title: Deficits in brain serotonin synthesis in a genetic mouse model of phenylketonuria.
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.
authors.affiliation: Department of Psychology, Universitá La Sapienza, Via dei Marsi 78, Rome 00185, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pascucci
authors.forename: Rossella
authors.initials: R
authors.lastname: Ventura
authors.forename: Stefano
authors.initials: S
authors.lastname: Puglisi-Allegra
authors.forename: Simona
authors.initials: S
authors.lastname: Cabib
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006720:Homozygote; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010661:Phenylketonurias / Q000235:genetics* / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan