免疫组织化学和原位杂交，我们观察到的数量减少的reelin免疫反应细胞和reelin信使RNA的表达在外侧内嗅皮层的老年大鼠的认知功能受损相对于年轻的成年人和老年大鼠保留的认知能力。认知障碍老年大鼠的外侧内嗅皮层也表现出其他分子标志物的变化，包括磷酸化tau蛋白的积累增加和突触素免疫反应性降低。两者合计，这些研究结果表明，减少reelin的表达，从第二层内嗅神经元，可能有助于网络功能障碍，发生在记忆丧失的老化。
Brain regions and neural circuits differ in their vulnerability to changes that occur during aging and in age-related neurodegenerative diseases. Among the areas that comprise the medial temporal lobe memory system, the layer II neurons of the entorhinal cortex, which form the perforant path input to the hippocampal formation, exhibit early alterations over the course of aging Reelin, a glycoprotein implicated in synaptic plasticity, is expressed by entorhinal cortical layer II neurons. Here, we report that an age-related reduction in reelin expression in the entorhinal cortex is associated with cognitive decline. Using immunohistochemistry and in situ hybridization, we observed decreases in the number of Reelin-immunoreactive cells and reelin messenger RNA expression in the lateral entorhinal cortex of aged rats that are cognitively impaired relative to young adults and aged rats with preserved cognitive abilities. The lateral entorhinal cortex of aged rats with cognitive impairment also exhibited changes in other molecular markers, including increased accumulation of phosphorylated tau and decreased synaptophysin immunoreactivity. Taken together, these findings suggest that reduced reelin expression, emanating from layer II entorhinal neurons, may contribute to network dysfunction that occurs during memory loss in aging.