Abstract | OBJECTIVE:
Phenylketonuria (PKU) is an inherited metabolic disease characterized by plasma hyperphenylalaninemia and several neurological symptoms that can be controlled by rigorous dietetic treatment. The cellular mechanisms underlying impaired brain functions are still unclear. It has been proposed, however, that phenylalanine interference in cognitive functions depends on impaired dopamine (DA) transmission in the prefrontal cortical area due to reduced availability of the precursor tyrosine. Here, using Pah(enu2) (ENU2) mice, the genetic murine model of PKU, we investigated all metabolic steps of catecholamine neurotransmission within the medial preFrontal Cortex (mpFC), availability of the precursor tyrosine, synthesis and release, to find an easy way to reinstate normal cortical DA neurotransmission. METHODS AND RESULTS: CONCLUSION: The data suggests that a strategy of using tyrosine supplementation to treat PKU is unlikely to be effective, whereas small dose L-DOPA administration is likely to have a positive therapeutic effect.
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Authors | Tiziana Pascucci, Giacomo Giacovazzo, Diego Andolina, David Conversi, Fabio Cruciani, Simona Cabib, Stefano Puglisi-Allegra |
Journal | Journal of inherited metabolic disease
(J Inherit Metab Dis)
Vol. 35
Issue 6
Pg. 1001-9
(Nov 2012)
ISSN: 1573-2665 [Electronic] United States |
PMID | 22447154
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Catecholamines
- Tyrosine
- Levodopa
- Phenylalanine Hydroxylase
- Tyrosine 3-Monooxygenase
- Dopamine
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Topics |
- Animals
- Catecholamines
(metabolism)
- Disease Models, Animal
- Dopamine
(metabolism)
- Levodopa
(administration & dosage)
- Male
- Mice
- Mice, Mutant Strains
- Phenylalanine Hydroxylase
(genetics)
- Phenylketonurias
(blood, drug therapy, genetics, metabolism)
- Prefrontal Cortex
(metabolism)
- Synaptic Transmission
(drug effects)
- Tyrosine
(administration & dosage, blood, metabolism)
- Tyrosine 3-Monooxygenase
(deficiency)
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