Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice.

Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice.
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DOI:
10.1002/ana.23793
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发表时间:
2013-02
影响因子:
11.2
通讯作者:
Gutmann, David H.
Gutmann, David H.
中科院分区:
医学1区
文献类型:
--
作者:
Diggs-Andrews, Kelly A.;Tokuda, Kazuhiro;Izumi, Yukitoshi;Zorumski, Charles F.;Wozniak, David F.;Gutmann, David H.

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患有 1 型神经纤维瘤病 (NF1) 的儿童容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、cAMP 和 Ras 稳态存在缺陷。通过行为学、电生理学和原代培养,我们现在证明多巴胺信号传导减少是神经元功能和学习中 cAMP 依赖性缺陷的原因。总的来说,这些结果表明多巴胺能功能缺陷是 NF1 儿童和成人空间学习和记忆受损的一个促成因素,并支持对特定个体使用恢复正常多巴胺稳态的治疗。
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, 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 one 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.
ERK信号传导的神经纤维素调节调节GABA释放和学习。
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