Phenylalanine Reduces Synaptic Density in Mixed Cortical Cultures from Mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-04

AUTHORS

FRIEDERIKE HÖRSTER, MARINA A. SCHWAB, SVEN W. SAUER, JOACHIM PIETZ, GEORG F. HOFFMANN, JÜRGEN G. OKUN, STEFAN KÖLKER, STEFAN KINS

ABSTRACT

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. More... »

PAGES

544-548

Identifiers

URI

http://scigraph.springernature.com/pub.10.1203/01.pdr.0000203091.45988.8d

DOI

http://dx.doi.org/10.1203/01.pdr.0000203091.45988.8d

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043159291

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16549526


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1203/01.pdr.0000203091.45988.8d'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1203/01.pdr.0000203091.45988.8d'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1203/01.pdr.0000203091.45988.8d'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1203/01.pdr.0000203091.45988.8d'


 

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