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.

Deficits in brain serotonin synthesis in a genetic mouse model of phenylketonuria / Pascucci, Tiziana; Ventura, Rossella; PUGLISI ALLEGRA, Stefano; Cabib, Simona. - In: NEUROREPORT. - ISSN 0959-4965. - 13:(2002), pp. 2561-2564. [10.1097/00001756-200212200-00036]

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

PASCUCCI, Tiziana;VENTURA, Rossella;PUGLISI ALLEGRA, Stefano;CABIB, Simona
2002

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.
2002
Amino acid deficency; Blood-brain barrier; Genetically modified animals; Inborn errors of metabolism; Neurotransmitter biosynthesis
01 Pubblicazione su rivista::01a Articolo in rivista
Deficits in brain serotonin synthesis in a genetic mouse model of phenylketonuria / Pascucci, Tiziana; Ventura, Rossella; PUGLISI ALLEGRA, Stefano; Cabib, Simona. - In: NEUROREPORT. - ISSN 0959-4965. - 13:(2002), pp. 2561-2564. [10.1097/00001756-200212200-00036]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/251148
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