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Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice.


ABSTRACT: 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.

SUBMITTER: Diggs-Andrews KA 

PROVIDER: S-EPMC3608728 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice.

Diggs-Andrews Kelly A KA   Tokuda Kazuhiro K   Izumi Yukitoshi Y   Zorumski Charles F CF   Wozniak David F DF   Gutmann David H DH  

Annals of neurology 20121207 2


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  ...[more]

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