Clinical Neuroscience And NeuropathologyDeficits in brain serotonin synthesis in a genetic mouse model of phenylketonuriaPascucci, Tiziana1 2; Ventura, Rossella1 2; Puglisi-Allegra, Stefano1 2; Cabib, Simona1 2 3 CA Author Information 1Department of Psychology, Universitá La Sapienza, Via dei Marsi 78, Roma 00185 2IRCCS Fondazione Santa Lucia, Rome 3Istituto di Psicobiologia e Psicofarmacologia (CNR), Rome, Italy CA,1Corresponding Author and Address: [email protected] Received 3 July 2002; accepted 18 July 2002 NeuroReport: December 20, 2002 - Volume 13 - Issue 18 - p 2561-2564 Buy 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 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. © 2002 Lippincott Williams & Wilkins, Inc.