First Month Of Postnatal Life Research Articles

Dendritic development in neocortex of infants with early postnatal life undernutrition

The structure of large pyramidal cells from layer V of the motor cortex of undernourished and well-nourished infants was studied to determine the effects of postnatal nutrition on cortical dendritic development. In undernourished infants, the arborization and span of the basilar dendrites were decreased in comparison to controls. These findings indicated that undernutrition experienced during the first months of postnatal life could affect the growth of pyramidal cells, especially the formation of basilar dendrites.

Development and cytodifferentiation of peritubular myoid cells in the rat testis.

The cytodifferentiation of peritubular myoid cells was studied in developing rats from fetal day 18 through approachment of puberty. The parameters taken into consideration were 1) the presence of desmin, a component of intermediate filaments in contractile cells; 2) the expression of alkaline phosphatase, a cell surface enzyme present in no other cell type of the seminiferous tubule; 3) the expression of the smooth muscle specific isoform of alpha-actin, a marker of terminal differentiation in smooth muscle cells; 4) cell proliferation rate, evaluated in radioautography as labeling index after incorporation of 3H-thymidine in short-term organ culture; and 5) cytoarchitectural changes detected with scanning electron microscopy. By means of immunofluorescence and cytochemistry it was observed that the three markers are expressed early during life, long before the onset of the first spermatogenic wave; in particular desmin is already present in fetal samples and alkaline phosphatase activity appears a few days after birth, whereas alpha-smooth muscle isoactin is first detected around birth. As for myoid cell replication, the high prenatal labeling index was found to drop soon after birth and to further slow down during the first month of postnatal life, suggesting that myoid cell proliferation is not a major factor in peritubular expansion. SEM examination of developing peritubulum has shown that, when approaching puberty, the myoid cell undergoes a dramatic change in cytoarchitecture, consisting in extreme flattening and cytoplasmic expansion resulting in an apparent increase in peritubular surface.

The Role of Lipids in Nutrition during the First Months of Life

The most important functional components of dietary lipids (triglycerides, cholesterol esters and phospholipids) are fundamental to normal growth and development of infants. Fatty acids are classified according to their chain length and their degree of saturation. Each class of fatty acid is involved in specific metabolic reactions: short-chain fatty acids act as local growth factors in the colon; medium- and saturated long-chain fatty acids are a good source of energy; polysaturated long-chain fatty acids are involved in metabolic regulation; and very long-chain fatty acids are important structural components of membranes. The development of the central nervous system depends on the amount and the quality of the lipid supply in the last months of prenatal and the first months of postnatal life. Placental cord blood during foetal life and breast milk provide fatty acids in the correct amounts and ratios. Fats in breast milk provide half the infant's calorific needs and maternal dietary habits can influence the lipid composition of milk. The preparation of blends of fats for formulas is under investigation in order to improve the lipid quality and to make formulas more similar to breast milk. A major goal of current research is to define the nutritional and metabolic relationships between fatty acid groups and between fats and the other dietary sources of calories in order to improve the composition of infant formulas, in particular for premature babies.

Deterioration of hearing function in mice with neural crest defect

Cochlear potentials were recorded in black-eyed white-mutant mice (strains W/W v and Sl/Sl d) during the first months of postnatal life. In these animals melanocytes from the neural crest do not reach the stria vascularis. Hearing thresholds indicated by the compound action potential of the auditory nerve progressively increased. Hearing loss in comparison with the control CBA mice amounted 40 dB six weeks after birth, at eight months practically all mutants were deaf. Endocochlear potential was near zero already in the majority of 6 week-old animals. Abnormalities were observed also in intracellular potentials of the stria vascularis cells which were recorded in vitro and dye-marked. While in marginal cells of CBA mice positive potentials of about 10 mV were recorded, potentials of marginal cells in mutants were near zero. Basal cell potentials were negative in CBA mice (approximately − 25 mV) and positive in young mutants (approximately + 12 mV). However, in mutants older than 3 months the intracellular potentials of basal cells changed to negativity (approximately −10 mV). The results demonstrate gradual deterioration of hearing function observed in both W/W v and Sl/Sl d mutants during first months of the postnatal life. In addition to the dysfunction of stria vascularis, where intermediate cells are missing, also the function of receptors progressively deteriorates.

Development of temperature regulation in the common white-toothed shrew, Crocidura russula

1. 1. Body temperature and oxygen consumption were measured during the first month of postnatal life in two litters of Crocidura russula at four different ambient temperatures. 2. 2. Body temperature in the nest varies from 30.5–35.0°C during the first 10 days; afterwards it becomes more constant (35.5–37.0°C). 3. 3. First homoiothermic reactions occur on the 2nd day of life and become effective on the 4th day. 4. 4. In the case of undernourished shrews, torpor is already developed on the 2nd day. 5. 5. After the 7th day torpor is the obligatory reaction in cooling experiments. 6. 6. This discontinuous development of temperature regulation is interpreted as typical for shrews capable of torpor.

Sensitivity of auditory cortical neurons of kittens to monaural and binaural high frequency sound

The experiments reported here describe the abilities of young auditory cortical neurons to encode information about tone bursts having frequencies above 2.5 kHz. The studies were carried out in anesthetized kittens ranging from 8 to 44 days of age. At all ages studied, stimulation of the contralateral ear was most effective in evoking spikes. Typically the response was confined to stimulus onset. Thresholds were comparatively high and response latencies were comparatively long in the youngest kittens studied. The time course of threshold development was very similar to that of the auditory nerve and cochlear nuclei indicating that most, if not all, age related thresholds and threshold changes at the cortical level are accounted for by mechanisms operating at the level of the cochlea and auditory nerve. Response latency shortened progressively over the first month of postnatal life and while the absolute change in response latency differed considerably from that of cells in the cochlear nuclei the proportional changes were very similar. These data indicate that the comparatively long response latency and latency changes recorded at the cortex are imposed by underdeveloped central auditory processes. Response areas of kitten cortical neurons resembled those of the adult. At all ages studied, binaural interactions were robust and similar in kind to those recorded in adult cats. We conclude that cortical neurons of kittens preserve the results of interactions occurring at lower brainstem levels and that the development of the circuits of which these neurons are a part develop as a functional unit.

Expression of cell type-specific markers during pancreatic development in the mouse: implications for pancreatic cell lineages

The islet cells of the mammalian pancreas are comprised of four different endocrine cell types, each containing a specific hormone. Islet cells also contain two enzymes of the catecholamine biosynthetic pathway : tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). The cell lineage relationships of these different cell types have not been examined and it is not known whether, during development, they originate from the same or from different precursor populations. In this study we used immunocytochemical procedures to determine whether developing pancreatic cells express markers common to endocrine and exocrine cell types. We found that acinar cell precursors express AADC prior to the appearance of an exocrine marker and that the expression of AADC in acinar cells persists throughout embryogenesis to the first month of postnatal life. At this time, acinar cells do not contain AADC. We also found that exocrine cells containing AADC never express other islet-cell markers. These findings suggest that while acinar and islet cells both arise from precursor cells containing AADC, these progenitor cells do not express a combined endocrine-exocrine phenotype.

ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-GONADAL (HPG) AXIS IN PRETERM FEMALES

Precocious puberty was observed in a preterm ( 27 wks post-conceptional age - PCA) female. At 41 wks PCA, estradiol (E2) levels were elevated (282 pg/ml). By 13 months PCA, E2 decreased spontaneously (18 pg/ml) and pubertal changes regressed. However, pelvic ultrasonography revealed the development of ovarian cysts. In order to interpret these findings and determine their significance, we studied 6 normal preterm female infants (PCA ≤34 wks) during the first month of postnatal life. We measured: a) E2 - max > 30,000 pg/ml on day of birth (DOB), b) LH - max 196 mIu/ml on DOB, c) FSH - max 125.2 mIu/ml 3 wks after birth, d) 17-hydroxyprogesterone - max 4320 ng/dl on DOB, and e) DHEA-S - max 429 μg/dl on DOB. As in full term infants, E2 was highest on the DOB and decreased to prepubertal values within 1 month. In contrast, gonadotropin levels were variable but remained elevated throughout this period.Conclusions: Although in most preterm females elevated gonadotropin levels persist for at least 1 month, the same is not true for E2. These data suggest that the HPG axis is activated in premature female infants prior to their would be term delivery. The index case differed in that elevated E2 levels persisted and ovarian cysts developed.

Effects of prenatal ethanol exposure on physical growth, sensory reflex maturation and brain development in the rat.

In the offspring of ethanol-treated rats during gestation (25% ethanol in drinking water) decreased litter size, increased postnatal mortality rate, reduced body weight and body size, delayed ear opening, eyelid opening and teeth eruption, retarded air righting reflex acquisition, impaired brain growth, reduced cortical thickness and delayed maturation of layer Vth's pyramidal neurons: reduced basilar dendritic arborization and decreased number of spines in the apical dendrite, were observed when compared with age-matched controls fed with a standard diet. Minimal effects were found in the offspring of fibre-treated rats during gestation (standard diet mixed with cellulose) in which the body weight was similar to that of controls, although both the calorific intake from food and the mother's weight gain during pregnancy were similar to those of the ethanol-treated group. All these abnormal parameters became normal at the end of the first month of postnatal life, indicating recovery of these developmental defects produced by prenatal ethanol consumption.

Formation of "caudate spindles" in the rabbit sensomotor cortex during ontogeny

Electrical activity of the sensomotor and visual areas of the neocortex during stimulation of the caudate nucleus was recorded in young rabbits aged 3–60 days and in adults. Single stimulation of the caudate nucleus was found to cause the appearance of characteristic bursts of spindle-like rhythmic activity ("caudate spindles"), described previously in cats and monkeys, in the adult rabbit cortex. The latent period of the caudate spindle was about 200 msec, its duration 1–3 sec, and the frequency of its oscillations of the order of 12 Hz. Caudate spindles were most marked in the sensomotor cortex of the ipsilateral hemisphere. In rabbits under 10 days old caudate spindles were not found even if the intensity of stimulation was increased many times. Starting from the age of 15 days bursts of rhythmic activity resembling caudate spindles, but with lower frequency (about 8 Hz), longer latent period (up to 350 msec), and also with a higher threshold, appeared in the sensomotor cortex. The definitive type of caudate spindles was established toward the end of the first month of postnatal life, corresponding to the time of formation and complication of conditioned-reflex activity in developing animals.

P-Aminohippurate (PAH) transport and Na-k-ATPase activity in rat renal cortical slices during postnatal maturation and drug-induced stimulation

PAH transport and Na-K-ATPase activity markedly increase during the first month of postnatal life. Pretreatment of rats with PAH or cyclopenthiazide induces a stimulation of in vitro PAH accumulation in renal cortical slices, whereas Na-K-ATPase activity is unchanged in comparison to saline-pretreated controls. 5 mM ouabain in the incubation medium reduces PAH accumulation. Developmental pattern and stimulation effects are pronounced as in controls. The ouabain-insensitive component of net PAH accumulation progressively increases with age and is significantly enhanced following drug pretreatment, whereas the ouabain-sensitive component of net PAH accumulation shows relatively slight modifications. Consequently, Na-K-ATPase seems not to be linked with postnatal maturation or drug-induced stimulation in tubular PAH transport.

Reduced activity during development delays the normal rearrangement of synapses in the rabbit ciliary ganglion.

The number of preganglionic axons that innervate individual ciliary ganglion cells has been investigated after cutting one or both optic nerves in new-born rabbits. In agreement with previous work (Johnson & Purves, 1981), ciliary ganglion cells in normal rabbits lose, on average, about one-half of their inputs from preganglionic axons during the first month of post-natal life. Although severing one optic nerve at birth abolished the subsequent appearance of the direct pupillary light response on that side, ciliary ganglion cells of normal neonatal rabbits are driven synaptically in the absence of direct retinal illumination when tested in vivo. This tonic activity persisted for at least 3 months after interruption of the optic nerve at birth. Thus neonatal optic nerve section reduced, but did not eliminate, synaptic activation of ciliary ganglion cells. Optic nerve section at birth delayed the elimination of synaptic connexions in the ipsilateral but not the contralateral ciliary ganglion. Through the first 4 post-natal weeks ciliary ganglion cells on the operated side had, on average, more than the normal number of inputs from preganglionic axons. By 8 weeks of age, however, the normal number of connexions was established in spite of the unilateral visual deprivation. The elimination of connexions in ganglia on the unoperated side followed a normal time course. The effect of bilateral optic nerve section on synaptic rearrangement was the same as the ipsilateral effect after cutting only one optic nerve. It is concluded that the rate of synaptic rearrangement in this ganglion is slowed by a chronic reduction of synaptic activity.

Source of cholesterol for the ocular lens, studied with U18666A: A cataract-producing inhibitor of lipid metabolism

Cholesterol is the major lipid component of the ocular lens. The source of lens cholesterol during the first month of post-natal life of the rat was investigated by use of U18666A, a potent inhibitor of cholesterol biosynthesis which can also produce cataracts. Lenses from rats treated with U18666A at a level known to produce cataracts were of smaller size and accumulated total sterol at about one-half the rate of untreated controls. The lens content of phospholipid also lagged behind that of controls. Desmosterol accounted for 50–75% of the total sterol in lens of all treated rats, this paralleled the percent content of desmosterol in liver and serum of these animals. Lenses taken from 20-day-old treated rats and incubated in vitro synthesized little digitonide-precipitable sterol (DPS) from 3H 2O as compared to lenses from age-matched controls. The steady state concentration of U18666A in lens was found to be 1–2 × 10 −6 m; this concentration almost completely blocked sterol synthesis in vitro when added to normal lenses. Although U18666A inhibited lens synthesis in vitro of phospholipids from 1,3-[ 3H]-glycerol and 32P i, it did so only at levels much higher than those encountered in vivo. Thus, the changes seen in lens phospholipids appear secondary to the decreases in sterols. Since lenses of treated rats synthesized little if any sterol but accumulated sterol at one-half the rate of control lens, we conclude that during early post-natal development of the rat the ocular lens possesses the potential to satisfy about one-half of its sterol requirements from sources outside of the lens, perhaps from lipoproteins in aqueous humor. This conclusion is consistent with our earlier work which indicated that the rat's lens can furnish 50–100% of its total cholesterol by synthesis de novo during the first two weeks of life and less thereafter. The relationship of the inhibition of sterol synthesis to production of the U18666A-induced cataract is discussed.

Pathological effects of in utero methylmercury exposure on the cerebellum of the golden hamster : I. Early effects upon the neonatal cerebellar cortex

Pregnant golden hamsters ( Mesocricetus auratus) were given either a single dose of 10 mg methylmercury/kg on gestational day 10 or daily doses of 2 mg/kg on gestational days 10–15. Cerebella of experimental and control offspring were examined by light and electron microscopy during the first month of postnatal life. Degenerative changes, characterized by accumulations of lysosomes and areas of floccular cytoplasmic degradation, were frequently observed in neuroblasts of the external granular layer (EGL) as well as in more differentiated neural elements in the molecular and internal granular layers. Pyknotic nuclei were seen singly and in groups throughout the EGL of treated animals. Developing dendrites appeared particularly sensitive to methylmercury. Affected dendrites were swollen and packed with degenerating cytoplasmic material. Astrocytes and perivascular macrophages also contained large aggregates of irregular electron-opaque debris, lysosomes, and large lipid droplets. Pathological alterations in the cerebellum were most pronounced during the first 15 days of postpartum life.

Embryonic and foetal myosins in human skeletal muscle: The presence of foetal myosins in duchenne muscular dystrophy and infantile spinal muscular atrophy

Recently described techniques for separating myosin isoenzymes have been adapted for analysis of myosins from diseased and developing human skeletal muscle. The method is highly suitable for analysis of human myosins because only 2–3 mg of muscle are required for routine analyses. Human embryonic/foetal myosins are electrophoretically distinct from mature skeletal myosins, and are not normally detected beyond the first month of post-natal life, except in premature infants. They have a high alkaline calcium-activated ATPase activity. This would account for the histochemical classification of foetal fibres as “Type II”, although physiological differences between adult fast-twitch muscle and foetal muscle are well recognized. Foetal myosins are also synthesized in human skeletal muscle under certain pathological circumstances. Their presence in Duchenne dystrophy probably reflects the associated marked muscle regeneration, with immaturity of some muscle cells. The large amounts of foetal myosin present in many cases of infantile spinal muscular atrophy is evidence that innervation is necessary for the normal cessation of foetal myosin synthesis.

Effects of bromocriptine in developing rat pups after 6-hydroxydopamine

The effects of low (0.5 mg/kg) and high (2.0 mg/kg) doses of bromocriptine (BCR) on activity and escape performance were examined during the first month of postnatal life in normal developing rat pups and littermates treated at 5 days of age with a combination of desmethylimipramine and 6-hydroxydopamine (6-OHDA). Such a procedure resulted in significant reductions in brain dopamine to concentrations 10–20% of vehicle controls while norepinephrine was unaffected. BCR increased general motor activity in vehicle pups at 13 and 19 days but had little effect on more mature animals. Pups who had not received BCR exhibited a decline in activity over the hour long observation period (habituation of activity) but this decline was abolished by both low (0.5 mg/kg) and high (2.0 mg/kg) doses of the agent. Stereotyped activity, particularly at 19 days was increased by BCR in 6-OHDA pups but not in vehicle animals, an effect suggesting denervation supersensitivity. Head dips in a hole box at 30 days of age were not influenced by BCR in vehicle pups but significantly reduced by BCR in 6-OHDA pups, suggesting that BCR might be acting to stimulate inhibitory dopaminergic mechanisms. Escape learning in a T-maze at 20 days and shuttle box at 28 days was disrupted by high doses of BCR in vehicle pups and both doses of BCR in 6-OHDA animals. The similarity with the behaviors observed in the clinical syndrome of attention deficit disorder with hyperactivity prompted a number of investigative groups including our own to suggest that the 6-OHDA model might serve as a useful and convenient paradigm to evaluate pharmacological agents that offer potential in the treatment of this most common disorder. From this perspective we would predict that BCR would have little clinical utility since it both failed to attenuate 6-OHDA induced hyperactivity and tended to disrupt performance in an avoidance learning task.

Development of Brush Border Peptidases in Human and Rat Small Intestine during Fetal and Neonatal Life

The cytosol peptidase activities hydrolyzing glycl-L-leucine and L-leucyl-glycine as well as the activities of the brush border peptidases (oligoaminopeptidase, aminopeptidase A, gamma-glutamyl-transpeptidase, dipeptidyl-aminopeptidase IV, and carboxypeptidase) are present in rat fetuses during the early differentiation of the intestine (17th to 19th days of fetal life); they increase then at a different rate, reaching a maximum at various times, in the second and third wk after birth, and then decrease to the adult values during the first month of postnatal life. Only the oligoaminopeptidase activity increases steadily after birth, reaching maximal activity in the last decade of the first month. In human fetuses aged between 8 and 22 wk, the gamma-glutamyltranspeptidase was the only brush border peptidase found to be higher than in adults and children. On the other hand, the aminopeptidase A is remarkably reduced. The dipeptidylaminopeptidase IV and the carboxypeptidase are already at adult level in the youngest fetuses, and the oligoaminopeptidase increases during the period of fetal life studied; at the end of this period, the enzyme activity does not differ from the values found in children and adults. The small intestine of the term and preterm newborn should, therefore be able, with some possible exceptions, to efficiently digest peptides.

Cerebellar tRNA methyltransferases: A development study

Developmental patterns of homologous and heterologous tRNA methylation by cerebellar tRNA methyltransferases are described. The study revealed that: (a) homologous tRNA methylation results in the predominant formation of N 2-methyl-guanine and 1-methyladenine; (b) tRNA methyltransferases of bulk-isolated Purkinje and granule cells methylate E. coli tRNA glu 2 in vitro in a characteristic manner, and (c) the methylation of 8-day-old cerebellar, cortical and hepatic tRNA in vivo yields tRNAs containing different proportions of methylated bases. The findings suggest that the presumably cell-specific populations of cerebellar tRNA methyltransferases continue to alter their substrate recognition characteristics up to and beyond the first month of post-natal life.

α-Melanocyte-Stimulating Hormone and Adrenocorticotropin in the Regulation of Glucocorticoid Secretion during the Perinatal Period in Sheep*

To determine the role of other ACTH-like peptides in the regulation of glucocorticoid secretion in fetal sheep, we examined the responses of the adrenal gland of fetal and newborn sheep to comparable single doses of alpha MSH (75 micrograms) or ACTH (50 micrograms) during the last third of gestation and the first month of postnatal life. alpha MSH first increased the plasma glucocorticoid concentration at 121--130 days of gestation [from 16 +/- 1.5 to 36.9 +/- 9 (SE) ng/ml]; the response to alpha MSH persisted on days 131--140 of gestation and during the first month after birth. ACTH first increased the plasma glucocorticoid concentration at 131--140 days of gestation and increased it further in the first month after birth (from 18.9 +/- 3.6 to 97.0 +/- 10 ng/ml). The observations that the adrenal glands of fetuses and newborn lambs responded to alpha MSH at a dose comparable to that of ACTH and that the response to alpha MSH in the fetus preceded the response to ACTH may indicate that adrenal receptors mature during fetal development. These data also suggest that the regulation of the adrenal during fetal life may involve more than one tropic hormone.

The growth and development of fat cells in infancy.

Studies on the development of adipose tissue in infancy would seem essential to test the hypothesis that adult fat stores relate to the numbers of fat cells developed during early childhood. Thirty infants aged from 1-28 months and 13 fetuses of approximately 11-16 weeks of gestation obtained at therapeutic abortion and two preterm infants of 28 weeks of gestation were studied. The cells of both fetal and infant adipose tissue were separated from connective tissue and fixed by treatment with osmium tetroxide in buffered collidine using a method modified from Hirsch and Gallian (J. Lipid Res.,9:100(1968) for estimation of cell size and number. In fetal and early infancy there are two populations of cells in adipose tissue. Small cells found in tissue before birth and the first months of postnatal life do not contain fat. The larger cells, which are fat containing, represent maturing fat cells. They are cells which include fat cells recognized by previous workers but up to 24.6% were found to be less than 25 micron in diameter. Small cells in the early stages of fat accumulation may make an important contribution to the cell population of fat mass. It is apparent that increasing fat accumulation in the first 6-12 months of life, as demonstrated by increased skinfold thickness measurements, is associated with increasing fat cell size and that this association bears a linear relationship.