Effects of phenylalanine on the survival and neurite outgrowth of rat cortical neurons in primary cultures: possible involvement of brain-derived neurotrophic factor.

Molecular and Cellular Biochemistry
Duan LiLili Liang

Abstract

Phenylketonuria (PKU) is characterized by elevated levels of phenylalanine (Phe) in plasma and cerebrospinal fluid of PKU patients, leading to mental retardation. The developmental delay in the cerebral cortex is one of the characteristic pathologic changes in untreated phenylketonuria patients. This is thought to be due to the toxic effects of Phe and/or its metabolites; however, the underlying mechanisms are as yet unknown. In this study, using a model system in which cultured cortical neurons were induced with Phe, we observed that Phe inhibited the longest neurite outgrowth and induced the neuronal death. We further demonstrated that the expression of BDNF mRNA and protein was significantly decreased by Phe, together with a decrease in extracellular signal-regulated kinase (ERK) and Akt phosphorylation activity. There was no change in expression of TrkB mRNA and protein. Considering the important role of BDNF in normal brain development and function, these L: -Phe-induced changes in BDNF in PKU brain may be a critical element of the neurological symptoms of PKU.

References

Jul 1, 1983·Early Human Development·M E CorderoV Aranda
Jul 1, 1996·Journal of Neuropathology and Experimental Neurology·C A DyerH L Levy
Jul 10, 1999·Neuron·H W HorchL C Katz
May 29, 2000·Brain Research·I FerrerT Ribalta
Oct 24, 2000·European Journal of Pediatrics·P R Huttenlocher
Jan 4, 2001·Trends in Neurosciences·A F Schinder, M Poo
May 9, 2002·Biochimica Et Biophysica Acta·Martine E Kienzle HagenCarlos S Dutra-Filho
Dec 25, 2002·Neuroreport·Tiziana PascucciSimona Cabib
Mar 20, 2003·Journal of Neuroscience Research·A V GlushakovA E Martynyuk
Apr 5, 2003·Annual Review of Biochemistry·Eric J Huang, Louis F Reichardt
Jun 7, 2003·Nature Cell Biology·Lindsey A AllanPaul R Clarke
May 20, 2004·The Journal of Biological Chemistry·John M SchmittThomas R Soderling
May 28, 2005·Metabolic Brain Disease·Huiwen Zhang, Xue Fan Gu
Sep 13, 2005·Molecular Genetics and Metabolism·A E MartynyukC N Seubert
Mar 22, 2006·Pediatric Research·Friederike HörsterStefan Kins
Apr 9, 2008·Pharmacology & Therapeutics·Margaret I Davis
Aug 19, 2008·Brain Research Reviews·Lucia Tapia-ArancibiaSandor Arancibia
Jun 6, 2009·Nature Reviews. Neurology·Chiara Zuccato, Elena Cattaneo

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Citations

Mar 7, 2020·Journal of Neuroscience Research·Bruna Klippel FerreiraPatricia Fernanda Schuck
Jan 10, 2017·Frontiers in Behavioral Neuroscience·Vibeke M BruinenbergEddy A van der Zee
Jun 5, 2018·Intractable & Rare Diseases Research·Zijuan QiJinxiang Han
Feb 14, 2021·Metabolic Brain Disease·Vanessa Trindade BortoluzziClovis Milton Duval Wannmacher

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