Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys.
Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys.
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DOI：
10.1017/s1461145711000939
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Roth RH
中科院分区：
文献类型：
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作者：
Elsworth JD;Hajszan T;Leranth C;Roth RH
精神分裂症患者、长期滥用苯环己哌啶（PCP）的人和接受PCP治疗的猴子都表现出持久的认知缺陷。有证据表明，前额叶皮层脊突触的损失导致认知功能障碍，这表明在猴PCP模型中存在突触病理学;然而，没有这种变化的直接证据。在这里，我们使用猴子PCP模型的精神分裂症，以调查在超微结构水平是否重建背外侧前额叶皮层（DLPFC）不对称的脊柱突触发生后PCP。亚慢性PCP治疗导致不对称的脊柱突触的数量减少，这是更大的DLPFC的第II/III层比V，与车辆处理的控制。这种减少可能有助于PCP诱导的认知功能障碍的非人灵长类动物模型，也许在精神分裂症。因此，PCP模型中的突触丢失为开发该模型和精神分裂症中认知功能障碍的潜在治疗提供了新的靶点。
Schizophrenic patients, long-term abusers of phencyclidine (PCP), and monkeys treated with PCP all exhibit enduring cognitive deficits. Evidence indicates that loss of prefrontal cortex spine synapses results in cognitive dysfunction, suggesting the presence of synaptic pathology in the monkey PCP model; however, there is no direct evidence of such changes. Here we use the monkey PCP model of schizophrenia to investigate at the ultrastructural level whether remodeling of dorsolateral prefrontal cortex (DLPFC) asymmetric spine synapses occurs following PCP. Subchronic PCP treatment resulted in a decrease in the number of asymmetric spine synapses, which was greater in layer II/III than V of DLPFC, compared to vehicle-treated controls. This decrease may contribute to PCP-induced cognitive dysfunction in the nonhuman primate model and perhaps in schizophrenia. Thus, the synapse loss in the PCP model provides a novel target for the development of potential treatments of cognitive dysfunction in this model and in schizophrenia.