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Long‐lasting Effect of Maternal Hyperphenylalaninemia during Pregnancy on Postnatal Brain Development of Mice: Biochemical and Morphological Studies
Author(s) -
YAMAWAKI Yasushi,
OHYA Noriaki,
SHIMADA Morimi
Publication year - 1995
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.1995.tb00611.x
Subject(s) - hyperphenylalaninemia , offspring , pregnancy , endocrinology , medicine , phenylalanine , biology , hippocampal formation , cerebrum , placenta , fetus , central nervous system , amino acid , biochemistry , genetics
The effect of maternal hyperphenylalaninemia on postnatal brain development was examined. Maternal hyperphenylalaninemia was induced by giving chow supplemented with 6% phenylalanine (Phe.) and 0.12% p‐chlorophenylalanine (PCPA) for at least one month before coupling and then throughout pregnancy. Offspring from hyperphenylalaninemic mothers were given a normal diet from the first day after birth. Infant mice were killed on the 21st, 28th and 56th day after birth. The protein, RNA and DNA in the brain were measured to determine the biochemical changes. Maturation of the dendrite of pyramidal cells was also examined by the Golgi method. The body weight of the offspring born to mothers, which had been treated with Phe. and PCPA during pregnancy, was significantly less than that of the control. The gain of cerebral weight showed a similar pattern with that to the body weight. The total protein, RNA and DNA contents in the cerebrum of the treated group were also reduced significantly on 21st, 28th and 56th days after birth. The dendritic arborization of the cortical pyramidal neurons in the layer V showed significant reductions in the offspring born to hyperphenylalaninemic mothers compared with the age‐matched control at 21, 28 and 56 days after birth. These findings suggest that maternal hyperphenylalaninemia during pregnancy causes an irreversible retardation of the neuronal maturation both biochemically and morphologically, and subsequently gives rise to disorders of the higher cortical functions.