Apical vulnerability to dendritic retraction in prefrontal neurones of ageing SAMP10 mouse: a model of cerebral degeneration
Apical vulnerability to dendritic retraction in prefrontal neurones of ageing SAMP10 mouse: a model of cerebral degeneration
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DOI：
10.1111/j.1365-2990.2006.00632.x
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发表时间：
2006-02
影响因子：
5
通讯作者：
A. Shimada;M. Tsuzuki;H. Keino;M. Satoh;Y. Chiba;Y. Saitoh;M. Hosokawa
中科院分区：
文献类型：
--
作者：
A. Shimada;M. Tsuzuki;H. Keino;M. Satoh;Y. Chiba;Y. Saitoh;M. Hosokawa
SAMP10小鼠是加速衰老模型，其中衰老的特征是与年龄相关的大脑皮层和边缘结构萎缩、学习和记忆任务表现不佳、抑郁行为以及胆碱能和多巴胺能改变。在这里，我们使用定量高尔基体方法研究了 SAMP10 小鼠内侧前额皮质锥体细胞的树突状乔木和棘密度与年龄相关的变化。随着年龄的增长，前额叶神经元的树突逐渐向躯体收缩，整体复杂性相对保持。顶端树突比基部树突受到的影响要严重得多。与 3 个月大的小鼠相比，12 个月大的小鼠顶树突的总长度和脊柱密度分别减少了 45% 和 55%。免疫组织化学和免疫印迹分析表明，微管相关蛋白（MAP）2（树突标记物）的表达不仅在前皮质中，而且在 SAMP10 小鼠的后皮质和嗅觉结构中以与年龄相关的方式下降。 MAP2 mRNA 表达的减少导致 MAP2 蛋白表达的减少。这些结果表明，顶端树突的回缩，而不是基底树突的回缩，以及前额神经元中棘的丢失，似乎是导致老年 SAMP10 小鼠学习和记忆性能较差的原因。还表明与年龄相关的树突回缩发生在广泛的区域，包括整个大脑皮层和嗅觉结构。
The SAMP10 mouse is a model of accelerated ageing in which senescence is characterized by age‐related atrophy of the cerebral cortex and limbic structures, poor learning and memory task performance with depressive behaviour and cholinergic and dopaminergic alterations. Here we studied age‐related changes in the dendritic arbors and spine density of pyramidal cells in the medial prefrontal cortex of SAMP10 mice using a quantitative Golgi method. Dendrites of prefrontal neurones gradually retracted with ageing towards the soma with the relative preservation of overall complexity. Apical dendrites were much more severely affected than basal dendrites. The combined length of the apical dendrites and spine density were decreased by 45% and 55%, respectively, in mice at 12 months, compared with mice at 3 months of age. Immunohistochemical and immunoblot analyses indicated that expression of microtubule‐associated protein (MAP) 2, a marker of dendrites, decreased in an age‐related manner not only in the anterior cortex but also in the posterior cortex and olfactory structures in SAMP10 mice. Decreased expression of MAP2 mRNA caused the decrease in MAP2 protein expression. These results suggest that retraction of apical, but not of basal dendrites, with a loss of spines in prefrontal neurones, appears to be responsible for poor learning and memory performance in aged SAMP10 mice. It is also suggested that age‐related dendritic retraction occurs in a wide area including the entire cerebral cortex and olfactory structures.