Loss of asymmetric spine synapses in prefrontal cortex of motor-asymptomatic, dopamine-depleted, cognitively impaired MPTP-treated monkeys.
Loss of asymmetric spine synapses in prefrontal cortex of motor-asymptomatic, dopamine-depleted, cognitively impaired MPTP-treated monkeys.
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DOI：
10.1017/s1461145712000892
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发表时间：
2013-05
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影响因子：
--
通讯作者：
Roth RH
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作者：
Elsworth JD;Leranth C;Redmond DE Jr;Roth RH
帕金森病通常被描述为运动障碍;然而，在大多数患者中，依赖于前额叶皮质的认知能力在疾病的早期阶段下降。帕金森氏病认知缺陷的基础变化还没有得到很好的理解。我们假设，减少多巴胺信号在前额叶皮层帕金森氏病是一个预兆，有害的突触变化的锥体神经元在前额叶皮层的功能是必要的正常认知。我们以前的数据表明，猴子暴露于神经毒素，MPTP，但没有表现出明显的运动缺陷（运动无症状），表现出认知缺陷，在前额叶皮层依赖的任务。本研究结果表明，电机无症状MPTP治疗的猴子有一个减少多巴胺浓度和一个显着较低的数量（50%）的不对称（兴奋性）脊突触在层II/III，但不是层V，背外侧前额叶皮层，与对照组相比。与此相反，无论是多巴胺的浓度，也不对称突触数量的改变，在内嗅皮层的MPTP治疗的猴子。总之，这些研究结果表明，在前额叶皮层的树突上的不对称的棘突触的数量是多巴胺依赖性的，突触的损失可能是一个形态学基板的认知功能障碍引起的多巴胺神经传递减少在这个地区。调节前额叶皮层中不对称的棘突触数量代表了多巴胺的一种新的神经可塑性功能。
Parkinson's disease is usually characterized as a movement disorder; however cognitive abilities that are dependent on the prefrontal cortex decline at an early stage of the disease in most patients. The changes that underlie cognitive deficits in Parkinson’s disease are not well understood. We hypothesize that reduced dopamine signaling in the prefrontal cortex in Parkinson’s disease is a harbinger of detrimental synaptic changes in pyramidal neurons in the prefrontal cortex whose function is necessary for normal cognition. Our previous data showed that monkeys exposed to the neurotoxin, MPTP, but not exhibiting overt motor deficits (motor-asymptomatic), displayed cognitive deficits in prefrontal cortex-dependent tasks. The present results demonstrate that motor-asymptomatic MPTP-treated monkeys have a reduced dopamine concentration and a substantially lower number (50%) of asymmetric (excitatory) spine synapses in layer II/III, but not layer V, of the dorsolateral prefrontal cortex, compared with controls. In contrast, neither dopamine concentration nor asymmetric synapse number was altered in the entorhinal cortex of MPTP-treated monkeys. Together these findings suggest that the number of asymmetric spine synapses on dendrites in the prefrontal cortex is dopamine-dependent and that the loss of synapses may be a morphological substrate of the cognitive deficits induced by a reduction in dopamine neurotransmission in this region. Modulation of asymmetric spine synapse number in prefrontal cortex represents a novel neuroplastic function for dopamine.