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Loss of neurotransmitter receptors by hyperphenylalaninemia in the HPH‐5 mouse brain
Author(s) -
Hommes FA
Publication year - 1994
Publication title -
acta pædiatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/j.1651-2227.1994.tb13469.x
Subject(s) - hyperphenylalaninemia , hippocampus , endocrinology , medicine , neurotransmitter , neurotransmitter receptor , receptor , muscarinic acetylcholine receptor , cerebral cortex , acetylcholine , cortex (anatomy) , muscarinic acetylcholine receptor m4 , neuroscience , phenylalanine , biology , biochemistry , amino acid
The binding of the muscarinic acetylcholine antagonist quimiclinidylbensilate to its specific receptors was measured by quantitative autoradiography in the brain of the HPH‐5 mouse, a phenylalanine hydroxylase‐deficient mouse mutant, as a model for human PKU. Three types of response to a hyperphenylalaninemic condition were observed: no effect as in the putamen; a gradual decrease over time such as in several areas of the cerebral cortex and the hippocampus; a transient increase, followed by a decrease, such as in the frontal area of the cerebral cortex. Of particular significance is the effect on the CA 1 and CA 3 layer of the hippocampus, since this structure has been implicated in the acquisition and storage of long‐term memory. Hyperphenylalaninemia leads to a decrease in neuro‐transmitter receptor density and, therefore, to a decrease in connectivity, which may form the basis for the mental retardation in this condition.