Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex
Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex
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DOI：
10.1073/pnas.0704757104
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发表时间：
2007-07-03
影响因子：
11.1
通讯作者：
Morrison, John H.
中科院分区：
文献类型：
--
作者：
Hao, Jiandong;Rapp, Peter R.;Morrison, John H.
我们之前报道过，长期循环雌激素(E)治疗逆转了卵巢切除（OVX）雌性恒河猴中由胼胝体前额叶皮质（cdIPFC）介导的年龄相关的认知功能损伤，并且E诱导第三层dPFC锥体神经元的脊柱密度相应增加。我们现在研究了同样的E治疗对年轻成年女性的影响。与老龄猴子的结果相反，相对于载体控制值（年轻OVX+Veh组），E治疗未能提高dipfc依赖的任务表现，但仍导致脊柱密度显著增加。然而，这种反应伴随着树突长度的下降，因此在年轻的OVX+Veh组和OVX+E组中，每个神经元的棘总数是相等的。实足年龄的强大影响，独立于卵巢激素状态，也被观察到，包括显著的年龄相关的树突长度和脊柱密度的下降，在老年人中，小的脊柱优先减少。值得注意的是，尽管年轻的OVX+Veh猴子的小脊柱补体仍高于服用E的老年猴子，但循环E对脊柱的影响部分逆转。综上所述，在年轻和年老的猴子中，dPFC中的第三层锥体神经元对卵巢激素状态都很敏感，但这些影响在不同年龄组中并不完全相同。结果还表明，E治疗对老年猴子的认知益处是通过灵长类dIPFC中小的、高度塑性的树突棘的周期性增加来实现突触可塑性的。
We previously reported that long-term cyclic estrogen (E) treatment reverses age-related impairment of cognitive function mediated by the clorsolateral prefrontal cortex (cdIPFC) in ovariectomized (OVX) female rhesus monkeys, and that E induces a corresponding increase in spine density in layer III dPFC pyramidal neurons. We have now investigated the effects of the same E treatment in young adult females. In contrast to the results for aged monkeys, E treatment failed to enhance dIPFC-dependent task performance relative to vehicle control values (group young OVX+Veh) but nonetheless led to a robust increase in spine density. This response was accompanied by a decline in dendritic length, however, such that the total number of spines per neuron was equivalent in young OVX+Veh and OVX+E groups. Robust effects of chronological age, independent of ovarian hormone status, were also observed, comprising significant age-related declines in dendritic length and spine density, with a preferential decrease in small spines in the aged groups. Notably, the spine effects were partially reversed by cyclic E administration, although young OVX+Veh monkeys still had a higher complement of small spines than did aged E treated monkeys. In summary, layer III pyramidal neurons in the dPFC are sensitive to ovarian hormone status in both young and aged monkeys, but these effects are not entirely equivalent across age groups. The results also suggest that the cognitive benefit of E treatment in aged monkeys is mediated by enabling synaptic plasticity through a cyclical increase in small, highly plastic dendritic spines in the primate dIPFC.