Light shed on the cause of the most common learning disability

September, 2010

The discovery that the mutated NF1 gene inhibits working memory through too much GABA in the prefrontal cortex offers hope for an effective therapy for those with the most common learning disability.

Neurofibromatosis type 1 (NF1) is the most common cause of learning disabilities, caused by a mutation in a gene that makes a protein called neurofibromin. Mouse research has now revealed that these mutations are associated with higher levels of the inhibitory neurotransmitter GABA in the medial prefrontal cortex. Brain imaging in humans with NF1 similarly showed reduced activity in the prefrontal cortex when performing a working memory task, with the levels of activity correlating with task performance. It seems, therefore, that this type of learning disability is a result of too much GABA in the prefrontal cortex inhibiting the activity of working memory. Potentially they could be corrected with a drug that normalizes the excess GABA's effect. The researchers are currently studying the effect of the drug lovastatin on NF1 patients.

Reference: 

[1688] Shilyansky, C., Karlsgodt K. H., Cummings D. M., Sidiropoulou K., Hardt M., James A. S., et al.
(2010).  Neurofibromin regulates corticostriatal inhibitory networks during working memory performance.
Proceedings of the National Academy of Sciences. 107(29), 13141 - 13146.

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