PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice
PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice
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DOI：
10.1016/j.expneurol.2011.09.005
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发表时间：
2011-12-01
影响因子：
5.3
通讯作者：
Gutmann, David H.
中科院分区：
文献类型：
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作者：
Brown, Jacquelyn A.;Xu, Jinbin;Gutmann, David H.
注意力系统异常是神经纤维瘤病-1（NF 1）患儿学习成绩的重要障碍。使用一种新的NF 1相关注意力缺陷（ADD）小鼠模型，我们证明了纹状体多巴胺能稳态的突触前缺陷，并利用这一发现在完整动物中应用[（11）C]-雷氯必利正电子发射断层扫描（PET）。虽然哌甲酯和L-丙炔苯丙胺纠正了Nf 1突变小鼠PET成像上的纹状体多巴胺水平和缺陷的注意力系统功能，但靶向这些小鼠中失调的环AMP和RAS信号传导的药理学药物却没有。这些研究建立了一个强大的临床前模型，以评估有前途的药物治疗NF 1相关ADD。（C）2011 Elsevier Inc. All rights reserved.
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. (C) 2011 Elsevier Inc. All rights reserved.