Utilization of acetate by chick brain during postnatal maturation.

1. The study of the compartmentation of glutamate metabolism has been performed in the chick brain in vivo and in vitro in the presence of [U-14C]acetate between day 1 and day 30 of postnatal maturation. 2. The compartmentation of glutamate metabolism in vivo appears between day 1 and day 4 after hatching in the cerebral hemispheres and optic lobes. It is however more precocious in the optic lobes. In the cerebellum, it appears later, at about day 4 after hatching. The compartmentation of glutamate metabolism appears at the same time as the rapid incorporation of glucose into amino acids takes place in the cerebral hemispheres and the optic lobes. 3. In the chick telencephalon in vitro, the compartmentation of glutamate metabolism is visible from day 1 after hatching onwards. This difference is undoubtedly linked to the absence of an interference of glucose metabolism with acetate metabolism in vitro, and to the presence of a third compartment in the cerebral slices.     

Utilization of ketone bodies by chick brain and spinal cord during embryonic and postnatal development

Lipid synthesis from acetoacetate and 3-hydroxybutyrate was studied in chick embryo from 15 to 21 days and in chick neonate from 1 to 21 days. Embryonic spinal cord showed higher ability than brain to incorporate acetoacetate into total lipids, although a sharp decrease was found at hatching. 3-Hydroxybutyrate incorporation into total lipids was also higher in spinal cord than in brain, especially during the embryonic period. Phospholipids were the main lipids formed in both tissues from both precursors. An appreciable percentage of radioactivity was also recovered as free cholesterol, especially during the embryonic phase. The developmental patterns of amino acid synthesis from acetoacetate and 3-hydroxybutyrate were similar in both tissues: a clear increase after hatching was followed by a decrease at day 4 of neonatal life. Acetoacetate was a better substrate for amino acid synthesis than 3-hydroxybutyrate during the embryonic development in both tissues. Oxidation of both precursors to CO₂ strongly decreased between 15 and 21 days of embryonic development both in brain and spinal cord.     

RNA synthesis in neuronal and glial cell nuclei from rat cerebral hemispheres during early postnatal development

RNA synthesis in rat cerebral hemispheres at 1, 5, and 10 days of age and the relative contribution brought by neuronal and glial nuclei to RNA synthesis was investigated. The experiments were carried out both in vivo (by i.p. injection of [³H]uridine) and in vitro (either by incubation of tissue slices with [³H]uridine or by determination of RNA polymerase activities). The labeling of RNA decreases from 1 to 10 days of age both in vivo and in vitro; the decrease is of the same extent in neuronal and glial nuclei. RNA polymerase activity Mg²⁺-dependent does not change significantly from 1 to 10 days of age either in total, in neuronal, or in glial nuclei, whereas the Mn²⁺-dependent activity increases significantly over the same developmental period studied. The significance of RNA polymerase assay as an index of in vivo RNA synthesis is discussed.     

Uptake and metabolism of [3H]norepinephrine in the cerebral hemispheres of chick embryos

Abstract— The uptake and metabolism of [³H]norepinephrine were studied in slices of cerebral hemispheres removed from chick embryos at 10, 15 and 20 days of embryonic age, as well as from 90-day-old hens. Brain tissue from all age groups concentrated [³H]norepinephrine to much greater levels at 37°C than at 0°C. There was a marked increase in the rate of accumulation of [³H]norepinephrine in tissues from 10 to 15 days of embryonic age, with no further increase in the rate observed from 15 to 20 days of embryonic age. Tissue slices were incubated for 20 min with [³H]norepinephrine, and the deaminated metabolites of norepinephrine were separated by paper chromatography. In tissues from all age groups, the neutral metabolites were produced in greater amounts than the acid metabolites. A significant increase in the amounts of deaminated metabolites formed was observed in the period from 10 to 15 days of embryonic age and a significant decrease in the amounts formed was observed in the period from 15 to 20 days of embryonic age. The deamination at 20 days was very similar to that observed in the adult. A significant decrease in the level of the deaminated metabolites was noted in all age groups in response to cocaine (an inhibitor of neuronal uptake mechanisms), an observation suggesting that mechanisms for neuronal uptake of NE are functional by 10 days of embryonic development in the chick. However, a significant increase in the level of deaminated metabolites in response to reserpine (an inhibitor of uptake of NE into storage granules) was observed only in slices taken from 20-day embryos and from the 90-day-old hen. The effect in the hen was more prominent than in the 20-day embryo. These results were interpreted to indicate that mechanisms for the uptake of NE develop at an earlier embryonic age than mechanisms for the storage of NE and that mechanisms for storage continue to develop after hatching.     

Utilization in vivo of glucose carbon in the optic lobes and the cerebellum of the chick during postnatal growth.

1. The incorporation of glucose carbon in vivo into amino acids was studied in the chick optic lobes and cerebellum during postnatal growth after subcutaneous injection of [U-14C]glucose. 2. The rapid incorporation of glucose carbon into free amino acids appears between the 1st and the 2nd day of postnatal growth in the optic lobes and between the 1st and the 4th day after hatching in the cerebellum. 3. The period during which the properties of mature brain metabolism are obtained is characterized in both structures during the first 48 hr of postnatal growth by changes in the specific radioactivity of some amino acids such as aspartate and alpha-alanine, and also by transient increases of glucose and glutamine concentrations. 4. The gamma-aminobutyrate content in the optic lobes is very high; the cerebellum on the contrary is characterized by its low gamma-aminobutyrate concentration linked to a very fast metabolism of this amino acid.     

Soluble guanylyl cyclase during postnatal porcine pulmonary maturation

The nitric oxide (NO)/cGMP pathway plays a key role in the regulation of pulmonary vascular tone during the transition from the fetal to the neonatal circulation, and it is impaired in pathophysiological conditions such as pulmonary hypertension. In the present study, we have analyzed the changes in the function and expression of soluble guanylyl cyclase (sGC) in pulmonary arteries during early postnatal maturation in isolated third-branch pulmonary arteries from newborn (3-18 h of age) and 2-wk-old piglets. The expression of sGC beta(1)-subunit in pulmonary arteries increased with postnatal age both at the level of mRNA and protein. The catalytic region of porcine sGC beta(1) was sequenced, showing a 92% homology with the human sequence. This age-dependent increase in sGC expression correlated with increased vasorelaxant responses to the physiological sGC activator NO and to the exogenous sGC activator YC-1, but not to the membrane-permeable cGMP analog 8-bromoguanosine 3',5'-cyclic monophosphate. In conclusion, an increased expression of sGC in pulmonary conduit arteries from 2-wk-old compared with newborn piglets explains, at least partly, the age-dependent increase in the vasorelaxant response of NO and other activators of sGC.     

Aminophylline modulation of the mouse respiratory network changes during postnatal maturation.

Aminophylline is a respiratory stimulant commonly used for the treatment of central apnea. Experiences from clinical practice, however, revealed that aminophylline is not reliably effective in preterm infants, whereas it is normally effective in infants and mature patients. In an established animal model for postnatal development of respiratory control mechanisms, we therefore examined the hypothesis that the clinical observations reflect a developmental change in the sensitivity of the central respiratory network to methylxanthines. The medullary respiratory network was isolated at different postnatal ages (postnatal days 1-13; P1-P13) in a transverse mouse brain stem slice preparation. This preparation contains the pre-B?tzinger complex (PBC), a region that is critical for generation of respiratory rhythm. Spontaneous rhythmic respiratory activity was recorded from the hypoglossal (XII) rootlets and from neurons in the PBC by using the whole cell patch clamp technique. Bath-applied aminophylline [20 microM] increased the frequency (+41%) in neonatal animals (P1-P6) without affecting the amplitude of respiratory burst activity in XII rootlets. The same concentration of aminophylline did not have any significant effect on the frequency of respiratory XII bursts but increased the amplitude (+31%) in juvenile animals (P7-P13). In the same age group, aminophylline also augmented the amplitude and the duration of respiratory synaptic drive currents in respiratory PBC neurons. The data demonstrate that augmentation of the respiratory output is due to direct enhancement of central respiratory network activity and increase of synaptic drive of hypoglossal motoneurons in juvenile, but not neonatal, animals. This indicates a developmental change in the efficacy of aminophylline to reinforce central respiratory network activity. Therefore, we believe that the variable success in treating respiratory disturbances in premature infants reflects maturational changes in the expression of receptors and/or intracellular signal pathways in the central respiratory network.     

Glutaminase activity in the chick central nervous system during postnatal growth.

1. Glutaminase activity was evaluated in the chick cerebral hemispheres, optic lobes and cerebellum between the 1st and 30th day of postnatal growth. 2. Glutaminase activity is higher in the cerebral hemispheres than in the optic lobes and is lowest in the cerebellum. 3. It seems to be inversely related to the magnitude of the variations of glutamine concentration in the three areas. 4. No direct relation exists between enzyme activity and glutamate concentration in the three tissues.     

Some data on postnatal maturation of the cerebral cortex in cat

This paper describes the neurons in different cortical areas and traces their postnatal changes. Rapid Golgi and Golgi--Kopsch impregnation were carried out in 1-day-old and 9-day-old kittens. The maturation of the pyramidal neurons can be observed mainly on their basal dendritic orientation and on development of the dendritic spines. The differentiation of the interneurons (non-pyramidal) also proceeds on the first postnatal days. These, though slightly less mature than the associated pyramidal neurons, are identifiable already on the first postnatal day. It is concluded that there are significant differences in the maturation of the neurons in the various cortical areas.     

Effect of hypothyroidism on the biogenesis of free mitochondria in the cerebral hemispheres and in cerebellum of rat during postnatal development

The effect of propylthiouracil-induced neonatal hypothyroidism on some aspects of the biogenesis of free (non-synaptosomal) mitochondria in the cerebral hemispheres and in the cerebellum of developing rat has been studied. The results obtained show that in hypothyroid rats mitochondrial DNA synthesis is delayed, mitochondrial RNA synthesis is not affected and cytochrome aa₃ content of mitochondria is lower than in controls. Furthermore ultrathin sections of 14-and 21-day old hypothyroid rat cerebella show mitochondria with an altered ultrastructural organization and large intracristal spaces.     

Acetylcholine chloride and renal hemodynamics during postnatal maturation in conscious lambs.

To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with postnatal age, we measured parameters of renal hemodynamics before and for 35 s after aortic suprarenal injection of acetylcholine in conscious, chronically instrumented lambs aged approximately 1 wk (n = 5) and approximately 6 wk (n = 5). Acetylcholine was administered in one of five doses ranging from 0 to 10 mg/kg body wt; doses were administered randomly, in the same volume. There were significant age- and dose-dependent changes in renal vascular resistance after acetylcholine administration, such that the response was greater in 1-wk-old lambs. After the highest dose tested, renal vascular resistance decreased by 13.6 +/- 7.3 (SD) mmHg. ml(-1). min. g kidney wt in 1-wk-old lambs and by 9.1 +/- 3.2 mmHg. ml(-1). min. g kidney wt in 6-wk-old lambs at 35 s. We also observed a transient renal vasoconstriction before the renal vasodilatation in 6-wk-old lambs but not in 1-wk-old animals. These data provide the first age- and dose-dependent effects of exogenous administration of acetylcholine on renal hemodynamics during maturation in conscious animals.     

Protein metabolism in the cerebral hemispheres during the emotional-algesic stress

Emotional-algesic stress causes essential changes in the protein metabolism of cerebral hemispheres. These changes may be of great importance for the functioning of the brain and cause the disturbances of the higher nervous activity when the organism is influenced by the emotional stress factors.