Departments of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Ann Neurol. 2013 Feb;73(2):309-15. doi: 10.1002/ana.23793. Epub 2012 Dec 7.
Children with neurofibromatosis type 1 (NF1) are prone to learning and behavioral abnormalities, including problems with spatial learning and attention. The molecular etiology for these deficits is unclear, as previous studies have implicated defective dopamine, cyclic adenosine monophosphate (cAMP), and Ras homeostasis. Using behavioral, electrophysiological, and primary culture, we now demonstrate that reduced dopamine signaling is responsible for cAMP-dependent defects in neuron function and learning. Collectively, these results establish defective dopaminergic function as a contributing factor underlying impaired spatial learning and memory in children and adults with NF1, and support the use of treatments that restore normal dopamine homeostasis for select individuals.
患有神经纤维瘤病 1 型（NF1）的儿童易出现学习和行为异常，包括空间学习和注意力问题。这些缺陷的分子病因尚不清楚，因为之前的研究表明多巴胺、环腺苷酸（cAMP）和 Ras 动态平衡存在缺陷。我们现在通过行为、电生理和原代培养研究证明，多巴胺信号的减少导致 cAMP 依赖性神经元功能和学习缺陷。总的来说，这些结果表明，多巴胺能功能缺陷是导致 NF1 儿童和成人空间学习和记忆受损的一个因素，并支持使用恢复正常多巴胺动态平衡的治疗方法来治疗特定个体。
