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

Tiziana Pascucci, Rossella Ventura, Stefano Puglisi-Allegra, Simona Cabib

Research output: Contribution to journalArticlepeer-review


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 Pahenu2 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.

Original languageEnglish
Pages (from-to)2561-2564
Number of pages4
Issue number18
Publication statusPublished - Dec 20 2002


  • Amino acid deficency
  • Blood-brain barrier
  • Genetically modifed animals
  • Inborn errors of metabolism
  • Neurotransmitter biosynthesis

ASJC Scopus subject areas

  • Neuroscience(all)

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