正电子发射断层扫描（PET）成像在神经纤维瘤病-1 小鼠注意力缺陷临床前药物测试中的应用。
PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice.
机构信息
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
出版信息
Exp Neurol. 2011 Dec;232(2):333-8. doi: 10.1016/j.expneurol.2011.09.005. Epub 2011 Sep 22.
Abstract
Attention system abnormalities represent a significant barrier to scholastic achievement in children with neurofibromatosis-1 (NF1). Using a novel mouse model of NF1-associated attention deficit (ADD), we demonstrate a presynaptic defect in striatal dopaminergic homeostasis and leverage this finding to apply [(11)C]-raclopride positron-emission tomography (PET) in the intact animal. While methylphenidate and l-Deprenyl correct both striatal dopamine levels on PET imaging and defective attention system function in Nf1 mutant mice, pharmacologic agents that target de-regulated cyclic AMP and RAS signaling in these mice do not. These studies establish a robust preclinical model to evaluate promising agents for NF1-associated ADD.
摘要
注意系统异常是神经纤维瘤病 1 型（NF1）患儿学业成就的重大障碍。我们使用一种新型 NF1 相关注意缺陷（ADD）的小鼠模型，证明了纹状体多巴胺能稳态的突触前缺陷，并利用这一发现对完整动物进行 [(11)C]-raclopride 正电子发射断层扫描（PET）。虽然哌甲酯和 l-Deprenyl 均可纠正 PET 成像中的纹状多巴胺水平和 Nf1 突变小鼠的注意力系统功能缺陷，但针对这些小鼠中失调的环 AMP 和 RAS 信号的药物却不能。这些研究建立了一个强大的临床前模型，用于评估 NF1 相关 ADD 的有前途的药物。
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