Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.

Hyperphenylalaninemia (HPA) refers to all clinical conditions characterized by increased amounts of phenylalanine (PHE) in blood and other tissues. According to their blood PHE concentrations under a free diet, hyperphenylalaninemic patients are commonly classified into phenotypic subtypes: classica...

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Autores principales:	Tiziana Pascucci, Giacomo Giacovazzo, Diego Andolina, Alessandra Accoto, Elena Fiori, Rossella Ventura, Cristina Orsini, David Conversi, Claudia Carducci, Vincenzo Leuzzi, Stefano Puglisi-Allegra
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/196aa9ef15e14892ba96011e366856e9
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spelling	oai:doaj.org-article:196aa9ef15e14892ba96011e366856e92021-11-18T08:40:47ZBehavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.1932-620310.1371/journal.pone.0084697https://doaj.org/article/196aa9ef15e14892ba96011e366856e92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376837/?tool=EBIhttps://doaj.org/toc/1932-6203Hyperphenylalaninemia (HPA) refers to all clinical conditions characterized by increased amounts of phenylalanine (PHE) in blood and other tissues. According to their blood PHE concentrations under a free diet, hyperphenylalaninemic patients are commonly classified into phenotypic subtypes: classical phenylketonuria (PKU) (PHE > 1200 µM/L), mild PKU (PHE 600-1200 µM/L) and persistent HPA (PHE 120-600 µM/L) (normal blood PHE < 120 µM/L). The current treatment for hyperphenylalaninemic patients is aimed to keep blood PHE levels within the safe range of 120-360 µM/L through a PHE-restricted diet, difficult to achieve. If untreated, classical PKU presents variable neurological and mental impairment. However, even mildly elevated blood PHE levels, due to a bad compliance to dietary treatment, produce cognitive deficits involving the prefrontal cortical areas, extremely sensible to PHE-induced disturbances. The development of animal models of different degrees of HPA is a useful tool for identifying the metabolic mechanisms underlying cognitive deficits induced by PHE. In this paper we analyzed the behavioral and biochemical phenotypes of different forms of HPA (control, mild-HPA, mild-PKU and classic-PKU), developed on the base of plasma PHE concentrations. Our results demonstrated that mice with different forms of HPA present different phenotypes, characterized by increasing severity of behavioral symptoms and brain aminergic deficits moving from mild HPA to classical PKU forms. In addition, our data identify preFrontal cortex and amygdala as the most affected brain areas and confirm the highest susceptibility of brain serotonin metabolism to mildly elevated blood PHE.Tiziana PascucciGiacomo GiacovazzoDiego AndolinaAlessandra AccotoElena FioriRossella VenturaCristina OrsiniDavid ConversiClaudia CarducciVincenzo LeuzziStefano Puglisi-AllegraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84697 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiziana Pascucci Giacomo Giacovazzo Diego Andolina Alessandra Accoto Elena Fiori Rossella Ventura Cristina Orsini David Conversi Claudia Carducci Vincenzo Leuzzi Stefano Puglisi-Allegra Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.
description	Hyperphenylalaninemia (HPA) refers to all clinical conditions characterized by increased amounts of phenylalanine (PHE) in blood and other tissues. According to their blood PHE concentrations under a free diet, hyperphenylalaninemic patients are commonly classified into phenotypic subtypes: classical phenylketonuria (PKU) (PHE > 1200 µM/L), mild PKU (PHE 600-1200 µM/L) and persistent HPA (PHE 120-600 µM/L) (normal blood PHE < 120 µM/L). The current treatment for hyperphenylalaninemic patients is aimed to keep blood PHE levels within the safe range of 120-360 µM/L through a PHE-restricted diet, difficult to achieve. If untreated, classical PKU presents variable neurological and mental impairment. However, even mildly elevated blood PHE levels, due to a bad compliance to dietary treatment, produce cognitive deficits involving the prefrontal cortical areas, extremely sensible to PHE-induced disturbances. The development of animal models of different degrees of HPA is a useful tool for identifying the metabolic mechanisms underlying cognitive deficits induced by PHE. In this paper we analyzed the behavioral and biochemical phenotypes of different forms of HPA (control, mild-HPA, mild-PKU and classic-PKU), developed on the base of plasma PHE concentrations. Our results demonstrated that mice with different forms of HPA present different phenotypes, characterized by increasing severity of behavioral symptoms and brain aminergic deficits moving from mild HPA to classical PKU forms. In addition, our data identify preFrontal cortex and amygdala as the most affected brain areas and confirm the highest susceptibility of brain serotonin metabolism to mildly elevated blood PHE.
format	article
author	Tiziana Pascucci Giacomo Giacovazzo Diego Andolina Alessandra Accoto Elena Fiori Rossella Ventura Cristina Orsini David Conversi Claudia Carducci Vincenzo Leuzzi Stefano Puglisi-Allegra
author_facet	Tiziana Pascucci Giacomo Giacovazzo Diego Andolina Alessandra Accoto Elena Fiori Rossella Ventura Cristina Orsini David Conversi Claudia Carducci Vincenzo Leuzzi Stefano Puglisi-Allegra
author_sort	Tiziana Pascucci
title	Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.
title_short	Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.
title_full	Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.
title_fullStr	Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.
title_full_unstemmed	Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.
title_sort	behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/196aa9ef15e14892ba96011e366856e9
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Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.

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