Protein kinase C activity is associated with prefrontal cortical decline in aging
Protein kinase C activity is associated with prefrontal cortical decline in aging
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DOI：
10.1016/j.neurobiolaging.2007.08.020
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发表时间：
2009-05-01
影响因子：
4.2
通讯作者：
Arnsten, Amy F. T.
中科院分区：
文献类型：
--
作者：
Brennan, Avis R.;Yuan, Peixiong;Arnsten, Amy F. T.
衰老与前额皮质的缺陷有关，包括工作记忆障碍和神经元树突完整性受损。尽管蛋白激酶 C (PKC) 与结构可塑性有关，并且 PKC 的过度激活会导致幼年动物的工作记忆损伤，但 PKC 在老年人前额皮质损伤中的作用尚未得到研究。这项研究提供了第一个证据，证明 PKC 活性与衰老过程中的前额皮质功能障碍有关。用白屈菜红碱对 PKC 进行药理抑制可挽救老年大鼠的工作记忆损伤，并增强老年恒河猴的工作记忆。改善与年龄相关，年长的猴子在 PKC 抑制后表现出更大程度的改善。此外，前额皮质内的 PKC 活性与前额皮质神经元基底树突的长度以及老年大鼠的工作记忆表现呈负相关。这些发现共同表明 PKC 在老年动物中失调，并且 PKC 抑制剂可能有助于治疗老年人的认知缺陷。 (C) 2007 Elsevier Inc. 保留所有权利。
Aging is associated with deficiencies in the prefrontal cortex, including working memory impairment and compromised integrity of neuronal dendrites. Although protein kinase C (PKC) is implicated in structural plasticity, and overactivation of PKC results in working memory impairments in young animals, the role of PKC in prefrontal cortical impairments in the aged has not been examined. This study provides the first evidence that PKC activity is associated with prefrontal cortical dysfunction in aging. Pharmacological inhibition of PKC with chelerythrine rescued working memory impairments in aged rats and enhanced working memory in aged rhesus monkeys. Improvement correlated with age, with older monkeys demonstrating a greater degree of improvement following PKC inhibition. Furthermore, PKC activity within the prefrontal cortex was inversely correlated with the length of basal dendrites of prefrontal cortical neurons, as well as with working memory performance in aged rats. Together these findings indicate that PKC is dysregulated in aged animals and that PKC inhibitors may be useful in the treatment of cognitive deficits in the elderly. (C) 2007 Elsevier Inc. All rights reserved.