Adrenocortical Status Predicts the Degree of Age-Related Deficits in Prefrontal Structural Plasticity and Working Memory
Adrenocortical Status Predicts the Degree of Age-Related Deficits in Prefrontal Structural Plasticity and Working Memory
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DOI：
10.1523/jneurosci.1385-14.2014
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发表时间：
2014-06-18
影响因子：
5.3
通讯作者：
Radley, Jason J.
中科院分区：
文献类型：
--
作者：
Anderson, Rachel M.;Birnie, Andrew K.;Radley, Jason J.
衰老中的认知能力下降具有相当大的变异性，一些人经历了显著的损伤，而另一些人则保持了完整的功能。尽管先前的研究将下丘脑-垂体-肾上腺（HPA）轴活动升高与衰老过程中海马功能受损联系起来，但这种差异是否可能导致其他认知功能恶化的想法已经消失。在这里，我们调查是否内源性差异HPA活性预测与年龄相关的损伤，前额叶结构和行为的可塑性。年轻和年老的大鼠（4和21个月，分别）被划分为低或高HPA活性，根据平均值的皮质酮释放从每只动物在24小时内重复采样。选择内侧前额叶皮质边缘区的锥体神经元进行细胞内染料填充，然后进行3D成像和树突棘形态计量学分析。老年动物表现出树突棘丢失和几何特征改变;然而，这些减少主要是由于皮质酮升高的亚组。此外，高肾上腺皮质活动在老龄化与脊柱头直径和长度的频率分布的下移，而老年动物低皮质酮显示这些指标的上移。后续的行为实验表明，与年龄相关的空间工作记忆缺陷加剧了HPA活性的增加。相比之下，年轻动物中HPA活性的变化未能影响结构或行为可塑性。这些数据表明，糖皮质激素的累积暴露是年龄相关的前额叶损伤的一个中心基础过程，并定义了与年龄相关的认知功能不同轨迹的突触特征。
Cognitive decline in aging is marked by considerable variability, with some individuals experiencing significant impairments and others retaining intact functioning. Whereas previous studies have linked elevated hypothalamo-pituitary-adrenal (HPA) axis activity with impaired hippocampal function during aging, the idea has languished regarding whether such differences may underlie the deterioration of other cognitive functions. Here we investigate whether endogenous differences in HPA activity are predictive of age-related impairments in prefrontal structural and behavioral plasticity. Young and aged rats (4 and 21 months, respectively) were partitioned into low or high HPA activity, based upon averaged values of corticosterone release from each animal obtained from repeated sampling across a 24 h period. Pyramidal neurons in the prelimbic area of medial prefrontal cortex were selected for intracellular dye filling, followed by 3D imaging and analysis of dendritic spine morphometry. Aged animals displayed dendritic spine loss and altered geometric characteristics; however, these decrements were largely accounted for by the subgroup bearing elevated corticosterone. Moreover, high adrenocortical activity in aging was associated with downward shifts in frequency distributions for spine head diameter and length, whereas aged animals with low corticosterone showed an upward shift in these indices. Follow-up behavioral experiments revealed that age-related spatial working memory deficits were exacerbated by increased HPA activity. By contrast, variations in HPA activity in young animals failed to impact structural or behavioral plasticity. These data implicate the cumulative exposure to glucocorticoids as a central underlying process in age-related prefrontal impairment and define synaptic features accounting for different trajectories in age-related cognitive function.