High levels of orexin A in the brain of the mouse model for phenylketonuria: possible role of orexin A in hyperactivity seen in children with PKU
Campbell, G. A.
Tyring, S. K.
McDonald, J. David
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Surendran, S.; Campbell, G. A.; Tyring, S. K.; Matalon, K.; McDonald, J. David; Matalon, R. 2003. High levels of orexin A in the brain of the mouse model for phenylketonuria: possible role of orexin A in hyperactivity seen in children with PKU. Neurochem Research, v.28 no.12 pp.1891-1894
Phenylketonuria (PKU) is a metabolic disorder caused by phenylalanine hydroxylase deficiency leading to increased levels of phenylalanine in the brain. Hyperactivity is reportedly induced by a high level of orexin A, and therefore orexin A content was studied in the PKU mice. Hypothalamus and brain stem had higher levels of orexin A compared to cerebrum and cerebellum both in wild type and PKU mice brains as observed by radioimmunoassay method. Interestingly, all these regions of the brain in PKU mouse showed a higher level of orexin A compared to the wild type. Heart and plasma also had higher levels of orexin A in PKU compared to the wild type. Immunohistochemical analysis revealed an increased number of orexin A-stained cells in the brain and heart of PKU mouse compared to the wild type. This is the first report of increased level of orexin in the PKU mouse brain. Hyperactivity is commonly observed in children with PKU; thus these findings suggest that orexin A is a contributing factor for the hyperactivity.
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