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Effect of experimental hyperphenylalaninemia on the postnatal rat brain
Author(s) -
Ushakova Alina A.,
Gubkina Helena A.,
Kachur Victoria A.,
Lepekhin Eugene A.
Publication year - 1997
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(96)00081-0
Subject(s) - hyperphenylalaninemia , cerebrum , cerebellum , medicine , endocrinology , biology , phenylalanine , extracellular , central nervous system , neuroscience , biochemistry , amino acid
The molecular mechanism of the disturbance to brain development caused by phenylketonuria remains mostly unknown. We have studied three molecular markers that reflect the development of neurons, glia and the extracellular matrix of the postnatal rat brain in an animal model of hyperphenylalaninemia, in order to elucidate the possible mechanism by which increased phenylalanine influences brain development. The contents of NCAM, GFAP and hyaluronate‐binding activity were compared in cerebellum and telencephalon of normal rats and those subjected to high phenylalanine. No statistically significant changeswere found in telencephalon when experimental animals were compared to controls. In the hyperphenylalaninemic cerebellum, the developmental dynamic of NCAM content (represented by two peaks at about postnatal days 5 and 22 during normal development) is dramatically altered. The GFAP content in the cerebellum of treated rats exceeded those in controls significantly during late developmental stages (postnatal days 28–35). Hyaluronate‐binding activity in the extracellular protein fraction from treated rat cerebellum was increased compared to normal rat at the early stages of development only (postnatal day 7). These results suggest that high serum phenylalanine may lead to permanent brain dysfunction through a disturbance of a wide range of developmental events.