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Neuroreport. 2002 Dec 20;13(18):2561-4.

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

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  • 1Department of Psychology, Universitá La Sapienza, Via dei Marsi 78, Rome 00185, Italy.

Abstract

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.

PMID:
12499868
[PubMed - indexed for MEDLINE]
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