Linked Life Data

16549526

Source:http://linkedlifedata.com/resource/pubmed/id/16549526

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4 Pt 1
pubmed:dateCreated
2006-3-21
pubmed:abstractText
Classical phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase, resulting in an accumulation of its upstream metabolite phenylalanine in brain tissue and cerebrospinal fluid of PKU patients. PKU is neuropathologically characterized by reduced dendritic arborization, loss of synapses, and neurodegeneration. We investigated whether increased concentrations of phenylalanine cause reduced synaptic density and alter dendritic branching. We treated primary cortical neurons differentiated for 21 d in vitro with 5 mM phenylalanine in the presence of all essential amino acids. Immunocytochemical analysis of 12 and 21 d in vitro primary neurons revealed no changes of dendritic morphology or neuronal viability but a significant difference in synaptic density, suggesting that elevated concentrations of extracellular phenylalanine cause an impairment of synaptogenesis. Although impairment of cerebral energy metabolism has been identified as an important pathophysiological principal in many diseases, respiratory chain function has not been extensively studied in PKU before. We investigated whether phenylalanine inhibits respiratory chain complexes I-V. In vitro analysis revealed no inhibitory effect of phenylalanine on complexes I-V, but an inhibition of pyruvate kinase, a key enzyme of glycolysis, catalyzing the formation of pyruvate. Pyruvate kinase is part of the enzyme assay to investigate enzyme activity of mitochondrial complex V and it remains to be elucidated whether this finding is relevant in vivo. In conclusion, elevated concentrations of phenylalanine might be involved in mechanisms underlying impaired synaptogenesis in PKU, supporting the common therapeutic strategy to reduce phenylalanine concentrations in the brain to prevent neurodegeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0031-3998
pubmed:author
pubmed:issnType
Print
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
544-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Phenylalanine reduces synaptic density in mixed cortical cultures from mice.
pubmed:affiliation
Department of General Pediatrics, University of Children's Hospital, Heidelberg, Germany. friederike_hoerster@med.uni-heidelberg.de
pubmed:publicationType
Journal Article