High level of orexin A observed in the phenylketonuria mouse brain is due to the abnormal expression of prepro-orexin.
Orexins/hypocretins are recently discovered neuropeptides, synthesized mainly in the lateral hypothalamus of the brain. Orexins regulate various functions including sleep and apetite. We recently reported increased amount of orexin A in the phenylketonuria (PKU) mouse brain. Whether this is caused by overexpression of the precursor for orexins, prepro-orexin was studied in the PKU mouse brain. Microarray expression analysis revealed overexpression of orexin gene in the brain of PKU mouse. Quantitative real-time RT-PCR showed increased level of prepro-orexin mRNA in the PKU mouse brain. In addition, expression of genes associated with cell signal and growth regulation was also affected in the PKU mouse brain, as observed by microarray analysis. These data suggest that up-regulation of orexin mRNA expression is the possible factor for inducing high orexin A in the brain of PKU mouse. The metabolic environment in the brain of PKU mouse affects normal expression of other genes possibly to result in pathophysiology seen in the PKU mouse, if documented also in patients with PKU.
Surendran
Sankar
S
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
Rady
Peter L
PL
Szucs
Sylvia
S
Michals-Matalon
Kimberlee
K
Tyring
Stephen K
SK
Matalon
Reuben
R
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D000068797:Orexins; D010649:Phenylalanine / Q000378:metabolism; D010661:Phenylketonurias / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D018698:Glutamic Acid; D010649:Phenylalanine; D005680:gamma-Aminobutyric Acid