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Biomedical subjects

G N Fuller

Publications and source records attributed to G N Fuller.

At least 127 records · Page 7Linked to original sources

The relationship between nutritional adequacy and brain myelin accumulation: a comparison of varying degrees of well fed and undernourished rats.

Rats undernourished through 17 days of age to produce mild weight lag (less than 20%) had either the same amount, or slightly more myelin than well fed controls. Schedules of undernourishment producing approximately 30, 40 and 50% body weight lags produced corresponding rank-ordered myelin deficits of 25, 55 and 60%, respectively. Brain growth was relatively spared in all cases, never exceeding a deficit of 10%. Absolute myelin deficits did not recover following nutritional rehabilitation, although myelin continued to increase in both normal and all test populations.

Animals↗

Brain hypomyelination during postnatal undernourishment: a comparison of proteolipid protein synthesis versus assembly into membrane.

A double isotope methodology which permits the separate analysis of (i) the synthesis of myelin proteolipid protein and (ii) its subsequent assembly into myelin membrane was applied to the case of postnatal undernourishment of rats. Results showed that brain proteolipid protein synthesis was greatly depressed, indicating that undernourishment limited the production of myelin components. This is a different result from that obtained in the mouse Quaking mutant, in which case component formation is normal whereas their assembly into myelin membrane is blocked. The results have possible implications regarding cellular development of oligodendroglia of undernourished rats.

Animals↗

Postnatal increase in the metabolism of leucine and valine.

The catabolism of tritium-labeled leucine, valine, and glycine was determined by measuring the appearance of tritium-labeled water at various postnatal and adult ages in rats. Results for leucine and valine show a marked increase in the formation of labeled water during the 3rd postnatal week. The partial exclusion of leucine and valine from brain, as a result of the blood-brain barrier, particularly enhances observation of labeled water formation in that the product (water) and precursor (amino acid) are largely separated (supporting experiments demonstrate the prior existence of the blood-brain barrier for leucine). Results for glycine indicate its extensive metabolic degradation at all postnatal ages. These data indicate that the metabolic rate of intraperitoneally administered, radioactively labeled leucine and valine changes appreciably during early postnatal development. The early postnatal manifestation of human disorders of branched-chain amino acid metabolism is consistent with the chronology of development in the rat.

Age Factors↗

Catecholamines in rat brain following postnatal undernutrition and nutritional rehabilitation.

Norepinephrine and dopamine were examined in 19 discrete brain areas from the telencephalon, diencephalon, and mesencephalon of nutritionally rehabilitated adult rats following postnatal undernutrition from birth through 21 days of age. Following rehabilitation, catecholamine levels were not significantly different from control values in any of the areas examined. Catecholamine concentrations in young, undernourished rats are generally elevated (either from stress or from nutritional insufficiency). Data presented here show that whichever case is true, the early effect of undernourishment is transient and that normal values are restored by nutritional rehabilitation.

Amygdala↗

A possible effect of the methylxanthines caffeine, theophylline and aminophylline on postnatal myelination of the rat brain.

A double isotope methodology was used to assess the effect of methylxanthine administration on membrane protein synthesis in developing rat brain. Rat pups were given either aminophylline, theophylline, or caffeine in a dosage of 40 mg/kg or 80 mg/kg daily from the second postnatal day through 20 days of age. Results show depressed myelin protein synthesis at 21.24 days by theophylline (80 mg/kg) and caffeine (40 and 80 mg/kg). Synthesis was essentially normal at 27-28 days of age, indicating a possible delay in development followed by a 'catch-up' phenomenon.

Aging↗

The relative numbers of oligodendroglia in different brain regions of normal and postnatally undernourished rats.

The relative numbers of oligodendroglia were compared in representative brain regions of 21 day old undernourished and control rats. As a result of postnatal undernutrition which produced half normal body weights and a 10-15 percent reduction in brain weight, the relative numbers of oligodendroglia were slightly increased in photomicrographs of corticospinal tract (a motor tract), medial lemniscus (a sensory tract), red nucleus (a motor nucleus) and somatosensory cortex. Relative numbers were reduced in the corpus callosum, and the thickness of the corpus callosum was significantly reduced. Cell sizes of oligodendroglia were essentially normal throughout the brain, although some reductions of 5 to 6 percent were observed. Areas of brain structures in cross section were essentially unchanged. We have previously hypothesized that nutritionally induced brain hypomyelination results from a reduction in the specific numbers of oligodendroglia and consequently a lasting reduction in the brain myelin concentration. The present results are inconsistent with this hypothesis, as both the density of oligodendroglia and sizes of brain regions are essentially normal. We know from prior work using the same model of nutritional deprivation that myelin synthesis is greatly reduced. Consequently an important depressant effect of undernourishment on oligodendroglia in the developing brain involves either the communication between axons and oligodendroglia leading to myelin induction or the synthetic capacity to make myelin.

Animals↗

A morphometric comparison of central and peripheral hypomyelination induced by postnatal undernourishment of rats.

Developing Long-Evans rats were undernourished to produce a body-weight deficit of 39% at the age of weaning. Well-nourished litter mates were used as controls. Morphometric analyses were made of pyramidal tracts and posterior tibial nerves of each animal. In measuring pyramidal tract, we observed that axonal circumferences of myelinated fibers were smaller in the undernourished rats and that the number of myelin lamellae per axon appeared reduced by a small amount. The most striking observation in the undernourished rats compared to the controls was that the proportion of myelinated fibers was decreased by 40% at 20 days of age. Axon circumferences of nonmyelinated axons were not measured. Similar decreases were observed in myelinated axon circumference and myelin lamellae of posterior tibial nerves of undernourished rats. Because of sampling problems, we did not attempt to compare the proportion of myelinated and nonmyelinated fibers in posterior tibial nerves of undernourished and well-nourished rats. These morphometric data, particularly the reduction of myelinated fibers, are consistent with biochemical studies of brain hypomyelination in undernourished rats. The data indicate that the mechanism of hypomyelination in nutritionally deprived rats involves a failure of the "trigger" by which myelin-forming cells begin to sheath axons in myelin.

Animals↗

Chronic halothane modification of eeg-like activity recorded from somatosensory cortex and deep nuclei in freely behaving rats.

Chronic exposure to the anesthetic agent halothane has been implicated in morphological and biochemical alterations of central nervous system tissue. In the present experiments, analysis of electroencephalographic (EEG) recordings has been used to examine effects on brain electrical activity. EEGs were recorded from freely behaving rats with stereotaxically implanted permanent semimicroelectrodes. Recordings were taken from the somatosensory cortex (SC), nucleus parafasciculus thalami (PF), mesencephalic central gray (CG), and the ventromedial hypothalamus (VMH) before (control) and after 28 and 56 days of chronic intermittent halothane administration (0.5%, 3 hr/day, 5 days/week). On each recording day (0, 28 and 56), EEGs were obtained prior to halothane exposure and following exposure to 0.25%, 0.5% and 1.5% halothane. In halothane-naive rats (day 0), the EEG dominant frequency (DF) showed a dose-response pattern consisting of an initial increase with 0.25% (significant only for the PF) followed by suppression at 0.5% and a marked significant decrease in all regions at 1.5%. On day 28, the pre-drug DF recorded from three of four regions showed a slowing trend. Additionally, with 1.5% halothane, only the SC DF was significantly decreased. Following 56 days of intermittent exposure, the pre-drug EEG frequencies were significantly decreased in all regions as compared to naive values. Subsequent administration of 0.25% halothane produced a significant increase in all regional DFs which was also obtained with 0.5% and with 1.5% for the CG and VMH. The high DF values from the PF, CG and VMH at 0.5% and from the CG and VMH at 1.5% represent statistically significant increases over naive 1.5% values. Chronic halothane exposure is thus shown to progressively alter EEG activity and the EEG pattern of dose-responsiveness in four brain regions.

Anesthetics, Inhalation↗

The effect of postnatal undernourishment on epileptiform kindling of dorsal hippocampus.

Rats were undernourished postnatally from birth through 20 days of age. They were subsequently tested for susceptibility to motor seizures kindled in hippocampus in adulthood. Compared to littermate control animals the postnatally undernourished rats were more susceptible to the kindling treatment. We conclude that early postnatal undernourishment has a permanent effect on susceptibility of the hippocampus to electrically-induced seizures.

Animals↗

Relative synthesis of myelin in different brain regions of postnatally undernourished rats.

We used a double isotope procedure and starved and normal littermate rats to compare relative protein synthesis in the cerebellar nuclear, myelin, synaptosomal, mitochondrial, and microsomal subfractions of postnatally starved animals. The remaining brain tissue was dissected into 6 additional regions (cerebral cortex, medulla oblongata, midbrain, hippocampus, striatum, and hypothalamus) and these were frozen for similar subcellular fractionation and analysis at a later date. The microsomal fraction derived from frozen tissues was discarded. The results show that early postnatal starvation specifically depresses myelin synthesis to about the same extent in all major brain regions at 18 and 21 days of age.

Animals↗