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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Deficits in brain serotonin synthesis in a genetic mouse model of phenylketonuria.

Although hyperphenylalaninemia causes neurological disturbances and mental retardation, the neuropathological effects of phenylalanine excess are still poorly understood. Brain serotonin depletion may play a major role in such disturbances and is a possible target for feasible pharmacotherapies. In the present study, we investigated hyperphenylalaninemia-related brain serotonin depletion using a genetic mouse model of phenylketonuria, the Pah(enu2) mutant. Mutant mice showed severe depletion of whole brain serotonin, a mild reduction in the brain level of tryptophan, its amino acid precursor, and major deficits in the brain level of 5-hydroxytryptophan, the second rate-limiting factor in serotonin synthesis. These results suggest that interference with brain 5-hydroxytryptophan synthesis may be the major cause of serotonin deficits in hyperphenylalaninemia.[1]


  1. Deficits in brain serotonin synthesis in a genetic mouse model of phenylketonuria. Pascucci, T., Ventura, R., Puglisi-Allegra, S., Cabib, S. Neuroreport (2002) [Pubmed]
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