scholarly journals Effect of phenylalanine on protein synthesis in the developing rat brain

1970 ◽  
Vol 117 (2) ◽  
pp. 325-331 ◽  
Author(s):  
H. C. Agrawal ◽  
A. H. Bone ◽  
A. N. Davison

1. Inhibition of the rate of incorporation of [35S]methionine into protein by phenylalanine was more effective in 18-day-old than in 8-day-old or adult rat brain. 2. Among the subcellular fractions incorporation of [35S]methionine into myelin proteins was most inhibited in 18-day-old rat brain. 3. Transport of [35S]methionine and [14C]leucine into the brain acid-soluble pool was significantly decreased in 18-day-old rats by phenylalanine (2mg/g body wt.). The decrease of the two amino acids in the acid-soluble pool equalled the inhibition of their rate of incorporation into the protein. 4. Under identical conditions, entry of [14C]glycine into the brain acid-soluble pool and incorporation into protein and uptake of [14C]acetate into lipid was not affected by phenylalanine. 5. It is proposed that decreased myelin synthesis seen in hyperphenylalaninaemia or phenylketonuria may be due to alteration of the free amino acid pool in the brain during the vulnerable period of brain development. Amyelination may be one of many causes of mental retardation seen in phenylketonuria.

1969 ◽  
Vol 115 (5) ◽  
pp. 1051-1062 ◽  
Author(s):  
N. L. Banik ◽  
A. N. Davison

1. Subcellular fractions and myelin were isolated from developing and adult rat brain. 2. Measurements of chemical composition and enzyme activities indicate the presence of a second myelin-like fraction mainly in the brain of developing rats. 3. This membrane fraction has a different lipid composition from myelin, but resembles myelin in its content of phosphohydrolase and aminopeptidase activity. 4. It is suggested that the second myelin-like fraction may be a submicrosomal contaminant or it may be derived from oligodendroglial plasma membrane during myelinogenesis.


1992 ◽  
Vol 68 (3) ◽  
pp. 756-766 ◽  
Author(s):  
T. M. Perney ◽  
J. Marshall ◽  
K. A. Martin ◽  
S. Hockfield ◽  
L. K. Kaczmarek

1. The gene for a mammalian Shaw K+ channel has recently been cloned and has been shown, by alternative splicing, to give rise to two different transcripts, Kv3.1 alpha and Kv3.1 beta. To determine whether these channels are associated with specific types of neurons and to determine whether or not the alternately spliced K+ channel variants are differentially expressed, we used ribonuclease (RNase) protection assays and in situ hybridization histochemistry to localize the specific subsets of neurons containing Kv3.1 alpha and Kv3.1 beta mRNAs in the adult and developing rat brain. 2. In situ hybridization histochemistry revealed a heterogeneous expression pattern of Kv3.1 alpha mRNA in the adult rat brain. Highest Kv3.1 alpha mRNA levels were expressed in the cerebellum. High levels of hybridization were also detected in the globus pallidus, subthalamus, and substantia nigra reticulata. Many thalamic nuclei, but in particular the reticular thalamic nucleus, hybridized well to Kv3.1 alpha-specific probes. A subpopulation of cells in the cortex and hippocampus, which by their distribution and number may represent interneurons, were also found to contain high levels of Kv3.1 alpha mRNA. In the brain stem, many nuclei, including the inferior colliculus and the cochlear and vestibular nuclei, also express Kv3.1 alpha mRNA. Low or undetectable levels of Kv3.1 alpha mRNA were found in the caudate-putamen, olfactory tubercle, amygdala, and hypothalamus. 3. Kv3.1 beta mRNA was also detected in the adult rat brain by both RNase protection assays and by in situ hybridization experiments. Although the beta splice variant is expressed at lower levels than the alpha species, the overall expression pattern for both mRNAs is similar, indicating that both splice variants co-expressed in the same neurons. 4. The expression of Kv3.1 alpha and Kv3.1 beta transcripts was examined throughout development. Kv3.1 alpha mRNA is detected as early as embryonic day 17 and then increases gradually until approximately postnatal day 10, when there is a large increase in the amount of Kv3.1 alpha mRNA. Interestingly, the expression of Kv3.1 beta mRNA only increases gradually during the developmental time frame examined. Densitometric measurements indicated that Kv3.1 alpha is the predominant splice variant found in neurons of the adult brain, whereas Kv3.1 beta appears to be the predominant species in embryonic and perinatal neurons. 5. Most of the neurons that express the Kv3.1 transcripts have been characterized electrophysiologically to have narrow action potentials and display high-frequency firing rates with little or no spike adaptation.(ABSTRACT TRUNCATED AT 400 WORDS)


1976 ◽  
Vol 154 (2) ◽  
pp. 559-560 ◽  
Author(s):  
M M. Sudjic ◽  
R Booth

Rat brain contains 3-hydroxy-3-methylglutaryl-CoA reductase activity, but this enzyme is far more active in 7-day-old brain than in adult brain. This difference may partly explain why cholesterol biosynthesis is more rapid in growing than in adult rat brain.


1976 ◽  
Vol 154 (2) ◽  
pp. 265-269 ◽  
Author(s):  
H C Agrawal ◽  
K Fujimoto ◽  
R M Burton

The turnover of classical Folch-Lees proteolipid proteins was studied after administration of [2,3-3H]tryptophan to both developing and adult rat brain. The animals were killed from 2h to 250 days after subcutaneous injections of [3H]tryptophan. The measured specific radioactivity in developing brain attained maximum value 24h after the administration of label, whereas the total radioactivity per brain reached a maximum 21 days after injection. The half-life of proteolipid protein from the measured specific radioactivity was 7-20 days, depending on the time-points used for the calculation, whereas calculation from total radioactivity between 28-77 and 91-257 days gave half-lives of 35-40 and 188 days respectively. In contrast, in animals injected at 40 days of age, the half-life from the whole-brain-radioactivity data was 188 days. The problem of the recycling of radioactivity for the synthesis of myelin proteins from either a general or a discrete amino acid pool is discussed.


1976 ◽  
Vol 154 (2) ◽  
pp. 517-527 ◽  
Author(s):  
W Berthold ◽  
L Lim

High-molecular-weight RNA was isolated from rat brain at various times after the intracranial administration of [32P]Pi. The synthesis of 28S and 18S rRNA could be detected within 1h of the injection of the radioactive precursor and appeared to be more pronounced, relative to other high-molecular-weight RNA, in the brains of older rats compared with those of newborn rats. Polyadenylated RNA, representing most mRNA and their precursors, was isolated by chromatography on oligo(dT)-cellulose. The contribution of this polyadenylated RNA to total RNA synthesis was investigated in the cerebral cortex and the phylogenetically older brain stem at different stages in the development of the rats by using a 5h period of labelling as an arbitrary index of transcription. In the brain stem the proportion of labelled polyadenylated RNA comprised 27-30% of the total RNA. The corresponding values for the cortex decreased from 34% in newborn rats to 23% in 40-150-day-old rats. These data indicated that proportionately more polyadenylated RNA is synthesized in the cortex of the newborn than in the adult rat and that there is a progressive decrease in the synthesis of polyadenylated RNA relative to rRNA during development.


1971 ◽  
Vol 122 (5) ◽  
pp. 759-763 ◽  
Author(s):  
H. C. Agrawal ◽  
A. N. Davison ◽  
L. K. Kaczmarek

The concentration of taurine and the activities of cysteinesulphinate decarboxylase and glutamate decarboxylase have been measured in rat brain. During development, taurine exhibited a decrease in concentration unrelated to the activity of cysteinesulphinate decarboxylase which increased during the same period. The distribution of taurine in subcellular fractions of adult and 7-day-old rat brain was typical of most amino acids, whereas half of the cysteinesulphinate decarboxylase activity was found in the nerve-ending cytoplasm. In anatomical distribution, taurine displayed great regional heterogeneity but both cysteinesulphinate decarboxylase and glutamate decarboxylase were more evenly distributed. Hypertaurinaemia was shown to have no effect on the entry of glycine into the brain or on its utilization in protein synthesis.


1988 ◽  
Vol 8 (4) ◽  
pp. 598-605 ◽  
Author(s):  
M. Kirikae ◽  
M. Diksic ◽  
Y. L. Yamamoto

An autoradiographic method for the measurement of the rate of valine incorporation into brain proteins is described. The transfer coefficients for valine into and out of the brain and the rate of valine incorporation into normal rat brain proteins are given. The valine incorporation and the transfer constants of valine between different biological compartments are provided for 14 gray matter and 2 white matter structures of an adult rat brain. The rate of valine incorporation varies between 0.52 ± 0.19 nmol/g/min in white matter and 1.94 ± 0.47 in inferior colliculus (gray matter). Generally, the rate of valine incorporation is about three to four times higher in the gray matter than in the white matter structures.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Karin Warfvinge ◽  
Diana Krause ◽  
Lars Edvinsson

Abstract Background Recent work, both clinical and experimental, suggests that the hypothalamic hormone oxytocin (OT) and its receptor (OTR) may be involved in migraine pathophysiology. In order to better understand possible central actions of OT in migraine/headache pathogenesis, we mapped the distribution of OT and OTR in nerve cells and fibers in rat brain with a focus on areas related to migraine attacks and/or shown previously to contain calcitonin gene related peptide (CGRP), another neuropeptide involved in migraine. Methods Distribution of OT and OTR in the adult, rat brain was qualitatively examined with immunohistochemistry using a series of well characterized specific antibodies. Results As expected, OT was extensively localized in the cell somas of two hypothalamic nuclei, the supraoptic (SO or SON) and paraventricular nuclei (Pa or PVN). OT also was found in many other regions of the brain where it was localized mainly in nerve fibers. In contrast, OTR staining in the brain was mainly observed in cell somas with very little expression in fibers. The most distinct OTR expression was found in the hippocampus, the pons and the substantia nigra. In some regions of the brain (e.g. the amygdala and the hypothalamus), both OT and OTR were expressed (match). Mismatch between the peptide and its receptor was primarily observed in the cerebral and cerebellar cortex (OT expression) and hippocampus (OTR expression). Conclusions We compared OT/OTR distribution in the CNS with that of CGRP and identified regions related to migraine. In particular, regions suggested as “migraine generators”, showed correspondence among the three mappings. These findings suggest central OT pathways may contribute to the role of the hypothalamus in migraine attacks.


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