A Chemical Investigation of the Defects of Myelination in Phenylketonuria

Crome, L.; Tymms, V.; Woolf, L. I.

doi:10.1136/jnnp.25.2.143

Cited by 113 publications

(32 citation statements)

References 27 publications

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“…Recently the white matter of some of these brains has been examined chemically. A marked loss of total solids and a lower content of cerebrosides and cholesterol than in the white matter of the normal brain were the chief findings (Crome et al 1962). This is strong evidence of failure to myelinate or of loss of myelin, and is in accordance with the histological evidence of a reduction in the number of myelinated fibres per unit of volume; however, chemical examination revealed deficient myelination even in cases where no abnormality was detected histologically.…”

Section: Galactosemiasupporting

confidence: 66%

Inborn errors of metabolism

Sawley

1998

Paediatric Nursing

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Section: Galactosemiasupporting

confidence: 66%

Inborn errors of metabolism

Sawley

1998

Paediatric Nursing

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“…The differences in staining between the ClPhe + Phe-treated and the control animals may be a reflection of a defect similar to that found upon comparing the biochemistry of normal myelin and myelin from subjects with PKU. Such studies show a markedly lower cerebroside content of the white matter in phenylketonurics (22).…”

Section: Discussionmentioning

confidence: 99%

“…After delivery, 12 litters were assigned to the control group given saline and 22 (11). After the rats were decapitated, the brain was exposed and the head immersed in formalin-saline for 48 hr.…”

Section: Model Phenylketonuria Productionmentioning

confidence: 99%

The Enduring Behavioral Changes in Rats with Experimental Phenylketonuria

Andersen

Rowe

Guroff

1974

Proc. Natl. Acad. Sci. U.S.A.

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The biochemical features of phenyl- ClPhe + Phe in adult rats to produce a lowered hepatic phenylalanine hydroxylase activity and an elevated blood phenylalanine level without associated tyrosinemia. When rats were treated with this regimen before they were weaned, during the critical first 21 days of life, they showed, during the treatment period, biochemical (3) and electrophysiological (4) abnormalities typical of PKU. Their behavioral abnormalities persisted throughout adult life (5). The present work is directed toward extending the previous investigations of model PKU in rats, especially in the area of permanent learning deficits which result from the early treatment with ClPhe + Phe. Other recent investigations using ClPhe + Phe as a method of PKU production include the behavioral studies of Vorhees et al. (6) and Butcher et al. (7,8) and the biochemical studies of Edwards and Blau (9, 10). METHODS Model phenylketonuria productionThis procedure is identical to that reported previously (5 Activity Measurements. Each subject was introduced into an activity wheel (Lafayette Instrument Company) at 5 p.m. and removed at 8 a.m. the next morning (15 hr). Male subjects were tested first: 16 that had been given saline and 16 that had been given ClPhe + Phe. At the time of their initial activity measurement they ranged in age from 26 to 32 weeks. To test the reproducibility of this activity test, a second test was administered to the males 2 weeks after the first. Females (22 that had been given saline and 31 that had been given ClPhe + Phe) ranged between 32 and 38 weeks of age at the time of activity testing. Their activity measurement was not repeated. No subjects having cataracts were included in any behavioral testing except as noted below.Active Avoidance in a Two-Way Shuttlebox. Males (10 given saline and 10 given ClPhe + Phe) were tested at about 6 months of age; females (7 given saline and 6 given ClPhe + Phe) were tested at about 10 months of age.Active Avoidance Learning with a Right-Left Choice in a Modified Shuttlebox. The two-way shuttlebox was modified for right-left choice experiments in the following way: one side, side A, was left unchanged. The other side, side B, was divided in two to form a right-and left-hand compartment. Testing took place over 4 days. On day 1, the subject was allowed to explore the apparatus for 15 min. On day 2, the subject's right-left preference was determined. On day 3, the animal was trained to choose the side opposite its natural preference. Criterion performance was defined as the number of trials required to make nine consecutive correct choices. Each trial was accomplished as follows: The subject was introduced

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“…The discrepancy between the results obtained by Petre-Quadens and Jouvet [54] and by Feinberg et al [20] and our results may be because these authors mainly investigated adult subjects. Long lasting mental retardation with convulsions and myelination deficits [1,13,22,45,56] rather than a disturbance in the noradrenaline/serotonin balance may account for the decreased amount of REM sleep found by these authors in many different mental retardates including subjects with PKU. Petre-Quadens and Jouvet [54] did all night recordings and Feinberg et al [20] even studied several consecutive nights, whereas our results are based on the analysis of a few total sleep cycles.…”

Section: Relevance Of Results In Relation To Biochemical Theories Of mentioning

confidence: 99%

Sleep Patterns in Hyperphenylalaninemia: A Lesson on Serotonin to be Learned from Phenylketonuria

et al. 1973

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ExtractSleep behavior and bioelectric brain development have been studied by means of polygraphic recordings (respiration, eye movements, muscle activity, and electroencephalogram (EEG)) in 22 infants and young children with phenylketonuria (PKU). The EEGs were analyzed by a special visual pattern recognition program as well as by means of computer spectral analysis. The distribution between rapid eye movement (REM) or active and non-REM (NREM) or quiet sleep was not found to be different from control infants of the same age. Quite contrary to current theories on the biochemical regulation of sleep as derived from acute animal experiments, our results indicate that, under chronic conditions, a normal sequence of quiet and active sleep can be maintained despite a severe lack of blood and cerebrospinal fluid serotonin as it occurs in hyperphenylalaninemia. In the EEG of subjects with PKU the development of a rhythm or sleep spindle (12-16 cps) activity was enhanced and already abnormal as early as 5 weeks after term birth. The frequency of a waves as well as of hypnagogic, monomorphic, 6 activity was shifted toward higher values. Dietary treatment of 4-6 weeks duration and normalization of blood phenylalanine levels did not significantly change the abnormal bioelectric phenomena. SpeculationThe increase in high frequency regular rhythmic activity in the sleep EEG of subjects with PKU can be explained by decreased concentrations of inhibitory synaptic transmitters such as serotonin and 7-aminobutyric acid. The developmental course in the expressivity of sleep spindles during the 1 st year of life, together with reliable methods of quantified EEG analysis, seems to be a rather sensitive indicator of normal or abnormal brain maturation. Introductionshould be, in theory, alterations of sleep behavior be-

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A Chemical Investigation of the Defects of Myelination in Phenylketonuria

Cited by 113 publications

References 27 publications

Inborn errors of metabolism

Inborn errors of metabolism

The Enduring Behavioral Changes in Rats with Experimental Phenylketonuria

Sleep Patterns in Hyperphenylalaninemia: A Lesson on Serotonin to be Learned from Phenylketonuria

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