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Sample records for early postnatal development

  1. Oligodendrocytes as Regulators of Neuronal Networks during Early Postnatal Development

    PubMed Central

    Ramos, Maria; Ikrar, Taruna; Kinoshita, Chisato; De Mei, Claudia; Tirotta, Emanuele; Xu, Xiangmin; Borrelli, Emiliana

    2011-01-01

    Oligodendrocytes are the glial cells responsible for myelin formation. Myelination occurs during the first postnatal weeks and, in rodents, is completed during the third week after birth. Myelin ensures the fast conduction of the nerve impulse; in the adult, myelin proteins have an inhibitory role on axon growth and regeneration after injury. During brain development, oligodendrocytes precursors originating in multiple locations along the antero-posterior axis actively proliferate and migrate to colonize the whole brain. Whether the initial interactions between oligodendrocytes and neurons might play a functional role before the onset of myelination is still not completely elucidated. In this article, we addressed this question by transgenically targeted ablation of proliferating oligodendrocytes during cerebellum development. Interestingly, we show that depletion of oligodendrocytes at postnatal day 1 (P1) profoundly affects the establishment of cerebellar circuitries. We observed an impressive deregulation in the expression of molecules involved in axon growth, guidance and synaptic plasticity. These effects were accompanied by an outstanding increase of neurofilament staining observed 4 hours after the beginning of the ablation protocol, likely dependent from sprouting of cerebellar fibers. Oligodendrocyte ablation modifies localization and function of ionotropic glutamate receptors in Purkinje neurons. These results show a novel oligodendrocyte function expressed during early postnatal brain development, where these cells participate in the formation of cerebellar circuitries, and influence its development. PMID:21589880

  2. Amphetamine treatment during early postnatal development transiently restricts somatic growth

    PubMed Central

    Smith, Andrew M.; Chen, Wei-Jung A.

    2010-01-01

    Aims Restricted somatic growth during fetal or early postnatal periods has been suggested to serve as a predictive indicator for neuroanatomical changes and behavioral impairments during adulthood. Here, the effects of d-amphetamine sulphate (AMPH) exposure during the brain growth spurt period on this potential indicator were evaluated. Main Methods Rats received 0, 5, 15 or 25 mg/kg/day of AMPH via two daily intragastric intubations from PD4-9. Body weight data were collected every other day from PD1 to 21, and then weekly until PD59. On PD9, a subset of animals was terminated 90 min after the last amphetamine treatment and the weights of the cortex, cerebellum, and brainstem were collected. Weights of these brain regions from young adult rats were also assessed on PD68. Key Findings AMPH exposure during early postnatal development limited somatic growth in a dose-related manner, with significantly lower body weights in animals assigned to the AMPH 25 and AMPH 15 groups. However, this was transient in nature, with no significant difference in weight observed after pups were weaned on PD21. Further, no differences in brain weight were observed at either age as a result of AMPH exposure. Significance These findings support the idea that developmental AMPH exposure transiently restricts somatic growth. Moreover, the lack of effect on brain weight shows that AMPH differentially affects somatic and brain growth. The current findings suggest that in addition to the immediate effects on body weight, amphetamine may alter the rate of growth, and increase the risk for weight-related adult diseases. PMID:20153755

  3. Impact of Early Postnatal Androgen Exposure on Voice Development

    PubMed Central

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  4. Impact of early postnatal androgen exposure on voice development.

    PubMed

    Grisa, Leila; Leonel, Maria L; Gonçalves, Maria I R; Pletsch, Francisco; Sade, Elis R; Custódio, Gislaine; Zagonel, Ivete P S; Longui, Carlos A; Figueiredo, Bonald C

    2012-01-01

    The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.

  5. Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

    PubMed

    Munoz-Valverde, D; Rodríguez-Rodríguez, P; Gutierrez-Arzapalo, P Y; López de Pablo, A L; Carmen González, M; López-Giménez, R; Somoza, B; Arribas, S M

    2015-01-01

    Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming.

  6. Periodization of the early postnatal development in the rat with particular attention to the weaning period.

    PubMed

    Ošt'ádalová, I; Babický, A

    2012-01-01

    The early postnatal period is characterized by a great plasticity with critical windows in which any inadequate insult or intervention may be able to influence both positively and adversely postnatal growth and development. After birth the rat littermates enter the presuckling period (initial 6 hours terminated by the first nursing), characterized by transition from the amniotic fluid to the air, by the changes of the ambient temperature, by the termination of placental nutrition and by oxidative stress. After this stage the suckling period initiates and the littermates start to consume milk of their mothers. Comsumption of milk culminates on day 15, then decreases and terminates on postnatal day 28. The end of the suckling period and the onset of physiological weaning is determined by the moment when the youngs for the first time consume the solid food together with milk (postnatal day 17 in rats). On day 19 the first intake of drinking water occurs. The weaning period terminates by the last consumption of maternal milk - on postnatal day 28. It is necessary to stress that the duration of early postnatal periods is independent of the changes of body weight. The precise knowledge of individual ontogenetic periods critical for further development is crucial for the prediction and explanation of reactions to various pathogenetic stimuli both under experimental conditions and in clinical medicine.

  7. [Effects of early postnatal exposure to dieldrin on synaptic development of striatum in mice].

    PubMed

    Gao, Ye; Wang, Qu-nan; Wu, Shan

    2012-02-01

    To investigate the effects of early postnatal exposure to dieldrin on striatum synaptic development in lactation, adolescence and adulthood of mice. The pups were divided into 5 groups randomly. Three groups were exposed to dieldrin (0.01% DMSO solution) at doses of 0.2, 2.0 and 20.0 microg/kg and two control groups were exposed to DMSO or saline by intraperitoneal injection of every other day from postnatal days (PND) 3 to PND13. The striatum were isolated from brain in lactation (PND14), adolescence (PND36) and adulthood (PND98). Western blot assay was used to detect the expression levels of striatal synaptic proteins. The postnatal exposure to dieldrin could reduce the level of growth associated protein (GAP43) of striatum in lactation in a dose-dependent manner. In adolescence, the level of glial fibrillary acidic protein (GFAP) in striatum increased and the levels of tyrosine hydroxylase (TH), GAP43 and post-synaptic density protein 95 (PSD95) decreased with exposure doses. The level of Synapsin I decreased in adolescence male mice. The changes of expression levels of GFAP, TH and PSD95 proteins lasted to adulthood. Early postnatal exposure to dieldrin could affect the expression level of GAP43 protein in striatum. The expression levels of TH and PSD95 proteins in striatum decreased in adolescence and adulthood. These results indicated that the early postnatal exposure to dieldrin may persistently interfere in the striatal synaptic development.

  8. Early postnatal development of GABAergic presynaptic inhibition of Ia proprioceptive afferent connections in mouse spinal cord.

    PubMed

    Sonner, Patrick M; Ladle, David R

    2013-04-01

    Sensory feedback is critical for normal locomotion and adaptation to external perturbations during movement. Feedback provided by group Ia afferents influences motor output both directly through monosynaptic connections and indirectly through spinal interneuronal circuits. For example, the circuit responsible for reciprocal inhibition, which acts to prevent co-contraction of antagonist flexor and extensor muscles, is driven by Ia afferent feedback. Additionally, circuits mediating presynaptic inhibition can limit Ia afferent synaptic transmission onto central neuronal targets in a task-specific manner. These circuits can also be activated by stimulation of proprioceptive afferents. Rodent locomotion rapidly matures during postnatal development; therefore, we assayed the functional status of reciprocal and presynaptic inhibitory circuits of mice at birth and compared responses with observations made after 1 wk of postnatal development. Using extracellular physiological techniques from isolated and hemisected spinal cord preparations, we demonstrate that Ia afferent-evoked reciprocal inhibition is as effective at blocking antagonist motor neuron activation at birth as at 1 wk postnatally. In contrast, at birth conditioning stimulation of muscle nerve afferents failed to evoke presynaptic inhibition sufficient to block functional transmission at synapses between Ia afferents and motor neurons, even though dorsal root potentials could be evoked by stimulating the neighboring dorsal root. Presynaptic inhibition at this synapse was readily observed, however, at the end of the first postnatal week. These results indicate Ia afferent feedback from the periphery to central spinal circuits is only weakly gated at birth, which may provide enhanced sensitivity to peripheral feedback during early postnatal experiences.

  9. Sexually dimorphic effects of postnatal allopregnanolone on the development of anxiety behavior after early deprivation.

    PubMed

    Zimmerberg, Betty; Kajunski, Elizabeth W

    2004-07-01

    Stress early in life exerts persistent detrimental effects on brain development. In this experiment, a rodent model of child neglect, early deprivation (ED), was used to investigate the role of the neurosteroid allopregnanolone [AlloP; 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP)] in the development of anxiety behavior. Subjects were either undisturbed controls or ED: separated individually for 6 h per day from postnatal day (PN) 2 to 6. Control and ED subjects were also either noninjected, vehicle-injected or injected with 5 mg/kg AlloP prior to the isolation. At PN 7, responses to 2.5 or 5 microg icv injections of AlloP were determined for separation-induced ultrasonic vocalizations (USVs). Tolerance to the USV-reducing effect of daily AlloP was seen in control but not ED pups, and daily AlloP reversed the expected ED suppression of USVs. As adults, controls treated with postnatal AlloP were less anxious than all other groups on the elevated plus maze. ED counteracted this effect. Male controls showed a reversal of the typical sex difference. There were no effects on open-field activity. These results suggest that the neonatal brain is responsive to alterations in AlloP levels, and that neuroactive progesterone metabolites may play a role in mediating the development of stress-related sex differences.

  10. Longitudinal analyses of prenatal and postnatal lead exposure and early cognitive development

    SciTech Connect

    Bellinger, D.; Leviton, A.; Waternaux, C.; Needleman, H.; Rabinowitz, M.

    1987-04-23

    In a prospective cohort study of 249 children from birth to two years of age, we assessed the relation between prenatal and postnatal lead exposure and early cognitive development. On the basis of lead levels in umbilical-cord blood, children were assigned to one of three prenatal-exposure groups: low (less than 3 micrograms per deciliter), medium (6 to 7 micrograms per deciliter), or high (greater than or equal to 10 micrograms per deciliter). Development was assessed semiannually, beginning at the age of six months, with use of the Mental Development Index of the Bayley Scales of Infant Development (mean +/- SD, 100 +/- 16). Capillary-blood samples obtained at the same times provided measures of postnatal lead exposure. Regression methods for longitudinal data were used to evaluate the association between infants' lead levels and their development scores after adjustment for potential confounders. At all ages, infants in the high-prenatal-exposure group scored lower than infants in the other two groups. The estimated difference between the overall performance of the low-exposure and high-exposure groups was 4.8 points (95 percent confidence interval, 2.3 to 7.3). Between the medium- and high-exposure groups, the estimated difference was 3.8 points (95 percent confidence interval, 1.3 to 6.3). Scores were not related to infants' postnatal blood lead levels. It appears that the fetus may be adversely affected at blood lead concentrations well below 25 micrograms per deciliter, the level currently defined by the Centers for Disease Control as the highest acceptable level for young children.

  11. Impact of colostrum and plasma immunoglobulin intake on hippocampus structure during early postnatal development in pigs.

    PubMed

    Pierzynowski, Stefan; Ushakova, Galyna; Kovalenko, Tatiana; Osadchenko, Iryna; Goncharova, Kateryna; Gustavsson, Per; Prykhodko, Olena; Wolinski, Jarek; Slupecka, Monika; Ochniewicz, Piotr; Weström, Björn; Skibo, Galina

    2014-06-01

    The first milk, colostrum, is an important source of nutrients and an exclusive source of immunoglobulins (Ig), essential for the growth and protection from infection of newborn pigs. Colostrum intake has also been shown to affect the vitality and behaviour of neonatal pigs. The objective of this study was to evaluate the effects of feeding colostrum and plasma immunoglobulin on brain development in neonatal pigs. Positive correlations were found between growth, levels of total protein and IgG in blood plasma and hippocampus development in sow-reared piglets during the first 3 postnatal days. In piglets fed an elemental diet (ED) for 24h, a reduced body weight, a lower plasma protein level and a decreased level of astrocyte specific protein in the hippocampus was observed, as compared to those that were sow-reared. The latter was coincident with a reduced microgliogenesis and an essentially diminished number of neurons in the CA1 area of the hippocampus after 72h. Supplementation of the ED with purified plasma Ig, improved the gliogenesis and supported the trophic and immune status of the hippocampus. The data obtained indicate that the development of the hippocampus structure is improved by colostrum or an Ig-supplemented elemental diet in order to stimulate brain protein synthesis and its development during the early postnatal period.

  12. Altered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid

    PubMed Central

    Furnari, Melody A.; Saw, Constance Lay-Lay; Kong, Ah-Ng; Wagner, George C

    2015-01-01

    Early exposure to valproic acid results in autism-like neural and behavioral deficits in humans and other animals through oxidative stress-induced neural damage. In the present study, valproic acid was administered to genetically altered mice lacking the Nrf2 (nuclear factor-erythroid 2 related factor 2) gene on postnatal day 14 (P14). Nrf2 is a transcription factor that induces genes that protect against oxidative stress. It was found that valproic acid-treated Nrf2 knockout mice were less active in open field activity chambers, less successful on the rotorod, and had deficits in learning and memory in the Morris water maze compared to the valproic acid-treated wild type mice. Given these results, it appears that Nrf2 knockout mice were more sensitive to the neural damage caused by valproic acid administered during early development. PMID:25454122

  13. Altered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid.

    PubMed

    Furnari, Melody A; Saw, Constance Lay-Lay; Kong, Ah-Ng; Wagner, George C

    2014-10-01

    Early exposure to valproic acid results in autism-like neural and behavioral deficits in humans and other animals through oxidative stress-induced neural damage. In the present study, valproic acid was administered to genetically altered mice lacking the Nrf2 (nuclear factor-erythroid 2 related factor 2) gene on postnatal day 14 (P14). Nrf2 is a transcription factor that induces genes that protect against oxidative stress. It was found that valproic acid-treated Nrf2 knockout mice were less active in open field activity chambers, less successful on the rotorod, and had deficits in learning and memory in the Morris water maze compared to the valproic acid-treated wild type mice. Given these results, it appears that Nrf2 knockout mice were more sensitive to the neural damage caused by valproic acid administered during early development. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Sensory Neural Responses to Ozone Exposure during Early Postnatal Development in Rat Airways

    PubMed Central

    Hunter, Dawn D.; Wu, Zhongxin; Dey, Richard D.

    2010-01-01

    Airway infections or irritant exposures during early postnatal periods may contribute to the onset of childhood asthma. The purpose of this study was to examine critical periods of postnatal airway development during which ozone (O3) exposure leads to heightened neural responses. Rats were exposed to O3 (2 ppm) or filtered air for 1 hour on specific postnatal days (PDs) between PD1 and PD29, and killed 24 hours after exposure. In a second experiment, rats were exposed to O3 on PD2–PD6, inside a proposed critical period of development, or on PD19–PD23, outside the critical period. Both groups were re-exposed to O3 on PD28, and killed 24 hours later. Airways were removed, fixed, and prepared for substance P (SP) immunocytochemistry. SP nerve fiber density (NFD) in control extrapulmonary (EXP) epithelium/lamina propria (EPLP) increased threefold, from 1% to 3.3% from PD1–PD3 through PD13–PD15, and maintained through PD29. Upon O3 exposure, SP-NFD in EXP–smooth muscle (SM) and intrapulmonary (INT)-SM increased at least twofold at PD1–PD3 through PD13–PD15 in comparison to air exposure. No change was observed at PD21–PD22 or PD28–PD29. In critical period studies, SP-NFD in the INT-SM and EXP-SM of the PD2–PD6 O3 group re-exposed to O3 on PD28 was significantly higher than that of the group exposed at PD19–PD23 and re-exposed at PD28. These findings suggest that O3-mediated changes in sensory innervation of SM are more responsive during earlier postnatal development. Enhanced responsiveness of airway sensory nerves may be a contributing mechanism of increased susceptibility to environmental exposures observed in human infants and children. PMID:20118220

  15. Neuronal nitric oxide synthase immunoreactivity in ependymal cells during early postnatal development.

    PubMed

    Soygüder, Zafer; Karadağ, Hüseyin; Nazli, Mümtaz

    2004-03-01

    Neuronal nitric oxide synthase (nNOS) immunoreactivity was observed in ependymal cell layer of the central canal of spinal cord of neonatal rats (2-20 days old). Neuronal nitric oxide synthase immunoreactivity was present in postnatal day 2 and this immunoreactivity gradually disappeared by postnatal day 16. The progressive decrease in nNOS staining with the increasing postnatal age may suggest that nNOS staining paralleled the maturation of the central canal and may also suggest that nNOS activity plays a role in the development of the ependymal cells.

  16. Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth.

    PubMed

    Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

    2013-02-01

    We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4-7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4-7 years, as well as height and head circumference at 4-7 years of age, were the exposure variables. Z-scores of weight at 4-7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child's IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4-18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18-2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06-0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4-7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth measures were associated with IQ or

  17. Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth

    PubMed Central

    Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

    2013-01-01

    Background We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4–7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4–7 years, as well as height and head circumference at 4–7 years of age, were the exposure variables. Z-scores of weight at 4–7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child’s IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4–18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Results Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18–2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06–0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4–7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth

  18. Steroid regulation of early postnatal development in the corpus epididymidis of pigs.

    PubMed

    Katleba, Kimberley D; Legacki, Erin L; Conley, Alan J; Berger, Trish

    2015-06-01

    Development of the epididymis including blood-epididymal barrier formation is not required until sperm reach the epididymis peripuberally. Regulation of this development in the early postnatal period is largely unknown. The current objectives were to evaluate potential roles of endogenous estrogen and androgen signaling during early development of the corpus epididymidis and to determine the timing of formation of the blood-epididymal barrier in the pig. Effects of endogenous steroids were evaluated using littermates treated with vehicle, an aromatase inhibitor (letrozole) to reduce endogenous estrogens, an estrogen receptor antagonist (fulvestrant) or an androgen receptor antagonist (flutamide). Phosphorylated histone 3 immunohistochemistry was used to identify proliferating epithelial cells. Lanthanum nitrate and electron microscopy were used to analyze formation of the blood barrier in the corpus epididymidis. Reducing endogenous estrogens increased the number of proliferating corpus epithelial cells at 6 and 6.5 weeks of age compared with vehicle-treated boars (P<0.01 and P<0.001 respectively). Blocking androgen receptors did not alter proliferation rate at 6.5 weeks of age. Although barrier formation was similar between 6 and 6.5 weeks of age in vehicle-treated animals, intercellular barriers increased in letrozole-treated littermates at 6.5 weeks of age. Fulvestrant treatment, which should mimic aromatase inhibition for regulation through ESR1 and ESR2 signaling but potentially stimulate endogenous estrogen signaling through the G protein-coupled estrogen receptor (GPER), had the opposite effect on aromatase inhibition. These responses in conjunction with the presence of GPER in the corpus epididymidis suggest early corpus epididymal development is regulated partially by GPER.

  19. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota.

    PubMed

    Tanaka, Shigemitsu; Kobayashi, Takako; Songjinda, Prapa; Tateyama, Atsushi; Tsubouchi, Mina; Kiyohara, Chikako; Shirakawa, Taro; Sonomoto, Kenji; Nakayama, Jiro

    2009-06-01

    The influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota was monitored in 26 infants including five antibiotic-treated (AT) subjects orally administered a broad-spectrum antibiotic for the first 4 days of life and three caesarean-delivered (CD) subjects whose mothers were intravenously injected by the similar type of antibiotics in the same period. The faecal bacterial composition was analysed daily for the first 5 days and monthly for the first 2 months. Terminal restriction fragment length polymorphisms in the AT subjects showed less diversity with the attenuation of the colonization of some bacterial groups, especially in Bifidobacterium and unusual colonization of Enterococcus in the first week than the control antibiotic-free infants (AF, n=18). Quantitative real-time PCR showed overgrowth of enterococci (day 3, P=0.01; day 5, P=0.003; month 1, P=0.01) and arrested growth of Bifidobacterium (day 3, P=0.03) in the AT group. Furthermore, after 1 month, the Enterobacteriaceae population was markedly higher in the AT group than in the AF group (month 1, P=0.02; month 2, P=0.02). CD infants sustained similar, although relatively weaker, alteration in the developing microbiota. These results indicate that antibiotic exposure at the beginning of life greatly influences the development of neonatal intestinal microbiota.

  20. Lipofuscin-like pigments in the rat heart during early postnatal development: effect of selenium supplementation.

    PubMed

    Ošťádalová, I; Charvátová, Z; Wilhelm, J

    2010-01-01

    The aim of the study was to characterize a) the lipofuscin-like pigment (LFP) accumulation (an indicator of ROS production) in the rat heart during early postnatal period and b) possible antioxidative role of selenium. Experimental animals received Na(2)SeO(3) in drinking water during gravidity and up to day 15 post partum. Two fluorophores of LFP in the hearts of 1-, 4-, 7- and 15-day-old rats were evaluated by fluorescent analysis. The highest level of heart/body weight ratio in control rats was observed on day 4, in the Se-supplemented rats on day 7. Cardiac LFP content in controls increased from postnatal day 4, in the hearts of Se-supplemented rats the LFP content increased already from day 1. As compared with the Se-supplemented group the LFP content of control hearts was significantly higher on day 1 but significantly lower on day 4. LFP concentration in control hearts decreased from postnatal day 1 to 4; this decrease was followed by significant increase until day 7 and decrease to day 15. LFP concentration in the Se-supplemented hearts was the highest on postnatal day 7; it differed from controls on day 1 and 4. Significant changes of LFP suggest an important role of ROS during critical ontogenetic period.

  1. Nitrergic neurons during early postnatal development of the prefrontal cortex in the rat: histochemical study.

    PubMed

    Hvizdosova, Natalia; Tomasova, Lenka; Bolekova, Adriana; Kolesar, Dalibor; Kluchova, Darina

    2014-06-01

    The presence of nitrergic cells in the prefrontal cortex has been confirmed, however little is known about the postnatal development of these cells. Nitrergic neurons were studied histochemically by using NADPH-diaphorase staining in the prefrontal cortex of male Wistar rats from postnatal day 7-21 (P7-21). Neuronal NADPH-diaphorase is a nitric oxide synthase that provides a specific histochemical marker for neurons producing nitric oxide (NO). NO acts as a neurotransmitter and intracellular signaling molecule in the nervous system. We observed in 7 day old rats NADPH-d containing neurons that were intensely stained. These neurons were bipolar with a short dendrite with average length of 23 μm. During the second postnatal week, the neurons were mainly bipolar and were rarely multipolar. By P14 the cells were located primarily in cortical layers III-VI. Nitrergic neurons of the 21 day old rats were histochemically identified as multipolar cells with long radial extending dendrites. Dendrites of neurons in 14 and 21 day old rats were a similar length with an average of 57 μm. These results suggest that nitrergic neurons differentiate during a relatively short period of time and reach their structural maturity by the end of the second week of postnatal development.

  2. Effect of early postnatal air-conduction auditory deprivation on the development and function of the rat spiral ganglion.

    PubMed

    Wang, F; Gao, X; Chen, J; Liu, S-L; Wang, F-Y; Hei, R-Y; Chen, Y; Qiu, J-H

    2011-09-01

    To evaluate the effect of early postnatal air-conduction auditory deprivation on the development and function of the rat spiral ganglion. Randomised animal study. Sixty neonatal Sprague-Dawley rats were randomly divided into two groups: controls (n = 30) given regular chow and water ad libitum; and study animals (n = 30) fed within a soundproof chamber. Auditory brainstem response testing was conducted in both groups on postnatal day 42. Auditory deprivation between postnatal days 12 and 42 resulted in an increased hearing threshold and reduced auditory brainstem response amplitudes, together with degeneration of type I spiral ganglion neurons and the presence of apoptotic cells. Non-invasive auditory deprivation during a critical developmental period resulted in numerous changes in rat cochlear function and morphology.

  3. A functional requirement for astroglia in promoting blood vessel development in the early postnatal brain.

    PubMed

    Ma, Shang; Kwon, Hyo Jun; Huang, Zhen

    2012-01-01

    Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net decreases in vessel density between different stages after normalizing for cortical expansion nor obvious apoptosis of endothelial cells in these mutants. Furthermore, concomitant with loss of astroglial interactions, we find increased endothelial cell proliferation, enlarged vessel luminal size as well as enhanced cytoskeletal gene expression in pericytes, which suggests compensatory changes in vascular cells. Lastly, we find that blood vessel morphology in mutant cortices recovers substantially at later stages, following astrogliosis. These results thus implicate a functional requirement for astroglia in promoting blood vessel growth during brain development.

  4. A Functional Requirement for Astroglia in Promoting Blood Vessel Development in the Early Postnatal Brain

    PubMed Central

    Ma, Shang; Kwon, Hyo Jun; Huang, Zhen

    2012-01-01

    Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net decreases in vessel density between different stages after normalizing for cortical expansion nor obvious apoptosis of endothelial cells in these mutants. Furthermore, concomitant with loss of astroglial interactions, we find increased endothelial cell proliferation, enlarged vessel luminal size as well as enhanced cytoskeletal gene expression in pericytes, which suggests compensatory changes in vascular cells. Lastly, we find that blood vessel morphology in mutant cortices recovers substantially at later stages, following astrogliosis. These results thus implicate a functional requirement for astroglia in promoting blood vessel growth during brain development. PMID:23110156

  5. Early postnatal exposure to endosulfan interferes with the normal development of the male rat mammary gland.

    PubMed

    Altamirano, Gabriela A; Delconte, Melisa B; Gomez, Ayelen L; Alarcón, Ramiro; Bosquiazzo, Verónica L; Luque, Enrique H; Muñoz-de-Toro, Mónica; Kass, Laura

    2017-09-19

    Our aim was to evaluate whether postnatal exposure to endosulfan (ENDO) modifies mammary gland (MG) development in pre- and post-pubertal male rats. From postnatal day 1 (PND1) to PND7, male rats were injected subcutaneously every 48h with either corn oil (vehicle) or 600μg ENDO/kg.bw. On PND21 and PND60, MG and blood samples were collected. Estradiol (E2) and testosterone (T) serum levels, MG histology, collagen fiber organization, proliferation index, and estrogen (ESR1) and androgen receptor (AR) expressions were evaluated. On PND21, E2 and T levels were similar between groups, whereas MG area, perimeter, number of terminal end buds and ESR1 expression were increased in ENDO-exposed rats. These changes were associated with alveolar development and increased organized collagen in the stroma. On PND60, a higher proliferation index in ENDO-exposed rats was correlated with a more developed lobuloalveolar structure. Hyperplastic alveoli and, hyperplastic ducts surrounded by a dense stroma were also observed in this group. T levels and ESR1 expression were similar between groups, whereas E2 levels and AR expression were decreased in ENDO-exposed rats. The exposure to ENDO in the first week of life interferes with the normal development of the MG and induces pre-malignant lesions in post-pubertal male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

    PubMed Central

    2010-01-01

    Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA) and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism. PMID:20723245

  7. Expression of klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood.

    PubMed

    Clinton, Sarah M; Glover, Matthew E; Maltare, Astha; Laszczyk, Ann M; Mehi, Stephen J; Simmons, Rebecca K; King, Gwendalyn D

    2013-08-21

    Without the age-regulating protein klotho, mouse lifespan is shortened and the rapid onset of age-related disorders occurs. Conversely, overexpression of klotho extends mouse lifespan. Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus. Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development. We used in situ hybridization to map klotho mRNA expression in the developing and adult rat brain and report moderate, widespread expression across grey matter regions. mRNA expression levels in cortex, hippocampus, caudate putamen, and amygdala decreased during the second week of life and then gradually rose to adult levels by postnatal day 21. Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain. Klotho protein co-localized with both the neuronal marker NeuN, as well as, oligodendrocyte marker olig2. These results provide the first anatomical localization of klotho mRNA and protein in rat brain parenchyma and demonstrate that klotho levels vary during early postnatal development.

  8. [Effect of perinatal factors on postnatal development of lymphocyte subsets in early preterm infants].

    PubMed

    Zhou, Ping; Chen, Rui; Zou, Cai-Yan; Zhang, Min; Chen, Zhao-Hong; Ma, Li-Ya

    2016-10-01

    To study the postnatal changes in lymphocyte subsets in early preterm infants and the effect of perinatal factors on lymphocyte subsets. A total of 61 early preterm infants were enrolled. Flow cytometry was used to measure the absolute counts of lymphocytes and lymphocyte subsets at 1, 7, 14, and 28 days after birth, as well as at 6 months after birth for 17 of these early preterm infants. The effects of perinatal factors, such as antepartum use of hormone, intrauterine infection, gestational age at birth, and Ureaplasma urealyticum (UU) colonization, on lymphocyte subsets were analyzed. The absolute counts of lymphocyte subsets except natural killer (NK) cells were lowest at birth, increased rapidly at 1 week after birth, and reached the levels in healthy infants at 6 months; the count of NK cells remained at a low level and increased significantly at 6 months after birth. Compared with those with a gestational age of <28 weeks, the early preterm infants with a gestational age of ≥28 weeks had significantly higher absolute counts of T cells, T helper (Th) cells, and NK cells at 7 days after birth, a significantly higher absolute count of T cells at 14 days after birth, and significantly higher absolute counts of lymphocytes and Th cells at 28 days after birth (P<0.05). Compared with the group not using hormone, the group using hormone showed a significantly higher absolute count of T cells at 7 days after birth and significantly higher absolute counts of lymphocytes and all subsets at 14 days after birth (P<0.05). There was no significant difference in lymphocyte subsets at 1 day after birth between the intrauterine infection and non-infection groups (P>0.05); the intrauterine infection group had significantly higher absolute counts of B cells at 7 and 14 days after birth than the non-infection group. Compared those without UU colonization, the infants with UU colonization had significantly higher absolute counts of lymphocytes, T cells, Th cells, and Ts cells

  9. The effect of colostrum ingestion during the first 24 hours of life on early postnatal development of piglet immune systems.

    PubMed

    Ogawa, Shohei; Tsukahara, Takamitsu; Imaoka, Taishi; Nakanishi, Nobuo; Ushida, Kazunari; Inoue, Ryo

    2016-12-01

    It has been suggested that colostrum is important not only for direct protection from pathogens but also for proper development of immune systems in piglets. In this study, we focused on the effect of colostrum ingestion during the first 24 h of life on early postnatal development of piglet immune systems. Thirty-six piglets from five litters were divided into colostrum-fed (CoF) and colostrum-deprived (CoD) groups. The former group was allowed to suckle normally while formula milk was fed to the latter group during the first 24 h of life. At the weaning period, the concentrations of fecal immunoglobulin (Ig) A and plasma IgG as well as the number of blood leukocyte subsets were analyzed. Fecal IgA and plasma IgG concentrations in the CoF group were more than twice as high as those in the CoD group (P < 0.01). In addition, the number of blood B cells was significantly higher in the CoF group than that in the CoD group (P < 0.05). This study demonstrates that colostrum ingestion during the first 24 h plays a significant role in early postnatal development of both mucosal and systemic immunity of piglets.

  10. [Melanotropic activity in the hypophysis and blood of Wistar rats in early postnatal development].

    PubMed

    Panova, I G; Sologub, A A; Burlakova, O V; Stroeva, O G

    1993-01-01

    The activity of melanotropins in pituitary homogenates and blood of Wistar rats obtained from the nursery Stolbovaia (Russian Academy of Medical Sciences) was studied using the method of biological testing (Hogben, Slome, 1931; Golichenkov, 1980). In order to elucidate, to what extent the normal status of melanotropic activity is retained in albino rats, two experimental series were performed. Melanotropic activity was determined in (1) intact rats and (2) in rats receiving subcutaneous injections of parachlorophenylalanine, a specific inhibitor of serotonin synthesis. Melanotropic activity of Wistar rats hypophysis during the studied period of development was similar to that of normal pigmented rats. However, the peak of melanotropic activity of blood which is characteristically observed in pigmented rats on day 3 of postnatal development is absent in the case of Wistar rats. The experimentally induced decrease in the serotonin level did not result in the increased melanotropic activity of blood. These data suggest that certain structures of hypophysis responsible for MSH secretion can be disturbed in Wistar rats. A short-term peak of blood MSH in rats during the first week after birth is known to provide for maturation of dopaminergic neurons located in the arcuate nucleus of the hypothalamus. Consequently, the absence of such peak in Wistar rats should result in neuroendocrine disturbances such as inadequate functioning of dopaminergic neurons responsible for melanotropin secretion by hypophysis beginning from the second week after birth (Lichtensteiger, Schlumpf, 1986).

  11. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    PubMed

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O2, 6 h; postnatal day 7, P7) at P14. Exposure to hypoxia led to reduced body weight (P < 0.001) and length (P < 0.04) compared with controls and was associated with significantly reduced plasma levels of mouse GH (P < 0.01) and IGF-1 (P < 0.01). RhGH abrogated these hypoxia-induced changes of the GH/IGF-1 axis associated with normalization of weight and length gain until P14 compared with controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain.

  12. Expression of Glucocorticoid Receptor and Early Growth Response Gene 1 during Postnatal Development of Two Inbred Strains of Mice Exposed to Early Life Stress

    PubMed Central

    Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

    2010-01-01

    Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

  13. Early postnatal migration and development of layer II pyramidal neurons in the rodent cingulate/retrosplenial cortex.

    PubMed

    Zgraggen, Eloisa; Boitard, Michael; Roman, Inge; Kanemitsu, Michiko; Potter, Gael; Salmon, Patrick; Vutskits, Laszlo; Dayer, Alexandre G; Kiss, Jozsef Z

    2012-01-01

    The cingulate and retrosplenial regions are major components of the dorsomedial (dm) limbic cortex and have been implicated in a range of cognitive functions such as emotion, attention, and spatial memory. While the structure and connectivity of these cortices are well characterized, little is known about their development. Notably, the timing and mode of migration that govern the appropriate positioning of late-born neurons remain unknown. Here, we analyzed migratory events during the early postnatal period from ventricular/subventricular zone (VZ/SVZ) to the cerebral cortex by transducing neuronal precursors in the VZ/SVZ of newborn rats/mice with Tomato/green fluorescent protein-encoding lentivectors. We have identified a pool of postmitotic pyramidal precursors in the dm part of the neonatal VZ/SVZ that migrate into the medial limbic cortex during the first postnatal week. Time-lapse imaging demonstrates that these cells migrate on radial glial fibers by locomotion and display morphological and behavioral changes as they travel through the white matter and enter into the cortical gray matter. In the granular retrosplenial cortex, these cells give rise to a Satb2+ pyramidal subtype and develop dendritic bundles in layer I. Our observations provide the first insight into the patterns and dynamics of cell migration into the medial limbic cortex.

  14. Localization of FGF-6 and FGFR-4 during prenatal and early postnatal development of the mouse sublingual gland.

    PubMed

    Uehara, Toshitomo

    2006-03-01

    A number of fibroblast growth factors (FGFs) are involved in regulatory mechanisms of the salivary gland development. However, the role of FGF-6 unique in myogenic cells has not been elucidated in the developing sublingual gland. In the present study, temporo-spatial expression of FGF-6 and its receptor (FGFR)-4, in conjunction with some related histo-chemical properties, were investigated in the sublingual gland of the prenatal and early postnatal mice. The earliest expression of both FGF-6 and FGFR-4 was detected in immature acinar cells at gestational day 17 (GD17). The staining intensity increased gradually and some acinar cells showed a distinct staining at postnatal day 0 (PD0). The immunopositive cells had a relatively round profile and were assumed to be acinar cells. The positive staining decreased thereafter and disappeared completely by PD11. To confirm the identity of cells positive for FGF-6, double immunolabeling with anti-alphasmooth muscle actin (alphaSMA) and anti-FGF-6 antibodies was performed. The positive staining of alphaSMA, a marker of myoepithelial cells, was detected in the flattened cells surrounding the acini but not in the cells positive for FGF-6. The staining properties of secretory granules in acinar cells were also examined with periodic acid-Shiff (PAS) and alcian blue (AB). PAS-positive granules abundant in the late gestational stages (GD17 to PD0) began to be replaced with AB-positive mucous granules at early neonatal days (PD0-3), when the FGF-6/FGFR-4 expression was the strongest. These findings suggest that FGF-6/FGFR-4 might be involved in the changes of secretory granule content of acinar cells in the sublingual gland during the late gestational and early neonatal stages.

  15. Role of tonic GABAergic currents during pre- and early postnatal rodent development

    PubMed Central

    Kilb, Werner; Kirischuk, Sergei; Luhmann, Heiko J.

    2013-01-01

    In the last three decades it became evident that the GABAergic system plays an essential role for the development of the central nervous system, by influencing the proliferation of neuronal precursors, neuronal migration and differentiation, as well as by controlling early activity patterns and thus formation of neuronal networks. GABA controls neuronal development via depolarizing membrane responses upon activation of ionotropic GABA receptors. However, many of these effects occur before the onset of synaptic GABAergic activity and thus require the presence of extrasynaptic tonic currents in neuronal precursors and immature neurons. This review summarizes our current knowledge about the role of tonic GABAergic currents during early brain development. In this review we compare the temporal sequence of the expression and functional relevance of different GABA receptor subunits, GABA synthesizing enzymes and GABA transporters. We also refer to other possible endogenous agonists of GABAA receptors. In addition, we describe functional consequences mediated by the GABAergic system during early developmental periods and discuss current models about the origin of extrasynaptic GABA and/or other endogenous GABAergic agonists during early developmental states. Finally, we present evidence that tonic GABAergic activity is also critically involved in the generation of physiological as well as pathophysiological activity patterns before and after the establishment of functional GABAergic synaptic connections. PMID:24027498

  16. Reduced densities of parvalbumin- and somatostatin-expressing interneurons in experimental cortical dysplasia and heterotopia in early postnatal development.

    PubMed

    Akakin, Dilek; Martinez-Diaz, Hildabelis; Chen, Huan-Xin; Roper, Steven N

    2013-05-01

    Cortical dysplasia (CD) is strongly associated with intractable epilepsy, probably due to hyperexcitability of neuronal networks. However, the underlying mechanisms are not completely understood. GABAergic interneurons provide major inhibitory function in the CNS and have different subtypes, but it is not clear how each subtype is affected in CD during early post-natal development. We have examined the developmental alterations of the densities of two major subtypes of interneurons, parvalbumin (PV)- and somatostatin (SS)-expressing interneurons in an animal model of CD, in utero irradiation, using immunocytochemistry. We found that the density of PV- and SS-positive interneurons increases significantly in CD and controls during the first three weeks of postnatal life. However, compared to controls, the densities of both subtypes are significantly decreased in CD and heterotopia at all age groups although the time of onset for both PV and SS expression remained unchanged. Our results indicate that the densities of both PV- and SS-positive interneurons are significantly decreased in CD and heterotopia, which may be one important mechanism leading to hyperexcitability of CD.

  17. Transient overexposure of neuregulin 3 during early postnatal development impacts selective behaviors in adulthood.

    PubMed

    Paterson, Clare; Law, Amanda J

    2014-01-01

    Neuregulin 3 (NRG3), a specific ligand for ErbB4 and a neuronal-enriched neurotrophin is implicated in the genetic predisposition to a broad spectrum of neurodevelopmental, neurocognitive and neuropsychiatric disorders, including Alzheimer's disease, autism and schizophrenia. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, accompanied by increased expression of prefrontal cortical NRG3. Despite our expanding knowledge of genetic involvement of NRG3 in neurological disorders, little is known about the neurodevelopmental mechanisms of risk. Here we exploited the fact that a paralog of NRG3, NRG1, readily penetrates the murine blood brain barrier (BBB). In this study we synthesized the bioactive epidermal growth factor (EGF) domain of NRG3, and using previously validated in-vivo peripheral injection methodologies in neonatal mice, demonstrate that NRG3 successfully crosses the BBB, where it activates its receptor ErbB4 and downstream Akt signaling at levels of bioactivity comparable to NRG1. To determine the impact of NRG3 overexpression during one critical developmental window, C57BL/6 male mice were subcutaneously injected daily with NRG1-EGF, NRG3-EGF or vehicle from postnatal days 2-10. Mice were tested in adulthood using a comprehensive battery of behavioral tasks relevant to neurocognitive and psychiatric disorders. In agreement with previous studies, developmental overexposure to NRG1 induced multiple non-CNS mediated peripheral effects as well as severely disrupting performance of prepulse inhibition of the startle response. In contrast, NRG3 had no effect on any peripheral measures investigated or sensorimotor gating. Specifically, developmental NRG3 overexposure produced an anxiogenic-like phenotype and deficits in social behavior in adulthood. These results provide primary data to support a role for NRG3 in brain development and function, which appears to be distinct from

  18. Transient Overexposure of Neuregulin 3 during Early Postnatal Development Impacts Selective Behaviors in Adulthood

    PubMed Central

    Paterson, Clare; Law, Amanda J.

    2014-01-01

    Neuregulin 3 (NRG3), a specific ligand for ErbB4 and a neuronal-enriched neurotrophin is implicated in the genetic predisposition to a broad spectrum of neurodevelopmental, neurocognitive and neuropsychiatric disorders, including Alzheimer's disease, autism and schizophrenia. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, accompanied by increased expression of prefrontal cortical NRG3. Despite our expanding knowledge of genetic involvement of NRG3 in neurological disorders, little is known about the neurodevelopmental mechanisms of risk. Here we exploited the fact that a paralog of NRG3, NRG1, readily penetrates the murine blood brain barrier (BBB). In this study we synthesized the bioactive epidermal growth factor (EGF) domain of NRG3, and using previously validated in-vivo peripheral injection methodologies in neonatal mice, demonstrate that NRG3 successfully crosses the BBB, where it activates its receptor ErbB4 and downstream Akt signaling at levels of bioactivity comparable to NRG1. To determine the impact of NRG3 overexpression during one critical developmental window, C57BL/6 male mice were subcutaneously injected daily with NRG1-EGF, NRG3-EGF or vehicle from postnatal days 2–10. Mice were tested in adulthood using a comprehensive battery of behavioral tasks relevant to neurocognitive and psychiatric disorders. In agreement with previous studies, developmental overexposure to NRG1 induced multiple non-CNS mediated peripheral effects as well as severely disrupting performance of prepulse inhibition of the startle response. In contrast, NRG3 had no effect on any peripheral measures investigated or sensorimotor gating. Specifically, developmental NRG3 overexposure produced an anxiogenic-like phenotype and deficits in social behavior in adulthood. These results provide primary data to support a role for NRG3 in brain development and function, which appears to be distinct

  19. Darkness during early postnatal development is required for normal circadian patterns in the adult rat.

    PubMed

    Cambras, T; Canal, M M; Cernuda-Cernuda, R; García-Fernández, J M; Díez-Noguera, A

    2015-03-01

    Early light experience influences the brain during development. Perinatal light exposure has an important effect on the development of the circadian system, although the role of quantity versus quality of light in this process is still unclear. We tested the development of the circadian rhythm of locomotor activity under constant bright light from the day of weaning, of six groups of rats raised under different light conditions during suckling. Results indicated that when rats received daily darkness during suckling (rats reared under constant darkness or light-dark cycles with dim or bright light) became arrhythmic when exposed to continuous bright light after weaning. However, those rats reared in the absence of darkness (constant dim or bright light, or alternating dim and bright light) developed a circadian rhythm, which was stronger and had a shorter period depending on the quantity of light received during suckling. Vasointestinal polypeptide immunoreactivity in the suprachiasmatic nucleus (SCN) was higher in those rats with weaker rhythms. However, no apparent differences among these groups were found in the melanopsin-expressing retinal ganglion cells, which provide the SCN with light input in the photoentrainment process. When bright light was shifted to dim light in three of the groups on day 57 after weaning, all of them generated a circadian rhythm with a longer period in those rats previously arrhythmic. Our results indicate the importance of the amount of light received at the early stages of life in the development of the circadian system and suggest that darkness is needed for the normal development of circadian behaviour.

  20. Morphological and functional changes in the spleen of mice offspring at different stages of postnatal development after a single immunostimulating impact on maternal organism in early pregnancy.

    PubMed

    Yaglova, N V; Obernikhin, S S

    2014-02-01

    We studied the effect of short-term activation of the maternal immune system with T-cell mitogen concanavalin A at the early terms of pregnancy on the postnatal development of the spleen in the offspring. It was found that single immunostimulatory exposure prior to the formation of the fetal immune system delays the postnatal development of the spleen until the beginning of puberty and impairs the formation of splenic lymphatic nodules with the predominant development of germinal centers as well as increases the number of mast cells in this organ.

  1. Effects of dust, formaldehyde and delayed feeding on early postnatal development of broiler chickens.

    PubMed

    de Gouw, Pieter; van de Ven, Lotte J F; Lourens, Sander; Kemp, Bas; van den Brand, Henry

    2017-06-01

    We investigated effects of perinatal exposure to dust or formaldehyde and the moment of first feed intake after hatching on broiler chicken development during the first week of life. Four environmental treatments were used from 468 until 512h of incubation: control (CONT), heat treated dust (HTD), untreated dust (UTD) or formaldehyde disinfection (FORM). After hatching, all chickens were assigned to 1 of 2 feeding treatments: early feeding (EF; feed and water available in the hatcher) or delayed feeding (DF). After 512h of incubation (day 0), chickens were reared until day 7 of age. In DF chickens, body weight (BW), yolk free body mass (YFBM) and relative liver weight did not differ among environmental treatments at day 0. However, in EF chickens BW at day 0 was greater in HTD chickens than in UTD and FORM chickens. YFBM in EF chickens at day 0 was greater when chickens were exposed to HTD compared to the other environmental treatments. In EF chickens, relative liver weight was greater in HTD chickens than in FORM. In DF chickens, BW at day 0 was positively related with hatching time (HT). In EF chickens, YFBM was positively related to HT. Residual yolk weight at day 0 was positively related with HT, whereas relative liver weight and microbicidal capacity were negatively related with HT. This study demonstrated that formaldehyde and dust during the hatching phase affect broiler chicken development at pulling from the incubator, but not at day 7. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood.

    PubMed

    Oosting, Annemarie; van Vlies, Naomi; Kegler, Diane; Schipper, Lidewij; Abrahamse-Berkeveld, Marieke; Ringler, Silvia; Verkade, Henkjan J; van der Beek, Eline M

    2014-01-28

    Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has been shown to be protective against obesity, and we have previously shown in mice that the physical structure of lipids in human milk may contribute to this protective effect. In the present study, we investigated how differences in the physical structure of lipids in the early diet may modulate adipose tissue development. Male mice were fed a diet containing control infant milk formula (Control IMF; Danone Research) or Nuturis® (Concept IMF with large phospholipid-coated lipid droplets; Danone Research) from postnatal day (PN)16 to 42. Subsequently, mice were challenged with a moderate Western-style diet (WSD) until PN98, and body composition was monitored by dual-energy X-ray absorptiometry. Epididymal WAT was analysed for adipocyte size, number and gene expression of metabolic transcription factors. Early Concept IMF exposure reduced fat accumulation during the WSD challenge by 30 % compared with the Control IMF. It reduced adipocyte size without affecting adipocyte number in adult mice. The Concept IMF decreased the expression of PPARγ, CCAAT/enhancer-binding protein and retinoid X receptor α in WAT in adulthood, key regulators of metabolic activity. In conclusion, Concept IMF exposure in early life reduced susceptibility to obesity in adult life, by preventing adipocyte hypertrophia upon adult dietary challenge without affecting adipogenesis. These data emphasise the importance of the physical properties of dietary lipids in early life in obesity risk later in life.

  3. Functional role of ambient GABA in refining neuronal circuits early in postnatal development

    PubMed Central

    Cellot, Giada; Cherubini, Enrico

    2013-01-01

    Early in development, γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mature brain, depolarizes and excites targeted neurons by an outwardly directed flux of chloride, resulting from the peculiar balance between the cation-chloride importer NKCC1 and the extruder KCC2. The low expression of KCC2 at birth leads to accumulation of chloride inside the cell and to the equilibrium potential for chloride positive respect to the resting membrane potential. GABA exerts its action via synaptic and extrasynaptic GABAA receptors mediating phasic and tonic inhibition, respectively. Here, recent data on the contribution of “ambient” GABA to the refinement of neuronal circuits in the immature brain have been reviewed. In particular, we focus on the hippocampus, where, prior to the formation of conventional synapses, GABA released from growth cones and astrocytes in a calcium- and SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor)-independent way, diffuses away to activate in a paracrine fashion extrasynaptic receptors localized on distal neurons. The transient increase in intracellular calcium following the depolarizing action of GABA leads to inhibition of DNA synthesis and cell proliferation. Tonic GABA exerts also a chemotropic action on cell migration. Later on, when synapses are formed, GABA spilled out from neighboring synapses, acting mainly on extrasynaptic α5, β2, β3, and γ containing GABAA receptor subunits, provides the membrane depolarization necessary for principal cells to reach the window where intrinsic bursts are generated. These are instrumental in triggering calcium transients associated with network-driven giant depolarizing potentials which act as coincident detector signals to enhance synaptic efficacy at emerging GABAergic and glutamatergic synapses. PMID:23964205

  4. Supplementation with fish oil and coconut fat prevents prenatal stress-induced changes in early postnatal development.

    PubMed

    Borsonelo, Elizabethe C; Suchecki, Deborah; Calil, Helena Maria; Galduróz, José Carlos F

    2011-08-01

    Adequate development of the central nervous system depends on prenatal and postnatal factors. On one hand, prenatal stress (PNS) has been implicated in impaired development of the offspring. On other hand, nutritional factors during pregnancy and lactation can influence fetal and postnatal growth. This study assessed the postnatal development of rat offspring exposed to PNS, which consisted of restraint and bright lights, 3 times/day, from days 14 to 20 of pregnancy, whose mothers were fed different diets during pregnancy and lactation: regular diet, diet supplemented with coconut fat or fish oil. When pregnancy was confirmed, they were distributed into control (CTL) or PNS groups. At birth, PNS males and females weighed less than those in the group CTL. At 21 days of age, this alteration was no longer observed with fish oil and coconut fat groups. PNS and coconut fat diet induced increased locomotor activity in 13 day old male and female pups, and this effect was prevented by fish oil supplementation only in females. In conclusion, postnatal development from birth to weaning was influenced by PNS and diet and some of those alterations were prevented by coconut fat and fish oil.

  5. [Carotenoids of the human eye in prenatal and early postnatal development].

    PubMed

    Panova, I G; Stroeva, O G; Ostrovskiĭ, M A

    2013-09-01

    The review deals with the role of carotenoids in the formation of the structural and functional differentiation of the macula--the area of the highest visual acuity of the human retina. The review also presents the data on detection of carotenoids (lutein) in the vitreous body of the human eye during its prenatal development and discusses their possible role in the development of the retina, particularly in relation to differentiation of the macular area. Macular dystrophy has been considered till recently as senile pathology. According to modern ophthalmologic observations, the number of cases of appearance of this pathology increases in young humans. Such a shift can be prevented by addition of carotenoids to the diet. This permits a conclusion that the permanent presence of carotenoids in the course of the whole human life is necessary for the formation and retention of structural and functional integrity of the macula.

  6. Morphine exposure and maternal deprivation during the early postnatal period alter neuromotor development and nerve growth factor levels.

    PubMed

    de Oliveira, Carla; Scarabelot, Vanessa L; Vercelino, Rafael; Silveira, Natalia P; Adachi, Lauren N S; Regner, Gabriela G; Silva, Lisiane S; de Macedo, Isabel Cristina; de Souza, Andressa; Caumo, Wolnei; Torres, Iraci L S

    2017-09-05

    The objective of this study was to verify whether repeated morphine administration and maternal deprivation in early life alter neurobehavioral development and central nerve growth factor (NGF) levels. A total of 58 male Wistar rat pups were used in our study. From postnatal day 1 (P1), litters were daily deprived of their mother for 3h; this was continued for the first 10days of life. Animals were divided into 5 groups: total control (C), did not receive any intervention; saline (S), received saline solution; morphine (M), received morphine; deprived-saline group (DS), were subjected to maternal deprivation and received saline solution; and deprived-morphine (DM), were subjected to maternal deprivation and received morphine. From P8, newborns received subcutaneous (s.c.) injections of morphine or saline (5μg) once daily for 7days. Righting reflex, negative geotaxis and gait were chosen as postural parameters to evaluate neuromotor reflexes. In the righting reflex test, a delay in the development of animals was evidenced in the M group. Performance of negative geotaxis was slower in the M and DM groups. In the gait test, all groups showed a daily improvement in performance in terms of locomotion frequency. An increased frequency of rearing was observed in the M, DS, and DM groups from P16 to P20. The DM group presented an increase in NGF levels in the brainstem. An increase in cerebral cortex NGF levels in the M, DS, and DM groups was observed as well. Our results suggest that changes in environmental conditions and the disruption of mother-infant interactions during the neonatal period can produce changes in the neurobiology, physiology, and emotional behavior of rats. This finding has important implications for the maternal-neonate interaction needed for normal brain development in newborns. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. [2 stages in the development of spontaneous motor activity in the early postnatal ontogeny of rats].

    PubMed

    Bursian, A V; Dmitrieva, L E

    1994-01-01

    In ontogenesis of rats, similar to many other animals, in the development of the spontaneous motor activity two qualitatively different stages are observed. The first one is characterized by periodic, mainly sensor-independent generalized motor excitation which at the second stage is substituted by stereotypic specialized motor programs (locomotion, grooming). Both stages exhibit similar age dynamics: the increase in the activity, its maximum and subsequent inhibition with a shift of the corresponding phases for about two weeks. This dynamics is mainly associated with heterochronous maturation of excitatory and inhibitory systems of regulation of the nervous activity. Change in the stages depends on changes of functional role of motor activity in ontogenesis from mainly morphogenetic one (and promotion of a necessary level of vegetative functions) to directional behavior. Inhibition at the first stage results in deep functional rearrangement in the central nervous system serving as a background for the onset of specialized behavioural activity. The development of the latter is also excessive, the subsequent inhibition being less deep and reversible.

  8. Sex-related differences in spatial learning during the early postnatal development of the rat.

    PubMed

    Cimadevilla, J M; González-Pardo, H; López, L; Diaz, F; Cueto, E G; Garcia-Moreno, L M; Arias, J L

    1999-06-01

    Some authors have reported that male rats younger than 21 days old are unable to perform spatial learning correctly because they have still not developed the ability to use extra-maze cues. In experiment 1, we analyzed spatial learning in 14-, 21-, 30- and 42-day-old rats using the Morris water maze (MWM). According to our results, a good performance was observed in 30-day-old male rats whereas this was not observed in female rats until they were 42 days old. In experiment 2 we studied the role of sex hormones in this kind of learning using the MWM and 30-day-old rats (castrated male rats and female rats treated with testosterone propionate (TP) after birth). The latter group, the male control group and the castrated males all solved the task correctly. The objective of experiment 3 was to determine possible differences between the sexes in the use of taxon strategies in the T water maze. To summarize, sexual dimorphism was only observed in spatial learning during development.

  9. Dynamic Regulation of the Adenosine Kinase Gene during Early Postnatal Brain Development and Maturation

    PubMed Central

    Kiese, Katharina; Jablonski, Janos; Boison, Detlev; Kobow, Katja

    2016-01-01

    The ubiquitous metabolic intermediary and nucleoside adenosine is a “master regulator” in all living systems. Under baseline conditions adenosine kinase (ADK) is the primary enzyme for the metabolic clearance of adenosine. By regulating the availability of adenosine, ADK is a critical upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. ADK protein exists in the two isoforms nuclear ADK-L, and cytoplasmic ADK-S, which are subject to dynamic expression changes during brain development and in response to brain injury; however, gene expression changes of the Adk gene as well as regulatory mechanisms that direct the cell-type and isoform specific expression of ADK have never been investigated. Here we analyzed potential gene regulatory mechanisms that may influence Adk expression including DNA promoter methylation, histone modifications and transcription factor binding. Our data suggest binding of transcription factor SP1 to the Adk promoter influences the regulation of Adk expression. PMID:27812320

  10. Low ambient temperature during early postnatal development fails to cause a permanent induction of brown adipocytes.

    PubMed

    Chabowska-Kita, Agnieszka; Trabczynska, Anna; Korytko, Agnieszka; Kaczmarek, Monika M; Kozak, Leslie P

    2015-08-01

    The brown adipocyte phenotype (BAP) in white adipose tissue (WAT) is transiently induced in adult mammals in response to reduced ambient temperature. Since it is unknown whether a cold challenge can permanently induce brown adipocytes (BAs), we reared C57BL/6J (B6) and AxB8/PgJ (AxB8) mice at 17 or 29°C from birth to weaning, to assess the BAP in young and adult mice. Energy balance measurements showed that 17°C reduced fat mass in the preweaning mice by increasing energy expenditure and suppressed diet-induced obesity in adults. Microarray analysis of global gene expression of inguinal fat (ING) from 10-day-old (D) mice indicates that expression at 17°C vs. 29°C was not different. Between 10 and 21 days of age, the BAP was induced coincident with morphologic remodeling of ING and marked changes in expression of neural development genes (e.g., Akap 12 and Ngfr). Analyses of Ucp1 mRNA and protein showed that 17°C transiently increased the BAP in ING from 21D mice; however, BAs were unexpectedly present in mice reared at 29°C. The involution of the BAP in WAT occurred after weaning in mice reared at 23°C. Therefore, the capacity to stimulate thermogenically competent BAs in WAT is set by a temperature-independent, genetically controlled program between birth and weaning. © The Author(s).

  11. ZINC AND GLUTAMINE IMPROVE BRAIN DEVELOPMENT IN SUCKLING MICE SUBJECTED TO EARLY POST-NATAL MALNUTRITION

    PubMed Central

    Ladd, Fernando V.L.; Ladd, Aliny A.B.L.; Ribeiro, Antônio Augusto C.M.; Costa, Samuel B.C.; Coutinho, Bruna P.; Feitosa, George André S.; de Andrade, Geanne M.; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C.; Castro, Ibraim C.; Oliveira, Bruna B.; Guerrant, Richard L.; Lima, Aldo Ângelo M.; Oriá, Reinaldo B.

    2009-01-01

    Objective The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Methods Malnutrition was induced by clustering the litter size from 6–7 pups/dam (nourished control) to 12–14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40–80μl) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin (SYN) and myelin basic protein (MBP) brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Results Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal GABA and SYN levels on day 14. Conclusion We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. PMID:20371167

  12. Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition.

    PubMed

    Ladd, Fernando V L; Ladd, Aliny A B L; Ribeiro, Antônio Augusto C M; Costa, Samuel B C; Coutinho, Bruna P; Feitosa, George André S; de Andrade, Geanne M; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C; Castro, Ibraim C; Oliveira, Bruna B; Guerrant, Richard L; Lima, Aldo Angelo M; Oriá, Reinaldo B

    2010-06-01

    The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Postnatal testosterone levels and temperament in early infancy.

    PubMed

    Alexander, Gerianne M; Saenz, Janet

    2011-12-01

    Recent research showing associations between behavior and postnatal testosterone levels in male infants has suggested that the transient activation of the hypothalamic-pituitary-gonadal axis in early infancy may influence the expression of gender phenotypes in later development (i.e., the postnatal hormone hypothesis). As a further test of the relationship between postnatal hormones and behavior in infancy, we measured digit ratios and salivary testosterone in 76 male and female infants (3-4 months of age) and parents completed the Infant Behavior Questionnaire-Revised, a well-established measure of temperament in the first year of life. Consistent with our earlier findings, there were no significant sex differences in salivary testosterone levels and testosterone levels were unrelated to measures of behavior in female infants. However, in male infants, higher androgen levels predicted greater Negative Affectivity. Further examination of the four scales contributing to the measure of Negative Affectivity showed testosterone levels were a significant predictor of scores on the Distress to Limitations scale, but not of scores on Fear, Sadness, or Reactivity scales. This sex-specific association between salivary testosterone and behavior in infants is consistent with animal research showing higher prenatal androgens associated with typical male development lower the threshold of sensitivity to endogenous testosterone in postnatal life. In sum, these data provide additional support for the postnatal hormone hypothesis and suggest postnatal testosterone levels may influence the development of emotional regulation in male infants.

  14. Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat.

    PubMed

    Johnson, Miranda D; Bouret, Sebastien G; Dunn-Meynell, Ambrose A; Boyle, Christina N; Lutz, Thomas A; Levin, Barry E

    2016-12-01

    Selectively bred diet-induced obese (DIO) rats become obese on a high-fat diet and are leptin resistant before becoming obese. Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (α-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY/AgRP neurons. Since amylin increases leptin signaling in adult rats, we treated DIO neonates with amylin during postnatal hypothalamic development and assessed leptin signaling, leptin-dependent ARC-PVN pathway development, and metabolic changes. DIO neonates treated with amylin from P0-6 and from P0-16 increased ARC leptin signaling and both AgRP and α-MSH ARC-PVN pathway development, but increased only POMC neuron number. Despite ARC-PVN pathway correction, P0-16 amylin-induced reductions in body weight did not persist beyond treatment cessation. Since amylin enhances adult DIO ARC signaling via an IL-6-dependent mechanism, we assessed ARC-PVN pathway competency in IL-6 knockout mice and found that the AgRP, but not the α-MSH, ARC-PVN pathway was reduced. These results suggest that both leptin and amylin are important neurotrophic factors for the postnatal development of the ARC-PVN pathway. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their α-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development.

  15. Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

    PubMed

    Brace, Lear E; Vose, Sarah C; Vargas, Dorathy F; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R

    2013-12-01

    Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction.

  16. Lifespan extension by dietary intervention in a mouse model of Cockayne Syndrome uncouples early postnatal development from segmental progeria

    PubMed Central

    Brace, Lear E.; Vose, Sarah C.; Vargas, Dorathy F.; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R.

    2014-01-01

    Cockayne Syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities and photosensitivity but without skin cancer predisposition. CS life expectancy ranges from 5 to 16 years for the two most severe forms (Types II and I, respectively). Mouse models of CS have thus far been of limited value due either to very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa-/- ∣ Xpa-/-). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction. PMID:23895664

  17. Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats.

    PubMed

    Strakovsky, Rita S; Lezmi, Stéphane; Flaws, Jodi A; Schantz, Susan L; Pan, Yuan-Xiang; Helferich, William G

    2014-03-01

    Genistein (Gen), the primary isoflavone in soy, has been shown to adversely affect various endocrine-mediated endpoints in rodents and humans. Soy formula intake by human infants has been associated with early age at menarche and decreased female-typical behavior in girls. Adipose deposition and expansion are also hormonally regulated and Gen has been shown to alter these processes. However, little is known about the impact of early-life soy intake on metabolic homeostasis in adulthood. The current study examined the impact of early-life Gen exposure on adulthood body composition (by magnetic resonance imaging) and the molecular signals mediating adipose expansion. From postnatal day (PND) 1 to 22, rat pups were daily orally dosed with 50mg/kg Gen to mimic blood Gen levels in human infants fed soy formula. Female but not male Gen-exposed rats had increased fat/lean mass ratio, fat mass, adipocyte size and number, and decreased muscle fiber perimeter. PND22 Gen-exposed females, but not males, had increased expression of adipogenic factors, including CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpβ), and peroxisome proliferator-activated receptor gamma (Pparγ). Furthermore, Wingless-related MMTV integration site 10b (Wnt10b), a critical regulator of adipogenic cell fate determination, was hypermethylated and had decreased expression in adipose of PND22 Gen-exposed females. These data suggest that developmental Gen exposure in rats has gender-specific effects on adiposity that closely parallel the effects of a postweaning high-fat diet and underscore the importance of considering timing of exposure and gender when establishing safety recommendations for early-life dietary Gen intake.

  18. Maternal screening for early postnatal vulnerability.

    PubMed

    Vivilaki, V G; Dafermos, V; Patelarou, Ev; Bick, D; Syngelaki, Ar; Tsopelas, N D; Bitsios, P; Petridou, E T; Vgontzas, Al N; Lionis, Chr

    2016-01-01

    Research has highlighted the wide impact of maternal mental health problems during and beyond the postpartum period and the public health role of community health professionals in early detection of women who may be at risk. This paper aims to describe, explore and test an a priori hypothesised conceptual model of postnatal experience, identifying the relationships between postnatal mental vulnerability and postnatal adjustment to maternal roles and attitudes, marital/partner-relationship and sense of coherence. Three validated self-report questionnaires (WAST, MAMA, SOC) measuring the variables of the encompassing framework and EPDS were administered in random order. The conceptual models were tested using the software IBM SPSS Statistics and LISREL and the tests performed were: Student's ttest, chi-square tests, Explanatory factor analysis using a Varimax rotation Principal Components Method, Confirmatory analysis -known as structural equation modelling- of principal components. Psychometric scores indicate high correlation between WAST, MAMA, SOC and EPDS. An exploratory factor analysis confirmed the role of SOC, specific MAMA subscales (maternal roles and attitudes, body image, sex, breasts, nausea) and WAST (relationship tension and emotional and physical abuse) subscales (KMO measure of sampling adequacy=0.735 and Bartlett's test of sphericity=184,786, df=36, p<0.0005). The latent variables confirmed with SEM were marital relationship, maternity experience and self-efficacy (Chi-square=28.45, df=24, P-value=0.24, RMSEA=0.046 p<0.05). Marital Relationship (Factor I: Eigenvalue=3.066) concerning lack of or disappointment with partner support, poor marital relationship and emotional/physical abuse has been associated with high levels of postpartum anxiety and depression. Maternity Experience (Factor II: Eigenvalue=1.280) representing postnatal roles and attitudes towards their infant can be as useful as mood changes for evaluation of mothers. Self

  19. Small particles disrupt postnatal airway development

    PubMed Central

    Lee, DongYoub; Wallis, Chris; Schelegle, Edward S.; Van Winkle, Laura S.; Plopper, Charles G.; Fanucchi, Michelle V.; Kumfer, Ben; Kennedy, Ian M.; Chan, Jackie K. W.

    2010-01-01

    Increasing numbers of epidemiologic studies associate air pollution exposure in children with decreased lung function development. The objective of this study was to examine the effects of exposure to combustion-generated fine [230 and 212 nm number mean aerodynamic particle diameter (NMAD)] to ultrafine (73 nm NMAD) particles differing in elemental (EC) and organic (OC) carbon content on postnatal airway development in rats. Neonatal Sprague-Dawley rats were exposed from postnatal day 7 through 25, and lung function and airway architecture were evaluated 81 days of age. In a separate group of rats, cell proliferation was examined after a single particle exposure at 7 days of age. Early life exposure to 73 nm high OC/EC particles altered distal airway architecture and resulted in subtle changes in lung mechanics. Early life exposure to 212 nm high OC/EC particles did not alter lung architecture but did alter lung mechanics in a manner suggestive of central airway changes. In contrast, early life exposure to 230 nm low OC/EC particles did not alter lung architecture or mechanics. A single 6-h exposure to 73 nm high OC/EC particle decreased airway cell proliferation, whereas 212 nm high OC/EC particles increased it and 230 nm low OC/EC particles did not. The early life exposure to ultrafine, high OC/EC particles results in persistent alterations in distal airway architecture that is characterized by an initial decrease in airway cell proliferation. PMID:20634362

  20. Histology Atlas of the Developing Mouse Hepatobiliary Hemolymphatic Vascular System with Emphasis on Embryonic Days 11.5-18.5 and Early Postnatal Development.

    PubMed

    Swartley, Olivia M; Foley, Julie F; Livingston, David P; Cullen, John M; Elmore, Susan A

    2016-07-01

    A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular development is dependent upon normal vasculogenesis, angiogenesis, and the transformation of vessels into their adult counterparts. Any alteration in vascular development has the potential to cause deformities or embryonic death. Numerous publications describe specific stages of vascular development relating to various organs, but a single resource detailing the stage-by-stage development of the vasculature pertaining to the hepatobiliary system has not been available. This comprehensive histology atlas provides hematoxylin & eosin and immunohistochemical-stained sections of the developing mouse blood and lymphatic vasculature with emphasis on the hepatobiliary system between embryonic days (E) 11.5-18.5 and the early postnatal period. Additionally, this atlas includes a 3-dimensional video representation of the E18.5 mouse venous vasculature. One of the most noteworthy findings of this atlas is the identification of the portal sinus within the mouse, which has been erroneously misinterpreted as the ductus venosus in previous publications. Although the primary purpose of this atlas is to identify normal hepatobiliary vascular development, potential embryonic abnormalities are also described. © The Author(s) 2016.

  1. The activation of cannabinoid receptors during early postnatal development reduces the expression of cell adhesion molecule L1 in the rat brain.

    PubMed

    Gómez, María; Hernández, Mariluz; Fernández-Ruiz, Javier

    2007-05-11

    Cannabinoid CB(1) receptors and their ligands emerge early in brain development and are abundantly expressed in certain brain regions that play key roles in processes related to cell proliferation and migration, neuritic elongation and guidance, and synaptogenesis. This would support the notion that the cannabinoid system might play a modulatory role in the regulation of these processes. We have recently presented preliminary in vivo evidence showing that this modulatory action might be exerted, among others, through regulating the levels of several key elements in these processes, such as the L1 protein. This was observed in various white matter areas of the rat forebrain. Because these preliminary in vivo experiments focused only in fetal ages, we concentrated now in the period of early postnatal development. To this end, we analyzed the effects of the cannabinoid agonist Delta(9)-tetrahydrocannabinol (Delta(9)-THC) daily administered since the 5th day of gestation on mRNA levels for L1 in different brain structures of rat neonates at different postnatal ages (PND1, PND5 and PND12). Our results revealed that Delta(9)-THC exposure affected the levels of L1 transcripts in specific brain structures only in PND1, these effects disappearing during further days. Thus, we found reduced L1-mRNA levels in grey matter regions, such as the cerebral cortex, septum nuclei, striatum, dentate gyrus and CA3 subfield of the Ammon horn. White matter areas and subventricular zones were, however, more resistant to Delta(9)-THC exposure at this postnatal age in contrast with the previous data obtained in the fetal brain. Importantly, the effects were influenced by gender of animals, since the reductions were always more marked in females than males, also in contrast with the data reported for the fetal brain. In summary, the cannabinoid system seems to modulate the levels of L1 in several brain structures during specific periods of development [late gestation (previous data) and very

  2. Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

    PubMed

    Richard, Caroline; Lewis, Erin D; Field, Catherine J

    2016-05-01

    Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

  3. Effects of Early Postnatal Alcohol Exposure on the Developing Retinogeniculate Projections in C57BL/6 Mice

    PubMed Central

    Dursun, İlknur; Jakubowska-Doğru, Ewa; Birsen, Elibol-Can; van der List, Deborah; Chapman, Barbara; Qi, Lihong; Berman, Robert F.

    2013-01-01

    Previous studies on the adverse effects of perinatal exposure to ethanol on the developing visual system mainly focused on retinal and optic nerve morphology. The aim of the present study was to investigate whether earlier reported retinal and optic nerve changes are accompanied by anomalies in eye-specific fiber segregation in the dorsal lateral geniculate nucleus (dLGN). C57BL/6 mice pups were exposed to ethanol by intragastric intubation at either 3 or 4 g/kg from postnatal days (PD) 3-10, the third trimester equivalent to human gestation. Control (C) and intubation control (IC) groups not exposed to ethanol were included. On PD9 retinogeniculate projections, were labeled by intraocular microinjections of cholera toxin-β (CTB) either conjugated to Alexa 488 (green) or 594 (red) administrated to the left and right eye, respectively. Pups were sacrificed 24 h after the last CTB injection. The results showed that ethanol exposure decreased the total number of dLGN neurons and significantly reduced the total dLGN projection as well as the contralateral and ipsilateral projection areas. PMID:23402901

  4. gamma-Aminobutyric acid (GABA): a fast excitatory transmitter which may regulate the development of hippocampal neurones in early postnatal life.

    PubMed

    Ben-Ari, Y; Tseeb, V; Raggozzino, D; Khazipov, R; Gaiarsa, J L

    1994-01-01

    The properties of neonatal GABAergic synapses were investigated in neurones of the hippocampal CA3 region. GABA, acting on GABAA receptors, provides most of the excitatory drive on immature CA3 pyramidal neurones at an early stage of development, whereas glutamatergic synapses (in particular, those mediated by AMPA receptors) are mostly quiescent. Thus, during the first postnatal week of life, bicuculline fully blocked spontaneous and evoked depolarising potentials, and GABAA receptor agonists depolarised CA3 pyramidal neurones. GABAA mediated currents also had a reduced sensitivity to benzodiazepines. In the presence of bicuculline, between P0 and P4, increasing the stimulus strength reveals an excitatory postsynaptic potential which is mostly mediated by NMDA receptors. During the same developmental period, pre- (but not post) synaptic GABAB inhibition is present. Intracellular injections of biocytin showed that the axonal network of the GABAergic interneurones is well developed at birth, whereas the pyramidal recurrent collaterals are only beginning to develop. Finally, chronic bicuculline treatment of hippocampal neurones in culture reduced the extent of neuritic arborisation, suggesting that GABA acts as a trophic factor in that period. In conclusion, it is suggested that during the first postnatal week of life, when excitatory inputs are still poorly developed, GABAA receptors provide the excitatory drive necessary for pyramidal cell outgrowth. Starting from the end of the first postnatal week of life, when excitatory inputs are well developed, GABA (acting on both GABAA and GABAB receptors) will hyperpolarise the CA3 pyramidal neurones and, as in the adult, will prevent excessive neuronal discharges. Our electrophysiological and morphological studies have shown that hippocampal GABAergic interneurones are in a unique position to modulate the development of CA3 pyramidal neurones. Developing neurones require a certain degree of membrane depolarisation, and a

  5. The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

    PubMed

    Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

    2016-01-01

    Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

  6. Methylxanthines during pregnancy and early postnatal life.

    PubMed

    Adén, Ulrika

    2011-01-01

    World-wide, many fetuses and infants are exposed to methylxanthines via maternal consumption of coffee and other beverages containing these substances. Methylxanthines (caffeine, theophylline and aminophylline) are also commonly used as a medication for apnea of prematurity.The metabolism of methylxanthines is impaired in pregnant women, fetuses and neonates, leading to accumulating levels thereof. Methylxanthines readily passes the placenta barrier and enters all tissues and thus may affect the fetus/newborn at any time during pregnancy or postnatal life, given that the effector systems are mature.At clinically relevant doses, the major effector system for methylxanthines is adenosine receptors. Animal studies suggest that adenosine receptors in the cardiovascular, respiratory and immune system are developed at birth, but that cerebral adenosine receptors are not fully functional. Furthermore animal studies have shown protective positive effects of methylxanthines in situations of hypoxia/ischemia in neonates. Similarly, a positive long-term effect on lung function and CNS development was found in human preterm infants treated with high doses of caffeine for apneas. There is now evidence that the overall benefits from methylxanthine therapy for apnea of prematurity outweigh potential short-term risks.On the other hand it is important to note that experimental studies have indicated that long-term effects of caffeine during pregnancy and postnatally may include altered behavior and altered respiratory control in the offspring, although there is currently no human data to support this.Some epidemiology studies have reported negative effects on pregnancy and perinatal outcomes related to maternal ingestion of high doses of caffeine, but the results are inconclusive. The evidence base for adverse effects of caffeine in first third of pregnancy are stronger than for later parts of pregnancy and there is currently insufficient evidence to advise women to restrict

  7. Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival.

    PubMed Central

    Li, H; Witte, D P; Branford, W W; Aronow, B J; Weinstein, M; Kaur, S; Wert, S; Singh, G; Schreiner, C M; Whitsett, J A

    1994-01-01

    We present an initial characterization of the murine Gsh-4 gene which is shown to encode a LIM-type homeodomain. Genes in this category are known to control late developmental cell-type specification events in simpler organisms. Whole mount and serial section in situ hybridizations show transient Gsh-4 expression in ventrolateral regions of the developing neural tube and hindbrain. Mice homozygous for a targeted mutation in Gsh-4 suffer early postnatal death resulting from immature lungs which do not inflate. Prenatal administration of progesterone and glucocorticoid, to extend gestational term and accelerate maturation, resulted in lung inflation at birth. Nevertheless, the hormonally treated mutants generally failed to survive beyond an hour after birth, due to ineffective breathing efforts. It is concluded that Gsh-4 plays a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung. Images PMID:7913017

  8. Growth trajectories in early childhood, their relationship with antenatal and postnatal factors, and development of obesity by age 9 years: results from an Australian birth cohort study.

    PubMed

    Giles, L C; Whitrow, M J; Davies, M J; Davies, C E; Rumbold, A R; Moore, V M

    2015-07-01

    In an era where around one in four children in the United Kingdom, the United States, and Australia are overweight or obese, the development of obesity in early life needs to be better understood. We aimed to identify groups of children with distinct trajectories of growth in infancy and early childhood, to examine any association between these trajectories and body size at age 9, and to assess the relative influence of antenatal and postnatal exposures on growth trajectories. Prospective Australian birth cohort study. In total, 557 children with serial height and weight measurements from birth to 9 years were included in the study. Latent class growth models were used to derive distinct groups of growth trajectories from birth to age 3½ years. Multivariable logistic regression models were used to explore antenatal and postnatal predictors of growth trajectory groups, and multivariable linear and logistic regression models were used to examine the relationships between growth trajectory groups and body size at age 9 years. We identified four discrete growth trajectories from birth to age 3½ years, characterised as low, intermediate, high, or accelerating growth. Relative to the intermediate growth group, the low group had reduced z-body mass index (BMI) (-0.75 s.d.; 95% confidence interval (CI) -1.02, -0.47), and the high and accelerating groups were associated with increased body size at age 9 years (high: z-BMI 0.70 s.d.; 95% CI 0.49, 0.62; accelerating: z-BMI 1.64 s.d.; 95% CI 1.16, 2.11). Of the antenatal and postnatal exposures considered, the most important differentiating factor was maternal obesity in early pregnancy, associated with a near quadrupling of risk of membership of the accelerating growth trajectory group compared with the intermediate growth group (odds ratio (OR) 3.72; 95% CI 1.15, 12.05). Efforts to prevent childhood obesity may need to be embedded within population-wide strategies that also pay attention to healthy weight for women in

  9. Early metabolic programming of puberty onset: impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system.

    PubMed

    Castellano, Juan M; Bentsen, Agnete H; Sánchez-Garrido, Miguel A; Ruiz-Pino, Francisco; Romero, Magdalena; Garcia-Galiano, David; Aguilar, Enrique; Pinilla, Leonor; Diéguez, Carlos; Mikkelsen, Jens D; Tena-Sempere, Manuel

    2011-09-01

    Kiss1 neurons have recently emerged as a putative conduit for the metabolic gating of reproduction, with leptin being a regulator of hypothalamic Kiss1 expression. Early perturbations of the nutritional status are known to predispose to different metabolic disorders later in life and to alter the timing of puberty; however, the potential underlying mechanisms remain poorly defined. Here we report how changes in the pattern of postnatal feeding affect the onset of puberty and evaluate key hormonal and neuropeptide [Kiss1/kisspeptin (Kp)] alterations linked to these early nutritional manipulations. Female rats were raised in litters of different sizes: small (four pups per dam: overfeeding), normal (12 pups per dam), and large litters (20 pups per litter: underfeeding). Postnatal overfeeding resulted in persistently increased body weight and earlier age of vaginal opening, as an external sign of puberty, together with higher levels of leptin and hypothalamic Kiss1 mRNA. Conversely, postnatal underfeeding caused a persistent reduction in body weight, lower ovarian and uterus weights, and delayed vaginal opening, changes that were paralleled by a decrease in leptin and Kiss1 mRNA levels. Kisspeptin-52 immunoreactivity (Kp-IR) in the hypothalamus displayed similar patterns, with lower numbers of Kp-IR neurons in the arcuate nucleus of postnatally underfed animals, and a trend for increased Kp-positive fibers in the periventricular area of early overfed rats. Yet, gonadotropin responses to Kp at puberty were similar in all groups, except for enhanced responsiveness to low doses of Kp-10 in postnatally underfed rats. In conclusion, our data document that the timing of puberty is sensitive to both overfeeding and subnutrition during early (postnatal) periods and suggest that alterations in hypothalamic expression of Kiss1/kisspeptin may underlie at least part of such programming phenomenon.

  10. Schizophrenia Risk Variation in the NRG1 gene Exerts Effects on NRG1-IV Splicing During Fetal and Early Postnatal Human Neocortical Development

    PubMed Central

    Paterson, Clare; Wang, Yanhong; Kleinman, Joel E.; Law, Amanda J.

    2015-01-01

    OBJECTIVE Neuregulin 1 (NRG1) is a multifunctional neurotrophin and a critical mediator of neurodevelopment and risk for schizophrenia. NRG1 undergoes extensive alternative splicing, and association of brain NRG1-IV isoform expression with the schizophrenia-risk polymorphism, rs6994992, is a potential molecular mechanism of risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique signaling capabilities, have been cloned in fetal brain. Because the developmental expression and genetic regulation of NRG1-IVNV in human brain and relationship to schizophrenia is unknown, the authors investigated the temporal dynamics of NRG1-IVNV transcription, compared to the major NRG1 isoforms (types I-IV), across human prenatal and postnatal prefrontal cortical development and examined the association of rs6994992 with NRG1-IVNV expression. METHOD NRG1, types I-IV and NRG1-IVNV isoform expression was evaluated using quantitative real-time PCR in prefrontal cortex during human fetal brain development (14-39 weeks gestation: N=41) and postnatally through aging (age range 0-83 years: N=195). The association of rs6994992 genotype with NRG1-IVNV expression was determined. In-vitro assays were performed to determine the subcellular distribution and proteolytic processing of NRG1-IVNV isoforms. RESULTS Expression of NRG1, types I, II, III was temporally regulated during human prenatal and postnatal neocortical development and the trajectory of NRG1-IVNV was unique, being expressed from 16 weeks gestation until 3 years of age, after which it was undetectable. NRG1-IVNVs expression was associated with rs6994992 genotype, whereby homozygosity for the schizophrenia-risk allele (T) conferred lower cortical NRG1-IVNV levels. Finally, in-vitro cellular assays demonstrate that NRG1-IVNV is a novel nuclear enriched, truncated NRG1 protein that is resistant to proteolytic processing. CONCLUSION This study provides the first quantitative map of NRG1 isoform expression during human

  11. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants.

    PubMed

    Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A; Löfqvist, Chatarina; Smith, Lois E H; Hård, Anna-Lena

    2016-09-01

    The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.

  12. LPA receptor activity is basal specific and coincident with early pregnancy and involution during mammary gland postnatal development

    PubMed Central

    Acosta, Deanna; Bagchi, Susmita; Broin, Pilib Ó; Hollern, Daniel; Racedo, Silvia E.; Morrow, Bernice; Sellers, Rani S.; Greally, John M.; Golden, Aaron; Andrechek, Eran; Wood, Teresa; Montagna, Cristina

    2016-01-01

    During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages. Using RNA-seq, we show that basal cells are extraordinarily transcriptionally dynamic throughout pregnancy when compared to luminal cells. We identified gene expression changes that define specific basal functions acquired during development that led to the identification of novel markers. Enrichment analysis of gene sets from 24 mouse models for breast cancer pinpoint to a potential new function for insulin-like growth factor 1 (Igf1r) in the basal epithelium during lactogenesis. We establish that β-catenin signaling is activated in basal cells during early pregnancy, and demonstrate that this activity is mediated by lysophosphatidic acid receptor 3 (Lpar3). These findings identify novel pathways active during functional maturation of the adult mammary gland. PMID:27808166

  13. The Postnatal Development of Spinal Sensory Processing

    NASA Astrophysics Data System (ADS)

    Fitzgerald, Maria; Jennings, Ernest

    1999-07-01

    The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.

  14. Ozone exposure during the early postnatal period alters the timing and pattern of alveolar growth and development in nonhuman primates.

    PubMed

    Avdalovic, Mark V; Tyler, Nancy K; Putney, Lei; Nishio, Susie J; Quesenberry, Sherri; Singh, Parmjit J; Miller, Lisa A; Schelegle, Edward S; Plopper, Charles G; Vu, Thiennu; Hyde, Dallas M

    2012-10-01

    Exposure to oxidant air pollutants in early childhood, with ozone as the key oxidant, has been linked to significant decrements in pulmonary function in young adults and exacerbation of airway remodeling in asthma. Development of lung parenchyma in rhesus monkeys is rapid during the first 2 years of life (comparable to the first 6 years in humans). Our hypothesis is that ozone inhalation during infancy alters alveolar morphogenesis. We exposed infant rhesus monkeys biweekly to 5, 8 hr/day, cycles of 0.5 ppm ozone with or without house dust mite allergen from 1 to 3 or 1 to 6 months of age. Monkeys were necropsied at 3 and 6 months of age. A morphometric approach was used to quantify changes in alveolar volume and number, the distribution of alveolar size, and capillary surface density per alveolar septa. Quantitative real time PCR was used to measure the relative difference in gene expression over time. Monkeys exposed to ozone alone or ozone combined with allergen had statistically larger alveoli that were less in number at 3 months of age. Alveolar capillary surface density was also decreased in the ozone exposed groups at 3 months of age. At 6 months of age, the alveolar number was similar between treatment groups and was associated with a significant rise in alveolar number from 3 to 6 months of age in the ozone exposed groups. This increase in alveolar number was not associated with any significant increase in microvascular growth as measured by morphometry or changes in angiogenic gene expression. Inhalation of ozone during infancy alters the appearance and timing of alveolar growth and maturation. Understanding the mechanism involved with this altered alveolar growth may provide insight into the parenchymal injury and repair process that is involved with chronic lung diseases such as severe asthma and COPD. Copyright © 2012 Wiley Periodicals, Inc.

  15. The Prodrome of Autism: Early Behavioral and Biological Signs, Regression, Peri- and Post-Natal Development and Genetics

    ERIC Educational Resources Information Center

    Yirmiya, Nurit; Charman, Tony

    2010-01-01

    Autism is one of the most heritable neurodevelopmental conditions and has an early onset, with symptoms being required to be present in the first 3 years of life in order to meet criteria for the "core" disorder in the classification systems. As such, the focus on identifying a prodrome over the past 20 years has been on pre-clinical…

  16. The Prodrome of Autism: Early Behavioral and Biological Signs, Regression, Peri- and Post-Natal Development and Genetics

    ERIC Educational Resources Information Center

    Yirmiya, Nurit; Charman, Tony

    2010-01-01

    Autism is one of the most heritable neurodevelopmental conditions and has an early onset, with symptoms being required to be present in the first 3 years of life in order to meet criteria for the "core" disorder in the classification systems. As such, the focus on identifying a prodrome over the past 20 years has been on pre-clinical…

  17. Radiology of postnatal skeletal development. Pt. 7

    SciTech Connect

    Ogden, J.A.; Phillips, S.B.

    1983-02-01

    Twenty-four pairs of scapulae from fetal specimens and 35 pairs of scapulae from postnatal cadavers ranging in age from full-term neonates to 14 years, were studied morphologically and roentgenographically. Air-cartilage interfacing was used to demonstrate both the osseous and cartilaginous contours. When the entire chondro-osseous dimensions, rather than just the osseous dimensions, were measured, the scapula had a height-width ratio ranging from 1.36 to 1.52 (average 1.44) during most of fetal development. The exceptions were three stillborns with camptomelic, thanatophoric, and achondrogenic dwarfism in which the ratio averaged 0.6. At no time during fetal development was the glenoid cavity convex; it always had a concave articular surface. However, the osseous subchrondral countour was often flat or slightly convex. In the postnatal period the height-width ratio averaged 1.49. The ratio remained virtually unchanged throughout skeletal growth and maturation. In a patient with unilateral Sprengel's deformity the ratio for the normal side was 1.5, while the abnormal was 1.0. The cartilaginous glenoid cavity was always concave during postnatal development, even in the specimens with major structural deformities, although the subchondral osseous contour was usually flat or convex during the first few years of postnatal development. Ossification of the coracoid process began with the development of a primary center at three to four months. A bipolar physis was present between the primary coracoid center and the primary scapular center until late adolescence.

  18. Intestinal absorption and renal reabsorption of calcium throughout postnatal development

    PubMed Central

    Beggs, Megan R

    2017-01-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  19. Intestinal absorption and renal reabsorption of calcium throughout postnatal development.

    PubMed

    Beggs, Megan R; Alexander, R Todd

    2017-04-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  20. [The administration of interleukin-1beta during early postnatal develop ment impairs FGF2, but not TIMP1, mRNA expression in brain structures of adult rats].

    PubMed

    Trofimov, A N; Zubareva, O E; Shvarts, A P; Ishchenko, A M; Klimenko, V M

    2014-09-01

    According to the Neurodevelopmental hypothesis, the long-lasting cognitive deficit in schizophrenia and other types of neuropathology may occur by injurious factors, such as hypoxia, traumas, infections that take place during pre- and postnatal development, at least at early stages. These pathological conditions are often associated with the high production of pro-inflammatory cytokine interleukin-1B (IL-1B) by the cells of immune and nervous systems. We investigated the expression of genes involved in the neuroplastic regulation (Fgf2 and Timp2) in medial prefrontal cortex and dorsal and ventral regions of hippocampus of adult rats that were treated with IL-1beta between P15 and P21. The learning impairment in IL-1beta-treated rats is accompanied by lower FGF-2 mRNA levels in medial prefrontal cortex and ventral (not dorsal) hippocampus, but TIMP-1 was not affected. No differences in TIMP-1 and FGF-2 mRNA expressions were observed in untrained IL-1beta-treated when compared to control rats.

  1. Gestational and Early Postnatal Exposure to Simulated High Altitude Does Not Modify Postnatal Body Mass Growth Trajectory in the Rat

    PubMed Central

    Champin, Graciela M.; Bozzini, Clarisa; Alippi, Rosa M.

    2014-01-01

    Abstract Bozzini, Carlos E, Graciela M. Champin, Clarisa Bozzini, and Rosa M. Alippi. Gestational and Early Postnatal Exposure to Simulated High Altitude Does Not Modify Postnatal Body Mass Growth Trajectory in the Rat. High Alt Med Biol 15:418–421, 2014.—Postnatal hypoxia blunts body mass growth. It is also known that the quality of the fetal environment can influence the subsequent adult phenotype. The main purpose of the study was to determine whether gestational hypoxia and early postnatal hypoxia are able to blunt growth when the offspring is raised under normoxia. Hypobaric hypoxia was induced in simulated high altitude (SHA) chambers in which air was maintained at 380 mmHg (5450 m). Mature Sprague-Dawley rats of both sexes were divided in normoxic (NX) and hypoxic (HX) groups and, in the case of the HX group, maintained for 1 month at 5450 m. Mating was then allowed under NX or HX conditions. Offspring were NX-NX, NX-HX, HX-HX, or HX-NX: the first term indicates NX or HX during both gestation and the first 30 days of life; the second term indicates NX or HX during postnatal life between days 30 and 133. Body mass (g) was measured periodically and body mass growth rate (BMGR, g/d) was estimated between days 33 and 65 of postnatal life. Results can be summarized as follows: 1) BM was significantly higher in NX than in HX rats at weaning; 2) BMGR was not significantly different between NX-NX and HX-NX rats, and between HX-HX and NX-HX animals; and 3) BMGR was significantly higher in rats living under NX conditions than in those living under HX conditions during postnatal life. Data suggest that that hypobaric hypoxia during gestational and early postnatal development of rats does not alter the regulation of body mass growth in rats when compared to that seen under sea-level conditions. PMID:25184739

  2. Early post-natal development of the mandibular permanent first molar in infants with unilateral complete cleft lip and palate.

    PubMed

    Hermann, N V; Darvann, T A; Kreiborg, S

    2017-09-05

    Studies have shown that the mandibular permanent first molar (M1inf ) in young children with isolated cleft palate is characterized by delay in maturation and has reduced crown width. Consequently, it is of interest to investigate the early maturation and width of the follicle and crown of M1inf in children with combined cleft lip and palate. Retrospective, longitudinal study. Cephalometric X-rays of 47 consecutive Danish children with UCCLP (37 males; 10 females) and 44 with unilateral incomplete cleft lip (UICL) (29 males; 15 females) examined at 2 and 22 months of age. UICL served as control group. Maturation (according to Haavikko), width of follicle (FW) and crown (CW) of M1inf were assessed. The maturation of the first mandibular molar was delayed in both genders at 2 and 22 months of age. FW and CW were smaller in children with UCCLP at both 2 and 22 months of age. There was a positive correlation between maturation and FW. Maturation of the first mandibular molar is delayed in both genders, and FW and CW were reduced in UCCLP compared to controls. Maturation was correlated with FW. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. In vivo two-photon imaging measuring the blood-brain barrier permeability during early postnatal brain development in rodent

    NASA Astrophysics Data System (ADS)

    Shi, Lingyan; Rodríguez-Contreras, Adrián.

    2016-03-01

    The blood-brain barrier (BBB) is a unique structure between the cerebral blood circulation and the delicate neural environment that is important in regulating the movement of molecules and ions involved in brain development and function. However, little is known about the physiological permeability of molecules and ions across the BBB during brain development. In this study we applied an innovative approach to examine the development of BBB properties quantitatively. Two-photon microscopy was employed to measure BBB permeability in real time in vivo. Vascular growth and specific interactions between astrocyte end feet and microvessels were studied by using a combination of IB4 histochemistry, immunohistochemistry, confocal microscopy and 3D analysis.

  4. The UNC-Wisconsin Rhesus Macaque Neurodevelopment Database: A Structural MRI and DTI Database of Early Postnatal Development

    PubMed Central

    Young, Jeffrey T.; Shi, Yundi; Niethammer, Marc; Grauer, Michael; Coe, Christopher L.; Lubach, Gabriele R.; Davis, Bradley; Budin, Francois; Knickmeyer, Rebecca C.; Alexander, Andrew L.; Styner, Martin A.

    2017-01-01

    Rhesus macaques are commonly used as a translational animal model in neuroimaging and neurodevelopmental research. In this report, we present longitudinal data from both structural and diffusion MRI images generated on a cohort of 34 typically developing monkeys from 2 weeks to 36 months of age. All images have been manually skull stripped and are being made freely available via an online repository for use by the research community. PMID:28210206

  5. Suppression of active sleep by chronic treatment with chlorimipramine during early postnatal development: effects upon adult sleep and behavior in the rat.

    PubMed

    Mirmiran, M; van de Poll, N E; Corner, M A; van Oyen, H G; Bour, H L

    1981-01-05

    In an attempt to study the possible role of active sleep in brain development, male rats were injected twice daily with chlorimipramine, a potent monoamine reuptake blocker, from 1 week to 3 weeks of postnatal age. AS was reduced to less than 10% of total sleep time, the level found in mature rats. Most of the AS reduction was compensated for by quiet sleep but a slight increase in wakefulness also occurred, owing to brief interruptions of sleep at times when AS was expected. In adulthood, the AS-deprived rats showed a higher percentage of AS than did the controls, due to an increase in frequency and duration of AS epochs. Moreover, many of the epochs contained abnormally frequent and strong jerky body movements and rapid-eye-movements, reminiscent of neonatal AS patterns. In addition, the amplitude of hippocampal theta waves during AS was greater than in control rats. The chlorimipramine-treated rats also showed behavioral abnormalities in later life. On the open field test exploratory behavior was much reduced, while increased rearing and defecation occurred. Masculine sexual performance was severely deficient, primarily due to the low level of intromissions and ejaculations. Experimental animals performed less efficiently than controls on a temporal learning task (differential reinforcement of low response rate) and responded more rapidly on a spatial task (left-right alternation learning). These results demonstrate that early interference with the functioning of monoaminergic systems can have long-lasting physiological and behavioral consequences. Furthermore, they are consistent with the hypothesis that AS is an important factor in normal brain development.

  6. Postnatal development of the kidney juxtaglomerular apparatus in rats.

    PubMed

    Vesna, L; Spomenka, M

    1980-01-01

    The development of the juxtaglomerular (JG) apparatus in the rat kidney was investigated at different times of postnatal life (1, 2, 3, 5, 7, 10, 15, 30 and 60 days). On the 1st day after birth, secretory granules were found in JG cells in preglomerular arterioles of juxtamedular nephrons and in interglobular arteries. JG indices are high at this stage and decrease until the 5th day, then gradually rise until the 60th day. The possible reasons for such findings are discussed. Macula densa cells start to differ as early as the 1st day after birth. They are very distinct already at 2 days and they reach typical organization by the 15th day. Extraglomerular mesangial cells are few in early postnatal life. Their number increases later on. The parallelism between nephrogenesis and development is discussed.

  7. Protein Expression Dynamics During Postnatal Mouse Brain Development

    PubMed Central

    Laeremans, Annelies; Van de Plas, Babs; Clerens, Stefan; Van den Bergh, Gert; Arckens, Lutgarde; Hu, Tjing-Tjing

    2013-01-01

    We explored differential protein expression profiles in the mouse forebrain at different stages of postnatal development, including 10-day (P10), 30-day (P30), and adult (Ad) mice, by large-scale screening of proteome maps using two-dimensional difference gel electrophoresis. Mass spectrometry analysis resulted in the identification of 251 differentially expressed proteins. Most molecular changes were observed between P10 compared to both P30 and Ad. Computational ingenuity pathway analysis (IPA) confirmed these proteins as crucial molecules in the biological function of nervous system development. Moreover, IPA revealed Semaphorin signaling in neurons and the protein ubiquitination pathway as essential canonical pathways in the mouse forebrain during postnatal development. For these main biological pathways, the transcriptional regulation of the age-dependent expression of selected proteins was validated by means of in situ hybridization. In conclusion, we suggest that proteolysis and neurite outgrowth guidance are key biological processes, particularly during early brain maturation. PMID:25157209

  8. Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity.

    PubMed

    Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun; Thamotharan, Shanthie; Shin, Bo-Chul; Stout, David; Devaskar, Sherin U

    2012-06-01

    Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation-induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype.

  9. Postnatal testicular development in the Chinchilla rabbit.

    PubMed

    Vigueras-Villaseñor, Rosa María; Montelongo-Solís, Paola; Chávez-Saldaña, Margarita Dolores; Gutiérrez-Pérez, Oscar; Arteaga-Silva, Marcela; Rojas-Castañeda, Julio César

    2013-09-01

    The Chinchilla rabbit is a breed with high commercial value and nowadays is increasingly used in various fields of biomedical research, however, its postnatal reproductive biology has been little studied. The aim of the present study was to investigate the postnatal development of the testis in this rabbit breed to determine both the proliferative periods and apoptosis. 30 rabbits aged 3-100 days old were used in the study. Determination of the period of differentiation of gonocytes to spermatogonia (50dpp), the periods of proliferation and apoptosis of their cells, as well as the beginning of spermatogenesis (60dpp) and the different stages of the seminiferous epithelium cycle were made. We found that these testicular developments were closer to that of humans when compared with rats, a species commonly employed in reproductive research. On comparing these results with those obtained from other breeds, there are clear differences favoring the use of this species as a research model in the field of male reproductive biology. Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. Postnatal Growth and Psychomotor Development in Small for Gestational Age Brazilian Infants.

    ERIC Educational Resources Information Center

    Paine, Patricia Ann; Pasquali, Luiz

    1984-01-01

    The early psychomotor development (DQ) of 29 term small-for-gestational-age Brazilian infants was shown to be more dependent on postnatal growth than the DQ of 51 term appropriate-for-gestational-age infants. (Author/RH)

  11. Early Postnatal Blood Manganese Levels and Children’s Neurodevelopment

    PubMed Central

    Henn, Birgit Claus; Ettinger, Adrienne S.; Schwartz, Joel; Téllez-Rojo, Martha María; Lamadrid-Figueroa, Héctor; Hernández-Avila, Mauricio; Schnaas, Lourdes; Amarasiriwardena, Chitra; Bellinger, David C.; Hu, Howard; Wright, Robert O.

    2011-01-01

    Background Recent evidence suggests that low-level environmental exposure to manganese adversely affects child growth and neurodevelopment. Previous studies have addressed the effects of prenatal exposure, but little is known about developmental effects of early postnatal exposure. Methods We studied 448 children born in Mexico City from 1997 through 2000, using a longitudinal study to investigate neurotoxic effects of early life manganese exposure. Archived blood samples, collected from children at 12 and 24 months of age, were analyzed for manganese levels using inductively-coupled plasma mass spectrometry. Mental and psychomotor development were scored using Bayley Scales of Infant Development at 6-month intervals between 12 and 36 months of age. Results At 12 months of age, the mean (SD) blood manganese level was 24.3 (4.5) μg/l and the median was 23.7 μg/l; at 24 months, these values were 21.1 (6.2) μg/l and 20.3 μg/l, respectively. Twelve- and 24-month manganese concentrations were correlated (Spearman correlation = 0.55) and levels declined over time (β = −5.7 [95% CI = −6.2 to −5.1]). We observed an inverted U-shaped association between 12-month blood manganese and concurrent mental development scores (compared with the middle 3 manganese quintiles, for the lowest manganese quintile, β = −3.3 [−6.0 to −0.7] and for the highest manganese quintile, β = −2.8 [−5.5 to −0.2]). This 12-month manganese effect was apparent but diminished with mental development scores at later ages. The 24-month manganese levels were not associated with neurodevelopment. Conclusions These results suggest a possible biphasic dose-response relationship between early-life manganese exposure at lower exposure levels and infant neurodevelopment. The data are consistent with manganese as both an essential nutrient and a toxicant. PMID:20549838

  12. Quantitative Proteomic Analysis of Rat Condylar Chondrocytes during Postnatal Development.

    PubMed

    Jiang, Li Ting; Xie, Yin Yin; Wei, Li; Zhou, Qi; Shen, Xing; Gao, Yi Ming; Jiang, Xin Quan

    To investigate differentially expressed proteins in rat mandibular condylar cartilage (MCC) chondrocytes caused by initial mastication for short postnatal periods. Four groups of protein samples were extracted from primary cultured rat MCC chondrocytes, harvested from eigthy postnatal SD rats aged 1,7,14 and 28 days, with twenty in each group. Total proteins were labelled with isobaric tags for relative and absolute quantification (iTRAQ) reagents. Two-dimensional nano-high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization-time-of-flight/ time-of-flight (MALDI-TOF/TOF) mass spectrometry analysis with iTRAQ technique were performed. All data were analysed by MASCOT software with the SWISSPROT protein database. Furthermore, bioinformatics and statistical analysis were performed to classify their cellular components, biological processes, molecular functions and metabolic pathway by the PANTHER database. In total, 137 differentially expressed proteins were identified during MCC growth and were assigned to one or more cellular components. According to the PANTHER analysis, a significant proportion of proteins are involved in the metabolic process, cellular process, biological regulation, developmental process and response to stimulus. The most extensive molecular function was 43% in catalytic activity. In addition, it was found that proteins in MCC chondrocytes change markedly on the growth stage of eruption of the teeth. This study provides an integrated perspective of molecular mechanisms regulating early normal postnatal growth and development of rat MCC at the protein level.

  13. MEAL PARAMETERS AND VAGAL GASTROINTESTINAL AFFERENTS IN MICE THAT EXPERIENCED EARLY POSTNATAL OVERNUTRITION

    PubMed Central

    Biddinger, Jessica E.; Fox, Edward A.

    2010-01-01

    Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component - the vagus nerve - has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal-size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 hour/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. PMID:20403369

  14. Early postnatal stress suppresses the developmental trajectory of hippocampal pyramidal neurons: the role of CRHR1.

    PubMed

    Liu, Rui; Yang, Xiao-Dun; Liao, Xue-Mei; Xie, Xiao-Meng; Su, Yun-Ai; Li, Ji-Tao; Wang, Xiao-Dong; Si, Tian-Mei

    2016-12-01

    Adverse experiences early in life hamper the development and maturation of the hippocampus, but how early-life stress perturbs the developmental trajectory of the hippocampus across various life stages and the underlying molecular mechanisms remain to be investigated. In this study, we stressed male mice from postnatal day 2 (P2) to P9, and examined the potential role of CRHR1 in postnatal stress-induced structural remodeling of hippocampal CA3 pyramidal neurons directly after stress (P9), in mid-adolescence (P35) and in adulthood (P90). We found that early-life stress exposure significantly reduced apical dendritic arborization and spine density in CA3 neurons on P9 and P90. Moreover, postnatally stressed neurons underwent increased pruning of spines, especially thin spines, between P35 and P90. These stress-induced immediate and long-term structural abnormalities could be abolished by daily systemic administration of the CRHR1 antagonist antalarmin (20 µg/g of body weight) during stress exposure. However, such treatment strategy failed to attenuate the deleterious stress effects in mid-adolescence on P35. We then extended antalarmin treatment until the end of the second postnatal week, and found that prolonged blockade of CRHR1 could prevent the mid-term impact of early postnatal stress on structural remodeling of CA3 neurons. Our study characterized the influences of early-life stress on the developmental trajectory of hippocampal pyramidal neurons, and highlighted the critical role of CRHR1 in modulating these negative outcomes evoked by early-life stress.

  15. Enhancing fathers' educational experiences during the early postnatal period.

    PubMed

    McKellar, Lois; Pincombe, Jan; Henderson, Ann

    2008-01-01

    Since the 1970s, men have been encouraged to actively participate in the childbirth process, resulting in a shared experience for couples. Nevertheless, after the baby is born, many fathers find themselves displaced, unsure of how to embrace the transition to parenthood. The shift in cultural practice and evolving needs of families calls for the recognition of fathers as well as mothers in the provision of midwifery services. Innovative strategies must be considered to enhance postnatal education that is father-inclusive and responsive to the needs of families in the 21st century. This article introduces one strategy created from an action research study conducted to develop, implement, and evaluate strategies to improve postnatal education for parents.

  16. Postnatal development of the human sternum.

    PubMed

    O'Neal, M L; Dwornik, J J; Ganey, T M; Ogden, J A

    1998-01-01

    Postnatal development and maturation of the human sternum are highly variable. Endochondral ossification centers (sternebrae) form within each cartilaginous segment of the sternum, with each center enveloped by a spherical growth plate. Within a cartilaginous center there may be either one or two ossification centers, those with two centers retaining and reflecting features of their bilateral embryonic origin. Malaligned bifid centers are clearly associated with rib articulation asymmetry as well. Expansion of individual ossification centers progresses within the peripheral cartilaginous domains of the sternum. With respect to the rostrocaudal axis, sternebrae form between the costosternal articulations. Consistent with the biology of endochondral transition, cartilage canals are evident throughout unossified regions of the hyaline matrix. Expanding ossification of adjacent sternebrae results in depletion of the common area of cartilage between the two sternebrae, and eventually in physiologic epiphysiodesis. Fusion of the mesosternebrae reciprocates the initial pattern of sternebral ossification site appearance, proceeding in a caudal-to-cranial direction. Union of adjacent sternebrae, initiated through a central osseous bridge, progresses through anterior, lateral, cephalocaudal, and posterior domains to achieve synostosis. Accessory and bifid centers of ossification within the same intercostal space coalesce prior to adjoining adjacent sternebrae. Manubriosternal fusion is rare due to the presence of a fibrocartilaginous joint restricting ossification. The xiphoid process remains connected to the most caudal mesosternum via a common zone of hyaline cartilage that ossifies by middle to late adulthood. A single pattern of development does not appear fundamental to successful growth of the sternum, as morphological variants were common.

  17. Subtle alterations in breathing and heart rate control in the 5-HT1A receptor knockout mouse in early postnatal development.

    PubMed

    Barrett, Karlene T; Kinney, Hannah C; Li, Aihua; Daubenspeck, J Andrew; Leiter, James C; Nattie, Eugene E

    2012-11-01

    We hypothesized that absence of the 5-HT(1A) receptor would negatively affect the development of cardiorespiratory control. In conscious wild type (WT) and 5-HT(1A) receptor knockout (KO) mice, we measured resting ventilation (Ve), oxygen consumption (Vo(2)), heart rate (HR), breathing and HR variability, and the hypercapnic ventilatory response (HCVR) at postnatal day 5 (P5), day 15 (P15), and day 25 (P25). In KO mice compared with WT, we found a 17% decrease in body weight at only P5 (P < 0.01) and no effect on Vo(2). Ve was significantly (P < 0.001) lower at P5 and P25, but there was no effect on the HCVR. Breathing variability (interbreath interval), measured by standard deviation, the root mean square of the standard deviation (RMSSD), and the product of the major (L) and minor axes (T) of the Poincaré first return plot, was 57% to 187% higher only at P5 (P < 0.001). HR was 6-10% slower at P5 (P < 0.001) but 7-9% faster at P25 (P < 0.001). This correlated with changes in the spectral analysis of HR variability; the low frequency to high frequency ratio was 47% lower at P5 but 68% greater at P25. The RMSSD and (L × T) of HR variability were ~2-fold greater at P5 only (P < 0.001; P < 0.05). We conclude that 5-HT(1A) KO mice have a critical period of potential vulnerability at P5 when pups hypoventilate and have a slower respiratory frequency and HR with enhanced variability of both, suggesting abnormal maturation of cardiorespiratory control.

  18. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

    PubMed

    Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

    2015-03-01

    The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development.

  19. How postnatal insults may program development: studies in animal models.

    PubMed

    Dalmaz, Carla; Noschang, Cristie; Krolow, Rachel; Raineki, Charlis; Lucion, Aldo B

    2015-01-01

    During the postnatal period, the nervous system is modified and shaped by experience, in order to adjust it to the particular environment in which the animal will live. This plasticity, one of the most remarkable characteristics of the nervous system, promotes adaptive changes, but it also makes brain more vulnerable to insults. This chapter will focus on the effects of interventions during the postnatal development in animal models of neonatal handling (usually up to 15 min of handling) and maternal separation (usually at least for 3 h). Sex-specific changes and effects of prepubertal stress such as social isolation later on in life were also considered. These interventions during development induce long-lasting traces in the pups' nervous system, which will be reflected in changes in neuroendocrine functions, including the hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axes; anxiety and cognitive performance; and feeding, sexual, and social behavior. These enduring changes may be adaptive or maladaptive, depending on the environment in which the animal will live. The challenge researchers facing now is to determine how to reverse the deleterious effects that may result from early-life stress exposure.

  20. Histology atlas of the developing mouse hepatobiliary hemolymphatic vascular system with emphasis on embryonic days 11.5-18.5 and early postnatal development

    USDA-ARS?s Scientific Manuscript database

    A critical event in fetal development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has lead pathologists and scientists to utilize transgenic mice to identify developmental disorders associated with the hepatobiliary vascular system. Va...

  1. Properties of synaptic transmission from the reticular formation dorsal to the facial nucleus to trigeminal motoneurons during early postnatal development in rats.

    PubMed

    Gemba-Nishimura, A; Inoue, T; Nakamura, S; Nakayama, K; Mochizuki, A; Shintani, S; Yoshimura, S

    2010-03-31

    We previously reported that electrical stimulation of the reticular formation dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at short latencies and that RdVII neurons were antidromically activated by stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory premotor neurons targeting the MoV are likely located in the RdVII. We thus examined the properties of synaptic transmission from the RdVII to jaw-closing and jaw-opening motoneurons in horizontal brainstem preparations from developing rats using voltage-sensitive dye, patch-clamp recordings and laser photostimulation. Electrical stimulation of the RdVII evoked optical responses in the MoV. Combined bath application of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV) reduced these optical responses, and addition of the glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline further reduced the remaining responses. Electrical stimulation of the RdVII evoked postsynaptic currents (PSCs) in all 19 masseter motoneurons tested in postnatal day (P)1-4 rats, and application of CNQX and the NMDA receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced the PSC amplitudes by more than 50%. In the presence of CNQX and CPP, the GABA(A) receptor antagonist SR95531 further reduced PSC amplitude, and addition of strychnine abolished the remaining PSCs. Photostimulation of the RdVII with caged glutamate also evoked PSCs in masseter motoneurons of P3-4 rats. In P8-11 rats, electrical stimulation of the RdVII also evoked PSCs in all 14 masseter motoneurons tested, and the effects of the antagonists on the PSCs were similar to those in P1-4 rats. On the other hand, RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested. These results suggest that both neonatal and

  2. Early Postnatal B Cell Ontogeny and Antibody Repertoire Maturation in the Opossum, Monodelphis domestica

    PubMed Central

    Wang, Xinxin; Sharp, Alana R.; Miller, Robert D.

    2012-01-01

    Marsupials are a lineage of mammals noted for giving birth to highly altricial young, which complete much of their “fetal” development externally attached to a teat. Postnatal B cell ontogeny and diversity was investigated in a model marsupial species, the gray short-tailed opossum, Monodelphis domestica. The results support the initiation of B cell development late in gestation and progressing into the first two weeks of postnatal life. Transcription of CD79a and CD79b was detected in embryonic tissue prior to birth, while immunoglobulin heavy chain locus transcription was not detected until the first postnatal 24 hours. Transcription of the Ig light chains was not detected until postnatal day 7 at the earliest. The predicted timing of the earliest appearance of mature B cells and completion of gene rearrangements is consistent with previous analyses on the timing of endogenous antibody responses in newborn marsupials. The diversity of early B cell IgH chains is limited, as has been seen in fetal humans and mice, but lacks bias in the gene segments used to encode the variable domains. Newborn light chain diversity is, from the start, comparable to that of the adult, consistent with an earlier hypothesis that light chains contribute extensively to antibody diversity in this species. PMID:23029324

  3. Early postnatal B cell ontogeny and antibody repertoire maturation in the opossum, Monodelphis domestica.

    PubMed

    Wang, Xinxin; Sharp, Alana R; Miller, Robert D

    2012-01-01

    Marsupials are a lineage of mammals noted for giving birth to highly altricial young, which complete much of their "fetal" development externally attached to a teat. Postnatal B cell ontogeny and diversity was investigated in a model marsupial species, the gray short-tailed opossum, Monodelphis domestica. The results support the initiation of B cell development late in gestation and progressing into the first two weeks of postnatal life. Transcription of CD79a and CD79b was detected in embryonic tissue prior to birth, while immunoglobulin heavy chain locus transcription was not detected until the first postnatal 24 hours. Transcription of the Ig light chains was not detected until postnatal day 7 at the earliest. The predicted timing of the earliest appearance of mature B cells and completion of gene rearrangements is consistent with previous analyses on the timing of endogenous antibody responses in newborn marsupials. The diversity of early B cell IgH chains is limited, as has been seen in fetal humans and mice, but lacks bias in the gene segments used to encode the variable domains. Newborn light chain diversity is, from the start, comparable to that of the adult, consistent with an earlier hypothesis that light chains contribute extensively to antibody diversity in this species.

  4. Development of mucociliary transport in the postnatal ferret trachea.

    PubMed

    Voter, K Z; Leigh, M W; Boat, T F; Carson, J L; Wood, R E

    1992-10-01

    Little is known of the developmental aspects of mucociliary transport. Previous studies have documented that newborn ferret trachea has very few ciliated cells but numerous immature secretory cells in the epithelium and only rudimentary submucosal glands. Rapid and complete maturation occurs in the first postnatal month. This study examines mucociliary transport during this period of rapid maturation. We made direct observations of particle movement across the epithelium of ferret tracheas. No mucus transport could be demonstrated on the first day of life. Transport was discernible, although sporadic and slow, by 7 days and reached adult levels (10.7 +/- 3.7 mm/min) by 28 postnatal days. The emergence of transport capability correlated well with previously described developmental changes in ciliation, mucus secretion, and ion permeability and transport. Threshold mucus transport occurred at 1 wk of age when 20-25% of the surface cells are ciliated. The neonatal ferret appears to be a useful model for assessing integrated epithelial structure-function relationships that are important not only during early development but also during repair after airway injury involving deciliation.

  5. Postnatal development of phrenic motoneurons in the cat.

    PubMed

    Cameron, W E; Brozanski, B S; Guthrie, R D

    1990-01-01

    The postnatal growth of phrenic motoneurons in the cat was studied using retrograde transport of horseradish peroxidase (HRP). The mean somal surface area of these developing motoneurons increased 2.5 times from day 3 to adult while the mean somal volume increased four-fold. This change in mean somal surface area during postnatal development was found to be correlated with the change in mean axonal conduction velocity measured from phrenic motoneurons.

  6. Longitudinal regression analysis of spatial-temporal growth patterns of geometrical diffusion measures in early postnatal brain development with diffusion tensor imaging.

    PubMed

    Chen, Yasheng; An, Hongyu; Zhu, Hongtu; Jewells, Valerie; Armao, Diane; Shen, Dinggang; Gilmore, John H; Lin, Weili

    2011-10-15

    Although diffusion tensor imaging (DTI) has provided substantial insights into early brain development, most DTI studies based on fractional anisotropy (FA) and mean diffusivity (MD) may not capitalize on the information derived from the three principal diffusivities (e.g. eigenvalues). In this study, we explored the spatial and temporal evolution of white matter structures during early brain development using two geometrical diffusion measures, namely, linear (Cl) and planar (Cp) diffusion anisotropies, from 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects. The growth trajectories were estimated with generalized estimating equations (GEE) using linear fitting with logarithm of age (days). The presence of the white matter structures in Cl and Cp was observed in neonates, suggesting that both the cylindrical and fanning or crossing structures in various white matter regions may already have been formed at birth. Moreover, we found that both Cl and Cp evolved in a temporally nonlinear and spatially inhomogeneous manner. The growth velocities of Cl in central white matter were significantly higher when compared to peripheral, or more laterally located, white matter: central growth velocity Cl=0.0465±0.0273/log(days), versus peripheral growth velocity Cl=0.0198±0.0127/log(days), p<10⁻⁶. In contrast, the growth velocities of Cp in central white matter were significantly lower than that in peripheral white matter: central growth velocity Cp=0.0014±0.0058/log(days), versus peripheral growth velocity Cp=0.0289±0.0101/log(days), p<10⁻⁶. Depending on the underlying white matter site which is analyzed, our findings suggest that ongoing physiologic and microstructural changes in the developing brain may exert different effects on the temporal evolution of these two geometrical diffusion measures. Thus, future studies utilizing DTI with correlative histological analysis in the study of early brain development are warranted. Copyright

  7. Androgen receptor is expressed in mouse cardiomyocytes at prenatal and early postnatal developmental stages.

    PubMed

    Pedernera, Enrique; Gómora, María José; Meneses, Iván; De Ita, Marlon; Méndez, Carmen

    2017-08-14

    Previous studies show that androgens are involved in hypertrophy and excitability of cardiomyocytes and that their effects are mediated through their receptor. The aim of this study was to evaluate the presence of androgen receptor (AR) in mouse heart during prenatal and early postnatal stages. The expression of AR and related genes, alpha myosin heavy chain -Myh6-, beta myosin heavy chain -Myh7- and atrial natriuretic factor -Nppa- was simultaneously evaluated by semiquantitative RT-PCR. AR was also detected by immunohistochemistry. Androgen receptor mRNA was detected in hearts from 10.5 days post coitum to 16 postnatal days. A higher expression of AR mRNA in atria compared to ventricles was observed in neonatal mouse. A positive correlation between mRNA levels of AR and Nppa was observed in mouse heart at early postnatal development. Androgen receptor expression is similar in males and females during cardiac development. Finally, androgen receptor protein was observed by immunohistochemistry in myocardial cells of atria and ventricles from 12.5 days onwards and restricted after 16.5 days post-coitum to nuclei of cardiomyocytes. Present results provide evidence that androgen receptor is expressed from prenatal stages in mouse heart, supporting the proposition that androgens could be involved in mammalian heart development.

  8. Early postnatal hyperalimentation impairs renal function via SOCS-3 mediated renal postreceptor leptin resistance.

    PubMed

    Alcazar, Miguel Angel Alejandre; Boehler, Eva; Rother, Eva; Amann, Kerstin; Vohlen, Christina; von Hörsten, Stephan; Plank, Christian; Dötsch, Jörg

    2012-03-01

    Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism.

  9. Neurovascular coupling develops alongside neural circuits in the postnatal brain.

    PubMed

    Kozberg, Mariel G; Hillman, Elizabeth M C

    2016-01-01

    In the adult brain, increases in local neural activity are accompanied by increases in regional blood flow. This relationship between neural activity and hemodynamics is termed neurovascular coupling and provides the blood flow-dependent contrast detected in functional magnetic resonance imaging (fMRI). Neurovascular coupling is commonly assumed to be consistent and reliable from birth; however, numerous studies have demonstrated markedly different hemodynamics in the early postnatal brain. Our recent study in J. Neuroscience examined whether different hemodynamics in the immature brain are driven by differences in the underlying spatiotemporal properties of neural activity during this period of robust neural circuit expansion. Using a novel wide-field optical imaging technique to visualize both neural activity and hemodynamics in the mouse brain, we observed longer duration and increasingly complex patterns of neural responses to stimulus as cortical connectivity developed over time. However, imaging of brain blood flow, oxygenation, and metabolism in the same mice demonstrated an absence of coupled blood flow responses in the newborn brain. This lack of blood flow coupling was shown to lead to oxygen depletions following neural activations - depletions that may affect the duration of sustained neural responses and could be important to the vascular patterning of the rapidly developing brain. These results are a step toward understanding the unique neurovascular and neurometabolic environment of the newborn brain, and provide new insights for interpretation of fMRI BOLD studies of early brain development.

  10. Comprehensive gene expression changes associated with mouse postnatal kidney development.

    PubMed

    Wu, Bo; Sahoo, Debashis; Brooks, James D

    2013-06-01

    To provide a portrait of the molecular alterations in renal growth that occur in mice postnatally, we performed gene expression profiling at discrete time points during the first 5 weeks of life. Kidneys were harvested from C57BL/6 mice at embryonic day 19.5, and postnatal days 1, 3, 5, 7, 10, 14, 21, 28 and 35. Total RNA was extracted and gene expression profiling was done using microarrays (Agilent Technologies, Santa Clara, California). Transcripts whose expression levels changed during the study course were identified using StepMiner software (http://chicory.stanford.edu/sahoo/public/StepMiner/). Biological functions of the modulated genes were identified using IPA® software. Postnatal kidney growth and development are associated with widespread changes in gene expression with 6,949 transcripts significantly up-regulated and 6,696 down-regulated during the first 5 weeks of life. Pathway analysis showed progressive down-regulation of pathways associated with cell growth and embryonic development (postnatal days 5 to 7). This was followed by increased expression of transcripts associated with lipid/energy metabolism and molecular transport (postnatal days 10 to 14), and down-regulation of genes related to DNA replication, cell cycle, tissue development, protein trafficking and cell morphology (postnatal days 14 to 21). To our knowledge we report the most comprehensive temporal survey of postnatal kidney development to date. This data set provides a framework for interpreting nephropathy, such as that induced by congenital obstruction. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. IGF-1 Induces GHRH Neuronal Axon Elongation during Early Postnatal Life in Mice

    PubMed Central

    Clemessy, Maud; Heurtier, Victor; Ledent, Tatiana; Robinson, Iain C.; Mollard, Patrice; Epelbaum, Jacques; Meaney, Michael J.; Garel, Sonia; Le Bouc, Yves; Kappeler, Laurent

    2017-01-01

    Nutrition during the perinatal period programs body growth. Growth hormone (GH) secretion from the pituitary regulates body growth and is controlled by Growth Hormone Releasing Hormone (GHRH) neurons located in the arcuate nucleus of the hypothalamus. We observed that dietary restriction during the early postnatal period (i.e. lactation) in mice influences postnatal growth by permanently altering the development of the somatotropic axis in the pituitary gland. This alteration may be due to a lack of GHRH signaling during this critical developmental period. Indeed, underfed pups showed decreased insulin-like growth factor I (IGF-I) plasma levels, which are associated with lower innervation of the median eminence by GHRH axons at 10 days of age relative to normally fed pups. IGF-I preferentially stimulated axon elongation of GHRH neurons in in vitro arcuate explant cultures from 7 day-old normally fed pups. This IGF-I stimulating effect was selective since other arcuate neurons visualized concomitantly by neurofilament labeling, or AgRP immunochemistry, did not significantly respond to IGF-I stimulation. Moreover, GHRH neurons in explants from age-matched underfed pups lost the capacity to respond to IGF-I stimulation. Molecular analyses indicated that nutritional restriction was associated with impaired activation of AKT. These results highlight a role for IGF-I in axon elongation that appears to be cell selective and participates in the complex cellular mechanisms that link underfeeding during the early postnatal period with programming of the growth trajectory. PMID:28076448

  12. Early postnatal nutrition determines adult physical activity and energy expenditure in female mice

    USDA-ARS?s Scientific Manuscript database

    Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1...

  13. Dietary long-chain n-3 PUFA, gut microbiota and fat mass in early postnatal piglet development--exploring a potential interplay.

    PubMed

    Andersen, A D; Mølbak, L; Thymann, T; Michaelsen, K F; Lauritzen, L

    2011-12-01

    Dietary n-3PUFA and gut bacteria, particularly Bacteroidetes, have been suggested to be related to adiposity. We investigated if n-3PUFA affected fat storage and cecal bacteria in piglets. Twenty-four 4-day-old piglets were allocated to formula rich in n-3PUFA (∼3E%) from fish oil (FO) or n-6PUFA from sunflower oil (SO) for 14 days. We assessed body weight, fat accumulation by dual-energy X-ray absorptiometry and microbial molecular fingerprints. Dietary PUFA-composition was reflected in higher erythrocyte n-3PUFA in the FO- than the SO-group (P<0.001). Principal component analysis revealed group differences in the overall microbiotic composition, which involved a larger Bacteroides community in the SO-group (P=0.02). There was no significant difference in body fat percentage and no relationship between fat accumulation and gut Bacteroides. Hence, this study does not support an impact of n-3PUFA or microbiota on fat accumulation during the postnatal maturation period. The impact of dietary PUFA on the gut Bacteroides warrants further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Mitochondrial and peroxisomal fatty acid oxidation capacities increase in the skeletal muscles of young pigs during early postnatal development but are not affected by cold stress.

    PubMed

    Herpin, Patrick; Vincent, Annie; Fillaut, Martine; Bonito, Bruno Piteira; Hocquette, Jean-François

    2003-01-01

    In pigs, the optimal utilization of energy substrates within muscle fibers is a prerequisite of the utmost importance for successful adaptation to extra-uterine life. In the present work we demonstrate that fatty acid (FA) oxidative capacities increased within the first five days of life in piglet skeletal muscle. Mitochondrial FA oxidation capacities increased more in the rhomboideus oxidative than in the longissimus lumborum glycolytic muscle (+114% vs. +62%, P < 0.001). The apparent rate of fatty acid degradation by peroxisomes represents 30 to 40% of total FA oxidation capacities and increased by about 170% (P < 0.001) with age in both muscles. The postnatal enhancement of skeletal muscle oxidative capacities was further supported by a rise in acid-soluble and long-chain acylcamitine tissue levels (+67%, P < 0.01), and plasma levels of albumin (+160%, P < 0.001). Cold stress had no effect on mitochondrial and peroxisomal FA oxidation but greatly enhanced (+61%, P < 0.05) the circulating levels of non-esterified fatty acids at five days of life.

  15. Postnatal lung and metabolic development in two marsupial and four eutherian species

    PubMed Central

    Szdzuy, Kirsten; Zeller, Ulrich; Renfree, Marilyn; Tzschentke, Barbara; Janke, Oliver

    2008-01-01

    Two marsupial species (Monodelphis domestica, Macropus eugenii) and four eutherian species (Mesocricetus auratus, Suncus murinus, Tupaia belangeri and Cavia aperea) were examined to compare and contrast the timing of lung and metabolic development during the postnatal maturation of the mammalian respiratory apparatus. Using light, scanning and transmission electron microscopy, the lung structural changes were correlated with indirect calorimetry to track the metabolic development. Marsupial and eutherian species followed the same pattern of mammalian lung development, but differed in the developmental pace. In the two newborn marsupial species, the lung parenchyma was at the early terminal sac stage, with large terminal air sacs, and the lung developed slowly. In contrast, the newborn eutherian species had more advanced lungs at the late terminal sac stage in altricial species (M. auratus, S. murinus) and at the alveolar stage in precocial species (T. belangeri, C. aperea). Postnatal lung development proceeded rapidly in eutherian species. The marsupial species had a low metabolic rate at birth and achieved adult metabolism late in postnatal development. In contrast, newborn eutherian species had high metabolic rates and reached adult metabolism during the first week of life. The time course of the metabolic development is thus tightly linked to the structural differentiation of the lungs and the timing of postnatal lung development. These differences in the neonatal lung structure and the timing of postnatal lung maturation between marsupial and eutherian species reflect their differing reproductive strategies. PMID:18179474

  16. Proteome dynamics during postnatal mouse corpus callosum development

    PubMed Central

    Son, Alexander I.; Fu, Xiaoqin; Suto, Fumikazu; Liu, Judy S.; Hashimoto-Torii, Kazue; Torii, Masaaki

    2017-01-01

    Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled amino acids in mammals (SILAM). The analyzed corpus callosi had distinct proteomic profiles depending on age, indicating rapid progression of specific molecular events during this period. The proteomic profiles were then segregated into five separate clusters, each with distinct trajectories relevant to their intended developmental functions. Our analysis both confirms many previously-identified proteins in aspects of corpus callosum development, and identifies new candidates in understudied areas of development including callosal axon refinement. We present a valuable resource for identifying new proteins integral to corpus callosum development that will provide new insights into the development and diseases afflicting this structure. PMID:28349996

  17. Parvalbumin expression in visual cortical interneurons depends on neuronal activity and TrkB ligands during an Early period of postnatal development.

    PubMed

    Patz, Silke; Grabert, Jochen; Gorba, Thorsten; Wirth, Marcus J; Wahle, Petra

    2004-03-01

    The differentiation of cortical interneurons is controlled by environmental factors. Here, we describe the role of activity and neurotrophins in regulating parvalbumin (PARV) expression using organotypic cultures (OTC) of rat visual cortex as model system. In OTC, PARV expression was dramatically delayed. The organotypic proportion of approximately 6% PARV neurons was not established before 50-70 DIV, whereas in vivo all neurons are present until P20. Thalamic afferents increased cortical PARV mRNA in OTC, but not to the age-matched in vivo level. During the first 10 DIV, BDNF and NT-4 accelerated PARV mRNA expression in a Trk receptor and MEK2 dependent manner. The BDNF action required PI3 kinase signalling. PARV expression required activity. The proportion of neurons which managed to up-regulate PARV was inversely related to the duration of early transient periods of activity deprivation. Long-term activity-deprived OTC completely failed to up-regulate PARV mRNA. Both TrkB ligands failed to promote PARV expression in activity-deprived OTC. However, a few basket and chandelier neurons were observed, suggesting that the development of class-specific morphological features is activity-independent. Once established, PARV expression became resistant to late-onset activity deprivation. In conclusion, PARV expression depended on activity and TrkB ligands which appear to prime the PARV expression already before its developmental onset.

  18. Glial glycine transporter 1 function is essential for early postnatal survival but dispensable in adult mice.

    PubMed

    Eulenburg, Volker; Retiounskaia, Marina; Papadopoulos, Theofilos; Gomeza, Jesús; Betz, Heinrich

    2010-07-01

    The glycine transporter 1 (GlyT1) is expressed in astrocytes and selected neurons of the mammalian CNS. In newborn mice, GlyT1 is crucial for efficient termination of glycine-mediated inhibitory neurotransmission. Furthermore, GlyT1 has been implicated in the regulation of excitatory N-methyl-D-asparate (NMDA) receptors. To evaluate whether glial and neuronal GlyT1 have distinct roles at inhibitory synapses, we inactivated the GlyT1 gene cell type-specifically using mice carrying floxed GlyT1 alleles GlyT1((+)/+)). GlyT1((+)/(+)) mice expressing Cre recombinase in glial cells developed severe neuromotor deficits during the first postnatal week, which mimicked the phenotype of conventional GlyT1 knock-out mice and are consistent with glycinergic over-inhibition. In contrast, Cre-mediated inactivation of the GlyT1 gene in neuronal cells did not result in detectable motor impairment. Notably, some animals deficient for glial GlyT1 survived the first postnatal week and did not develop neuromotor deficits throughout adulthood, although GlyT1 expression was efficiently reduced. Thus, glial GlyT1 is critical for the regulation of glycine levels at inhibitory synapses only during early postnatal life.

  19. Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development

    SciTech Connect

    Ellis-Hutchings, Robert G.; Cherr, Gary N.; Hanna, Lynn A.; Keen, Carl L. . E-mail: clkeen@ucdavis.edu

    2006-09-01

    In experimental animals fed standard laboratory diets, penta-BDE mixtures can decrease circulating thyroid hormone and liver vitamin A concentrations. A substantial number of pregnant women and their children have marginal vitamin A status, potentially increasing their risk of adverse effects to penta-BDE exposure. The current study investigated the effects of maternal gestational and lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD) 18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams and pups, plasma retinol concentrations and plasma retinol binding protein levels were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating hormone concentrations were high in VAM dams exposed to DE-71, suggesting that marginal vitamin A status enhances the susceptibility to thyroid hormone axis disruption by DE-71. These results support the concept that marginal vitamin A status in pregnant women may increase the risk for PBDE-induced disruptions in vitamin A and thyroid hormone homeostasis.

  20. Postnatal Innate Immune Development: From Birth to Adulthood

    PubMed Central

    Georgountzou, Anastasia; Papadopoulos, Nikolaos G.

    2017-01-01

    It is well established that adaptive immune responses are deficient in early life, contributing to increased mortality and morbidity. The developmental trajectories of different components of innate immunity are only recently being explored. Individual molecules, cells, or pathways of innate recognition and signaling, within different compartments/anatomical sites, demonstrate variable maturation patterns. Despite some discrepancies among published data, valuable information is emerging, showing that the developmental pattern of cytokine responses during early life is age and toll-like receptor specific, and may be modified by genetic and environmental factors. Interestingly, specific environmental exposures have been linked both to innate function modifications and the occurrence of chronic inflammatory disorders, such as respiratory allergies. As these conditions are on the rise, our knowledge on innate immune development and its modulating factors needs to be expanded. Improved understanding of the sequence of events associated with disease onset and persistence will lead toward meaningful interventions. This review describes the state-of-the-art on normal postnatal innate immune ontogeny and highlights research areas that are currently explored or should be further addressed. PMID:28848557

  1. Postnatal development of intrinsic GABAergic rhythms in mouse hippocampus.

    PubMed

    Wong, T; Zhang, X L; Asl, M Nassiri; Wu, C P; Carlen, P L; Zhang, L

    2005-01-01

    The local circuitry of the mammalian limbic cortices, including the hippocampus, is capable of generating spontaneous rhythmic activities of 0.5-4 Hz when isolated in vitro. These rhythmic activities are mediated by synchronous inhibitory postsynaptic potentials in pyramidal neurons as the result of repeated discharges of inhibitory interneurons. As such, they are thought to represent an intrinsic inhibitory rhythm. It is unknown at present whether such a rhythm occurs in the immature rodent hippocampus and, if so, the postnatal time window in which it develops. We explored these issues using our recently developed whole mouse hippocampal isolate preparation in vitro. We found that spontaneous rhythmic field potentials started to emerge in mouse hippocampal isolates around postnatal day 10, stabilized after postnatal day 15 and persisted into adulthood. In postnatal days 11-14 mouse hippocampi, the properties of these rhythmic potentials were in keeping with a CA3-driven, IPSP-based intrinsic network activity. The lack of spontaneous field rhythm in neonatal (postnatal days 2-7) hippocampi cannot be attributed to the excitatory activities mediated by gamma-aminobutyric acid type A (GABA-A) receptors, as chloride-dependent hyperpolarizing inhibitory postsynaptic potentials were detectable in neonatal pyramidal neurons at voltages near resting potentials and pharmacological antagonisms of GABA-A receptors produced robust epileptiform discharges in neonatal hippocampi. High frequency afferent stimulation or applications of 4-aminopyridine at low micromolar concentrations failed to induce persistent field rhythm in neonatal hippocampi, suggesting that an overall weak glutamatergic drive is not the sole causing factor. We suggest that the inhibitory postsynaptic potential-based spontaneous rhythmic field potentials develop in a discrete time window during the second postnatal week in the mouse hippocampus due to a fine-tuning in the structure and function of CA3

  2. Early postnatal diazepam exposure alters sex differences in the rat brain.

    PubMed

    Segovia, S; Pérez-Laso, C; Rodríguez-Zafra, M; Calés, J M; Del Abril, A; De Blas, M R; Collado, P; Valencia, A; Guillamón, A

    1991-06-01

    The volume and neuron number of the sexually dimorphic accessory olfactory bulb and locus coeruleus are altered by early postnatal exposure (from the day of birth to postnatal day 16) to diazepam. After diazepam treatment, both volume and neuron number were decreased in the male accessory olfactory bulb and in the female locus coeruleus. These results indicate that early postnatal diazepam administration can bear gender-dependent teratogenic effects upon sexually dimorphic nuclei and suggest that endogenous benzodiazepines may be involved in the sexual differentiation of the brain.

  3. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    SciTech Connect

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  4. Mucin Production during Prenatal and Postnatal Murine Lung Development

    PubMed Central

    Roy, Michelle G.; Rahmani, Mahdis; Hernandez, Jesus R.; Alexander, Samantha N.; Ehre, Camille; Ho, Samuel B.; Evans, Christopher M.

    2011-01-01

    Mucus is a protective gel that lines respiratory tract surfaces. To identify potential roles for secreted gel–forming mucins in lung development, we isolated murine lungs on embryonic days (E) 12.5–18.5, and postnatal days (PN) days 5, 14, and 28. We measured the mucin gene expression by quantitative RT-PCR, and localization by histochemical and immunohistochemical labeling. Alcian blue/periodic acid–Schiff–positive cells are present from E15.5 through PN28. Muc5b transcripts were abundant at all time points from E14.5 to PN28. By contrast, transcript levels of Muc5ac and Muc2 were approximately 300 and 85,000 times lower, respectively. These data are supported by immunohistochemical studies demonstrating the production and localization of Muc5ac and Muc5b protein. This study indicates that mucin production is prominent in developing murine lungs and that Muc5b is an early, abundant, and persistent marker of bronchial airway secretory cells, thereby implicating it as an intrinsic component of homeostatic mucosal defense in the lungs. PMID:21653907

  5. Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure.

    PubMed

    Inomata, Kei; Taniguchi, Shinji; Yonemoto, Hiroki; Inoue, Takeshi; Kawase, Akihiko; Kondo, Yuichi

    2016-11-01

    Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO2 ) target range (85-92%) from April 2011. Lower SpO2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO2 target range, during the early postnatal stage, increases the risk of DA closure failure. Infants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84-100% in study period 1 and 85-92% in period 2. Eighty-two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. Lower early postnatal oxygen saturation target range increases the risk of DA closure failure. © 2016 Japan Pediatric Society.

  6. Prenatal Exposure to Respiratory Syncytial Virus Alters Postnatal Immunity and Airway Smooth Muscle Contractility during Early-Life Reinfections

    PubMed Central

    Harford, Terri J.; Agrawal, Vandana; Yen-Lieberman, Belinda; Rezaee, Fariba; Piedimonte, Giovanni

    2017-01-01

    Maternal viral infections can have pathological effects on the developing fetus which last long after birth. Recently, maternal-fetal transmission of respiratory syncytial virus (RSV) was shown to cause postnatal airway hyperreactivity (AHR) during primary early-life reinfection; however, the influence of prenatal exposure to RSV on offspring airway immunity and smooth muscle contractility during recurrent postnatal reinfections remains unknown. Therefore, we sought to determine whether maternal RSV infection impairs specific aspects of cell-mediated offspring immunity during early-life reinfections and the mechanisms leading to AHR. Red fluorescent protein-expressing recombinant RSV (rrRSV) was inoculated into pregnant rat dams at midterm, followed by primary and secondary postnatal rrRSV inoculations of their offspring at early-life time points. Pups and weanlings were tested for specific lower airway leukocyte populations by flow cytometry; serum cytokine/chemokine concentrations by multiplex ELISA and neurotrophins concentrations by standard ELISA; and ex vivo lower airway smooth muscle (ASM) contraction by physiological tissue bath. Pups born to RSV-infected mothers displayed elevated total CD3+ T cells largely lacking CD4+ and CD8+ surface expression after both primary and secondary postnatal rrRSV infection. Cytokine/chemokine analyses revealed reduced IFN-γ, IL-2, IL-12, IL-17A, IL-18, and TNF-α, as well as elevated nerve growth factor (NGF) expression. Prenatal exposure to RSV also increased ASM reactivity and contractility during early-life rrRSV infection compared to non-exposed controls. We conclude that maternal RSV infection can predispose offspring to postnatal lower airways dysfunction by altering immunity development, NGF signaling, and ASM contraction during early-life RSV reinfections. PMID:28178290

  7. Radiology of postnatal skeletal development. Pt. 6

    SciTech Connect

    McCarthy, S.M.; Ogden, J.A.

    1982-11-01

    Thirty-six pairs of proximal radioulnar and elbow units from cadavers and prepared skeletons ranging in age from full-term neonates to fourteen years, were studied morphologically and roentgenographically. Air/cartilage interfacing was used to demonstrate the osseous and cartilaginous portions of the developing epiphyses. These roentgenographic aspects are discussed and illustrated to provide a reference index. The skeletal development is outlined with regard to the diagnosis of several traumatic skeletal diseases as dislocation of elbow or radial head. Moteggia fracture dislocation and Nursemaid's elbow.

  8. Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

    PubMed

    Martin, J H; Donarummo, L; Hacking, A

    2000-02-01

    This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous

  9. Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat kidneys.

    PubMed

    Hasan, Jamal; Beharry, Kay D; Gharraee, Zahra; Stavitsky, Yuri; Abad-Santos, Patricia; Abad-Santos, Matthew; Aranda, Jacob V; Modanlou, Houchang D

    2008-03-01

    The use of indomethacin in preterm newborn infants with symptomatic patent ductus arteriosus is associated with compromised renal function. Ibuprofen has been shown to be as effective as indomethacin with fewer renal side effects. We examined the hypothesis that early postnatal ibuprofen has less adverse effects on neonatal rat renal prostanoids, COX-2 expression, and angiotensin II than indomethacin. Newborn rats received IP injections of human therapeutic doses of ibuprofen or indomethacin on the first 3 days of life. Control rats were treated with equivalent volume saline. Kidneys were assessed in suckling and weanling rats for prostanoids, COX-2 expression, and angiotensin II. In suckling rats, indomethacin suppressed PGE(2) and COX-2 expression, and increased PGF(2alpha), whereas ibuprofen increased COX-2 and angiotensin II. Although both NSAIDs suppressed 6-ketoPGF(1alpha) and TxB(2) levels in suckling rats, the effect was sustained in weanling rats with indomethacin. Our findings demonstrate that indomethacin exhibits more potent suppressive effects on renal COX-2 and vasodilator prostanoids which are important regulators of renal development and function. These long-term, sustained effects may explain in part, why indomethacin exerts more severe adverse renal effects than ibuprofen, when administered during early postnatal life.

  10. Postnatal development of lung T lymphocytes in a porcine model.

    PubMed

    Balam-May, Angel J; Ramírez-Estudillo, Carmen; Lazo-Vázquez, Gloria; Vega-López, Marco A

    2014-10-01

    Despite the high prevalence of respiratory diseases in the world and the extensive information available on the mucosal immune system, research on the development of the lung immune system in humans is limited by technical and ethical considerations; therefore, we studied the postnatal development of T lymphocytes in lung lobes in a porcine model. Using less than 36-hour-old (NB), 1-week-weaned (5-week-old -AW-), 3-month-old (3M), and 4-year-old (4YR) healthy, nonvaccinated, specific pathogen free (SPF) Vietnamese miniature pigs, we studied the CD3+, CD4+, CD8+, TCR1 (gamma-delta T cells), and CD25+ (IL-2R-alpha) cell subpopulations in lung lobes parenchyma, bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMC), and cervical lymph nodes (LN) by flow cytometry. No differences among lung lobes were detected in any of the cell subpopulations tested. A low proportion of T cell subsets was detected in NB and 4YR groups in lung and BAL. Besides, the AW and 3M groups showed important changes in T cell subpopulations. These results suggest that in healthy animals the lung lobes behave as a homogeneous immune organ. T cells were detected in very low percentages at birth and in adult life, which may explain the high susceptibility to respiratory infections both early and later in life. Postweaning antigenic challenges and endocrine and sexual maturity at 3M had important effects on the development of the mucosal immune system. It was also evident that changes at mucosal sites were poorly correlated with PBMC and LN.

  11. Allelic specificity of Ube3a expression in the mouse brain during postnatal development.

    PubMed

    Judson, Matthew C; Sosa-Pagan, Jason O; Del Cid, Wilmer A; Han, Ji Eun; Philpot, Benjamin D

    2014-06-01

    Genetic alterations of the maternal UBE3A allele result in Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, lack of speech, and difficulty with movement and balance. The combined effects of maternal UBE3A mutation and cell type-specific epigenetic silencing of paternal UBE3A are hypothesized to result in a complete loss of functional UBE3A protein in neurons. However, the allelic specificity of UBE3A expression in neurons and other cell types in the brain has yet to be characterized throughout development, including the early postnatal period when AS phenotypes emerge. Here we define maternal and paternal allele-specific Ube3a protein expression throughout postnatal brain development in the mouse, a species that exhibits orthologous epigenetic silencing of paternal Ube3a in neurons and AS-like behavioral phenotypes subsequent to maternal Ube3a deletion. We find that neurons downregulate paternal Ube3a protein expression as they mature and, with the exception of neurons born from postnatal stem cell niches, do not express detectable paternal Ube3a beyond the first postnatal week. By contrast, neurons express maternal Ube3a throughout postnatal development, during which time localization of the protein becomes increasingly nuclear. Unlike neurons, astrocytes and oligodendrotyes biallelically express Ube3a. Notably, mature oligodendrocytes emerge as the predominant Ube3a-expressing glial cell type in the cortex and white matter tracts during postnatal development. These findings demonstrate the spatiotemporal characteristics of allele-specific Ube3a expression in key brain cell types, thereby improving our understanding of the developmental parameters of paternal Ube3a silencing and the cellular basis of AS. Copyright © 2013 Wiley Periodicals, Inc.

  12. Effect of early postnatal exposure to polychlorinated biphenyls (PCBs) on fertility in male rats

    SciTech Connect

    Sager, D.B.; Shih-Schroeder, W.; Girard, D.

    1987-06-01

    Males exposed to PCBs during lactation exhibited reduced fertility, i.e., reduced incidence of implantation in normal females mated to experimental males. However, a reduced weight gain during the time of treatment in the pups exposed to the higher doses of PCBs was also observed. After treatment, weight gain was comparable or greater in the experimental pups and by the time of mating and autopsy, body weights in all groups were comparable. The present experiments were designed 1) to determine if the early reduced weight gain (previously observed) has any influence on fertility, and 2) to investigate the effect of early postnatal exposure to PCBs on sperm counts and the ability of the sperm to support normal development.

  13. Fine structural aspects of postnatal development of feline lung.

    PubMed

    al-Tikriti, M S; Henry, R W; Eiler, H; Schultz, T W; Breider, M A; Cullens, W C

    1991-12-01

    Lung development was studied in late prenatal, 1-, 7-, 14-, and 21-days postnatal and adult cats. Cats were born with a few alveoli, and the lungs appeared to have patches of primitive air spaces (saccules). The saccules of prenatal kittens were thick walled, very cellular, and lined by type II pneumocytes. Eosinophils were observed in the septum, intraepithelially, and in the alveolar space of growing cats. Secondary septa were flanked by a double capillary network and divided saccules into multiple shallow alveoli. Septation was irregular and time dependent and not completed by day 231 of postnatal life. Elastic fibers accumulated at the tip of the septa, seemingly playing an important role in alveolar formation. Type II pneumocytes were located at the base of the secondary septa in growing cats, thus strengthening secondary septa to withstand the stresses of respiration. Pores of Kohn were not observed in growing cats.

  14. [Histomorphology of the suslik ovary during postnatal development and hibernation].

    PubMed

    Khadzhiolov, A I; Tsarvulkova-Denkova, R T

    1977-10-01

    Morphogenetic and histogenetic changes in the ovaries of Citellus citellus during the postnatal period and hibernation (September- March) at the age of 10, 25, 45 days and 2 to 12 months after birth were studied. Significant cellular and tissue-organoid differentiation processes were established. After birth oogonia enter the prophase I of meiotic division. At the end of the first month, oocytes with enlarged cytoplasm and single layer of satellite cells form the primary follicles. The growing follicles with organizing antrum are formed in the third postnatal month. During the same time, theca foliculi is observed. Between the 3d and the 6th months after birth the authors demonstrate a "stage ox isofolliculia" when the follicles stop undergoing further development. During the winter hibernation, the ovarian follicles continue to grow slowly and at the end of this period, preovulatory follicles are formed. The results reported demonstrate Citellus citellus ovary to be an organ of intensive cell-tissue reconstruction during the postnatal development and hibernation period determined by the ovarian histophysiology, the ovarian steroid hormones production and the hormonal activity of other glands and organs of the endocrine system.

  15. Oligodendrogenesis and myelinogenesis during postnatal development effect of glatiramer acetate.

    PubMed

    From, Renana; Eilam, Raya; Bar-Lev, Dekel D; Levin-Zaidman, Smadar; Tsoory, Michael; LoPresti, Patrizia; Sela, Michael; Arnon, Ruth; Aharoni, Rina

    2014-04-01

    Myelinogenesis in the mammal nervous system occurs predominantly postnatally. Glatiramer acetate (GA), a drug for the treatment for multiple sclerosis (MS), has been shown to induce immunomodulation and neuroprotection in the inflamed CNS in MS and in experimental autoimmune encephalomyelitis (EAE). Here we investigated whether GA can affect myelinogenesis and oligodendrogenesis in the developing nervous system under nonpathological conditions. Towards this end we studied myelination in mice injected daily by GA, at postnatal Days 7-21. Immunohistological and ultrastructural analyses revealed significant elevation in the number of myelinated axons as well as in the thickness of the myelin encircling them and their resulting g-ratios, in spinal cords of GA-injected mice compared with their PBS-injected littermates, at postnatal Day 14. Elevation in myelinated axons was detected also in the peripheral ventral roots of the motor nerves. GA induced also an increase in axonal diameter, implying an effect on the overall development of the nervous system. A prominent elevation in the amount of progenitor oligodendrocytes and their BrdU incorporation, as well as in mature oligodendrocytes indicated that the effect of GA is linked to increased proliferation and differentiation along the oligodendroglial maturation cascade. In addition, elevation in insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) was found in the white matter of the GA-injected mice. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates at postnatal Day 21. These cumulative findings corroborate the beneficial effect of GA on oligodendrogenesis and myelination.

  16. Growth abnormalities in the population exposed in utero and early postnatally to polychlorinated biphenyls and dibenzofurans

    SciTech Connect

    Yueliang L. Guo; Chen-Chin Hsu; Lambert, G.H.

    1995-09-01

    This article reviews the findings in children exposed to various levels of polychlorinated biphenyls (PCBs) and related compounds in utero and early postnatally. Yu-Cheng ({open_quotes}oil-disease{close_quotes}) mothers were Taiwanese women exposed to PCBs and their heat-degradation products form the ingestion of contaminated rice oil in 1979. Children of these mothers were born growth retarded, with dysmorphic physical findings, and delayed cognitive development compared with unexposed children. In this article, findings in Yu-Cheng children born between 1978 and 1985 are summarized and compared with two other well-documented cohorts of children prenatally exposed to different levels of PCBs. Results of the investigation in Yu-Cheng children will provide important information about the toxicities, health effects, and mechanisms of PCB/PCDF exposure and demonstrate that the developing human is more sensitive than the adult to the toxic effects of these chemicals. 53 refs., 2 tabs.

  17. Prenatal stress alters microglial development and distribution in postnatal rat brain.

    PubMed

    Gómez-González, Beatriz; Escobar, Alfonso

    2010-03-01

    Stress affects microglial function and viability during adulthood and early postnatal life; however, it is unknown whether stress to the pregnant dam might alter offspring microglia. The effects of prenatal stress on microglial development and distribution in the postnatal brain were studied using Wistar rats. Prenatal stress consisting of 20 min of forced swimming occurred on embryonic days 10-20. On postnatal days 1 and 10, stressed and control pups were killed. Microglia were identified using Griffonia simplicifolia lectin and quantified in the whole encephalon. In addition, plasma corticosterone was measured in dams at embryonic day 20, and in pups on postnatal days 1 and 10. At postnatal day 1, there was an increase in number of ramified microglia in the parietal, entorhinal and frontal cortices, septum, basal ganglia, thalamus, medulla oblongata and internal capsule in the stressed pups as compared to controls, but also there was a reduction of amoeboid microglia and the total number of microglia in the corpus callosum. By postnatal day 10, there were no differences in the morphologic type or the distribution of microglia between the prenatal stress and control groups, except in the corpus callosum; where prenatal stress decreased the number of ramified microglia. The stress procedure was effective in producing plasma rise in corticosterone levels of pregnant rats at embryonic day 20 when compared to same age controls. Prenatal stress reduced the number of immature microglia and promoted an accelerated microglial differentiation into a ramified form. These findings may be related to an increase in plasma corticosterone in the pregnant dam.

  18. Postnatal Development of the Corticospinal Tract in the Reeler Mouse.

    PubMed

    Namikawa, Tomohiro; Kikkawa, Satoshi; Inokuchi, Go; Terashima, Toshio

    2015-12-03

    Corticospinal tract (CST) neurons are dislocated in the motor cortex of Reelin-deficient mouse, reeler. In the present study, we examined whether postnatal axonal growth arising from these dislocated CST neurons are normal or not with use of anterograde tracer, DiI and retrograde tracer, HRP. A single injection of DiI into the motor cortex of the normal and reeler mice was made during postnatal period and 8-24 hours later, the animals were sacrificed to examine DiI-labeled CST axons at the lower medulla and spinal cord. Both in the normal and reeler mice, CST axons arrived at the pyramidal decussation and entered into the contralateral spinal cord around on postnatal day (P) 0.5, and descend in the ventral area of the contralateral dorsal funiculus at C2 level on P2, at C8 level on P3, at the mid-thoracic level on P4, and at the upper lumbar level on P8. The similar results were also demonstrated by the retrograde labeling of CST neurons with injection of HRP into the C1 level or upper lumbar enlargement. Next, we examined CaMKIIα expression in the CST axons of the adult normal and reeler mice. CaMKIIα-immunopositive fibers were recognized throughout the CST pathway from the internal capsule to the dorsal funiculus of the spinal cord both in the normal and reeler mice. The present study has demonstrated that ectopic location of cell bodies of reeler CST neurons do not affect postnatal development of CST axons in the spinal cord.

  19. Heart rate variability in kittens during early postnatal ontogeny.

    PubMed

    Fateev, M M; Nikolaeva, T N; Dashichev, K V; Olendar, N V

    2009-06-01

    Heart rate variability in awake kittens under resting conditions was studied during the following periods of postnatal ontogeny: newborn animals, 10-day-old animals (eye opening), 20-day-old animals (rise on the legs), and 30-day-old animals (control). Newborn animals were characterized by high activity of the sympathoadrenal system due to birth stress. The effect of stress factors increased in 10-day-old kittens, which was related to the start of functioning of distant receptors and delivery of new environmental information into the brain. The acquisition of upright posture and locomotion on the limbs were accompanied by activation of the vagus nerve in kittens. Significant changes in temporal, geometric, and spectral characteristics illustrate an increase in adaptability of the organism and possibility for independent living (particularly, by the 30th day of life).

  20. Molecular and functional heterogeneity of early postnatal porcine satellite cell populations is associated with bioenergetic profile.

    PubMed

    Miersch, Claudia; Stange, Katja; Hering, Silvio; Kolisek, Martin; Viergutz, Torsten; Röntgen, Monika

    2017-03-27

    During postnatal development, hyperplastic and hypertrophic processes of skeletal muscle growth depend on the activation, proliferation, differentiation, and fusion of satellite cells (SC). Therefore, molecular and functional SC heterogeneity is an important component of muscle plasticity and will greatly affect long-term growth performance and muscle health. However, its regulation by cell intrinsic and extrinsic factors is far from clear. In particular, there is only minor information on the early postnatal period which is critical for muscle maturation and the establishment of adult SC pools. Here, we separated two SC subpopulations (P40/50, P50/70) from muscle of 4-day-old piglets. Our results characterize P40/50 as homogeneous population of committed (high expression of Myf5), fast-proliferating muscle progenitors. P50/70 constituted a slow-proliferating phenotype and contains high numbers of differentiated SC progeny. During culture, P50/70 is transformed to a population with lower differentiation potential that contains 40% Pax7-positive cells. A reversible state of low mitochondrial activity that results from active down-regulation of ATP-synthase is associated with the transition of some of the P50/70 cells to this more primitive fate typical for a reserve cell population. We assume that P40/50 and P50/70 subpopulations contribute unequally in the processes of myofiber growth and maintenance of the SC pool.

  1. Molecular and functional heterogeneity of early postnatal porcine satellite cell populations is associated with bioenergetic profile

    PubMed Central

    Miersch, Claudia; Stange, Katja; Hering, Silvio; Kolisek, Martin; Viergutz, Torsten; Röntgen, Monika

    2017-01-01

    During postnatal development, hyperplastic and hypertrophic processes of skeletal muscle growth depend on the activation, proliferation, differentiation, and fusion of satellite cells (SC). Therefore, molecular and functional SC heterogeneity is an important component of muscle plasticity and will greatly affect long-term growth performance and muscle health. However, its regulation by cell intrinsic and extrinsic factors is far from clear. In particular, there is only minor information on the early postnatal period which is critical for muscle maturation and the establishment of adult SC pools. Here, we separated two SC subpopulations (P40/50, P50/70) from muscle of 4-day-old piglets. Our results characterize P40/50 as homogeneous population of committed (high expression of Myf5), fast-proliferating muscle progenitors. P50/70 constituted a slow-proliferating phenotype and contains high numbers of differentiated SC progeny. During culture, P50/70 is transformed to a population with lower differentiation potential that contains 40% Pax7-positive cells. A reversible state of low mitochondrial activity that results from active down-regulation of ATP-synthase is associated with the transition of some of the P50/70 cells to this more primitive fate typical for a reserve cell population. We assume that P40/50 and P50/70 subpopulations contribute unequally in the processes of myofiber growth and maintenance of the SC pool. PMID:28344332

  2. Multiple roles for the endocannabinoid system during the earliest stages of life: pre- and postnatal development.

    PubMed

    Fride, E

    2008-05-01

    The endocannabinoid system, including its receptors (CB(1) and CB(2)), endogenous ligands ('endocannabinoids'), synthesising and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. In addition, the endocannabinoids, notably 2-arachidonyl glycerol, are also present in maternal milk. During three distinct developmental stages (i.e. embryonic implantation, prenatal brain development and postnatal suckling), the endocannabinoid system appears to play an essential role for development and survival. Thus, during early pregnancy, successful embryonic passage through the oviduct and implantation into the uterus both require critical enzymatic control of optimal anandamide levels at the appropriate times and sites. During foetal life, the cannabinoid CB(1) receptor plays a major role in brain development, regulating neural progenitor differentiation into neurones and glia and guiding axonal migration and synaptogenesis. Postnatally, CB(1) receptor blockade interferes with the initiation of milk suckling in mouse pups, by inducing oral motor weakness, which exposes a critical role for CB(1) receptors in the initiation of milk suckling by neonates, possibly by interfering with innervation of the tongue muscles. Manipulating the endocannabinoid system by pre- and/or postnatal administration of cannabinoids or maternal marijuana consumption, has significant, yet subtle effects on the offspring. Thus, alterations in the dopamine, GABA and endocannabinoid systems have been reported while enhanced drug seeking behaviour and impaired executive (prefrontal cortical) function have also been observed. The relatively mild nature of the disruptive effects of prenatal cannabinoids may be understood in the framework of the intricate timing requirements and frequently biphasic effects of the (endo)cannabinoids. In conclusion, the endocannabinoid system plays several key roles

  3. Postnatal development of fiber type composition in rabbit jaw and leg muscles.

    PubMed

    Korfage, J A M; Helmers, R; Matignon, M de Goüyon; van Wessel, T; Langenbach, G E J; van Eijden, T M G J

    2009-01-01

    We examined the difference in fiber type composition and cross-sectional areas during postnatal development in male rabbit jaw muscles and compared these with changes in leg muscles. The myosin heavy chain (MyHC) content of the fibers was determined by immunohistochemistry. No fiber type difference was found between the jaw muscles in 20-week-old rabbits. However, the way this adult fiber type composition was reached differed between the muscles. The deep temporalis, medial pterygoid, and superficial masseter displayed an increase in alpha fibers during early and a decrease during late postnatal development. Other jaw muscles displayed an increase in alpha fibers during early development only. In contrast, alpha fibers were not found in the soleus, in which fiber type changes were completed at week 4. The gastrocnemius muscle did not change its fiber type composition. Initially, fibers in jaw-opening muscles had larger cross-sectional areas than in other muscles, but they increased less during development. Although there were no large differences in the fiber type composition of muscles in young adult rabbits, large differences were found in the jaw muscles, but not in the leg muscles, during development. In part, these developmental changes in fiber percentages within the jaw muscles can be explained by functional modifications in this muscle group. In the present study, the deep temporalis, medial pterygoid, and superficial masseter showed the most dramatic percent changes in fibers during postnatal development. (c) 2008 S. Karger AG, Basel.

  4. A comparative study of embryonic development of some bird species with different patterns of postnatal growth.

    PubMed

    Blom, Jonas; Lilja, Clas

    2005-01-01

    Some studies show that birds with high postnatal growth rates (e.g. altricial species) are characterized by a rapid early development of "supply" organs, such as digestive organs. Birds with low postnatal growth rates (e.g. precocial species) exhibit a slower early development of these organs and a more rapid early development of other "demand" organs, such as brain, muscles, skeleton and feathers. To test whether these differences can be traced back to early embryonic development and whether they can be associated with changes in developmental timing, i.e. heterochrony, we compared embryos of the precocial quail and the altricial fieldfare, two bird species with low and high postnatal growth rates, respectively. We used classical staging techniques that use developmental landmarks to categorize embryonic maturity as well as morphological measurements. These techniques were combined with immune detection of muscle specific proteins in the somites. Our data showed that the anlagen of the head, brain and eyes develop earlier in the quail than in the fieldfare in contrast to the gut which develops earlier in the fieldfare than in the quail. Our data also showed that the quail and the fieldfare displayed different rates of myotome formation in the somites which contribute to muscle formation in the limbs and thorax. We believe these observations are connected with important differences in neonatal characteristics, such as the size of the brain, eyes, organs for locomotion and digestion. This leads us to the conclusion that selection for late ontogenetic characteristics can alter early embryonic development and that growth rate is of fundamental importance for the patterning of avian embryonic development. It also appears that this comparative system offers excellent opportunities to test hypotheses about heterochrony.

  5. Intestinal expression of TFF and related genes during postnatal development in a piglet probiotic trial.

    PubMed

    Scholven, Jutta; Taras, David; Sharbati, Soroush; Schön, Jennifer; Gabler, Christoph; Huber, Otmar; Meyer zum Büschenfelde, Dirk; Blin, Nikolaus; Einspanier, Ralf

    2009-01-01

    Trefoil factor family (TFF) peptides provide protective and reparative effects by enhancing epithelial integrity and promoting mucosal restitution. TFF peptide expression is induced after mucosal damage. These processes are of central physiological relevance during the postnatal intestinal development and are strongly influenced during the weaning period. In piglets, weaning at early maturation stages frequently causes mucosal inflammation. The aim of this study was to evaluate postnatal intestinal TFF expression in a piglet probiotic trial. Low intestinal TFF2 expression was measured at early maturation stages. Weaning, however, was associated with a distinct response of increased TFF2 expression, indicating an important role in enhancing mucosal integrity. In the distal jejunum and ileum weaning could as well be associated with increased TFF3 mRNA levels. Differential TFF1 expression was not detected. Furthermore, TFF2 localization studies in different intestinal loci were performed by means of immunohistochemistry. Expression of selected genes (TGFA, EGFR, Cox-2) known to promote TFF signaling showed differential expression pattern as well, thereby providing further functional background. Furthermore, the expression patterns of EGFR observed in this study contribute to an advanced view of previous findings of EGFR regulation mainly obtained in rodents. An upregulated EGFR expression during early postnatal development suggests a local relevance to porcine intestinal maturation. However, a feed supplementation with the probiotic strain Enterococcus faecium did not influence TFF expression.

  6. Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats.

    PubMed

    Amaral, Cristiane; Antonio, Bruno; Oliveira, Maria Gabriela Menezes; Hamani, Clement; Guinsburg, Ruth; Covolan, Luciene

    2015-11-01

    Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory.

  7. Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice

    PubMed Central

    Li, Ge; Kohorst, John J.; Zhang, Wenjuan; Laritsky, Eleonora; Kunde-Ramamoorthy, Govindarajan; Baker, Maria S.; Fiorotto, Marta L.; Waterland, Robert A.

    2013-01-01

    Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1 (P1), mice were fostered in control (C) or small litters (SL). SL mice had increased body weight and adiposity at weaning (P21), which persisted to adulthood (P180). Detailed metabolic studies indicated that female adult SL mice have decreased physical activity and energy expenditure but not increased food intake. Genome-scale DNA methylation profiling identified extensive changes in hypothalamic DNA methylation during the suckling period, suggesting that it is a critical period for developmental epigenetics in the mouse hypothalamus. Indeed, SL mice exhibited subtle and sex-specific changes in hypothalamic DNA methylation that persisted from early life to adulthood, providing a potential mechanistic basis for the sustained physiological effects. Expression profiling in adult hypothalamus likewise provided evidence of widespread sex-specific alterations in gene expression. Together, our data indicate that early postnatal overnutrition leads to a reduction in spontaneous physical activity and energy expenditure in females and suggest that early postnatal life is a critical period during which nutrition can affect hypothalamic developmental epigenetics. PMID:23545705

  8. Glycine receptor heterogeneity in rat spinal cord during postnatal development.

    PubMed Central

    Becker, C M; Hoch, W; Betz, H

    1988-01-01

    Two different isoforms of the inhibitory glycine receptor were identified during postnatal development of rat spinal cord. A neonatal form characterized by low strychnine binding affinity, altered antigenicity, and a ligand binding subunit differing in mol. wt (49 kd) from that of the adult receptor (48 kd) predominates at birth (70% of the total receptor protein). Separation from the adult form could be achieved by either use of a selective antibody or glycine gradient elution of 2-aminostrychnine affinity columns. Both isoforms co-purify with the mol. wt 93 kd peripheral membrane protein of the postsynaptic glycine receptor complex. Images PMID:2850172

  9. Myelin-associated glycoprotein modulates apoptosis of motoneurons during early postnatal development via NgR/p75(NTR) receptor-mediated activation of RhoA signaling pathways.

    PubMed

    Palandri, A; Salvador, V R; Wojnacki, J; Vivinetto, A L; Schnaar, R L; Lopez, P H H

    2015-09-03

    Myelin-associated glycoprotein (MAG) is a minor constituent of nervous system myelin, selectively expressed on the periaxonal myelin wrap. By engaging multiple axonal receptors, including Nogo-receptors (NgRs), MAG exerts a nurturing and protective effect the axons it ensheaths. Pharmacological activation of NgRs has a modulatory role on p75(NTR)-dependent postnatal apoptosis of motoneurons (MNs). However, it is not clear whether this reflects a physiological role of NgRs in MN development. NgRs are part of a multimeric receptor complex, which includes p75(NTR), Lingo-1 and gangliosides. Upon ligand binding, this multimeric complex activates RhoA/ROCK signaling in a p75(NTR)-dependent manner. The aim of this study was to analyze a possible modulatory role of MAG on MN apoptosis during postnatal development. A time course study showed that Mag-null mice suffer a loss of MNs during the first postnatal week. Also, these mice exhibited increased susceptibility in an animal model of p75(NTR)-dependent MN apoptosis induced by nerve-crush injury, which was prevented by treatment with a soluble form of MAG (MAG-Fc). The protective role of MAG was confirmed in in vitro models of p75(NTR)-dependent MN apoptosis using the MN1 cell line and primary cultures. Lentiviral expression of shRNA sequences targeting NgRs on these cells abolished protection by MAG-Fc. Analysis of RhoA activity using a FRET-based RhoA biosensor showed that MAG-Fc activates RhoA. Pharmacological inhibition of p75(NTR)/RhoA/ROCK pathway, or overexpression of a p75(NTR) mutant unable to activate RhoA, completely blocked MAG-Fc protection against apoptosis. The role of RhoA/ROCK signaling was further confirmed in the nerve-crush model, where pretreatment with ROCK inhibitor Y-27632 blocked the pro-survival effect of MAG-Fc. These findings identify a new protective role of MAG as a modulator of apoptosis of MNs during postnatal development by a mechanism involving the p75(NTR)/RhoA/ROCK signaling pathway

  10. Myelin-associated glycoprotein modulates apoptosis of motoneurons during early postnatal development via NgR/p75NTR receptor-mediated activation of RhoA signaling pathways

    PubMed Central

    Palandri, A; Salvador, V R; Wojnacki, J; Vivinetto, A L; Schnaar, R L; Lopez, P H H

    2015-01-01

    Myelin-associated glycoprotein (MAG) is a minor constituent of nervous system myelin, selectively expressed on the periaxonal myelin wrap. By engaging multiple axonal receptors, including Nogo-receptors (NgRs), MAG exerts a nurturing and protective effect the axons it ensheaths. Pharmacological activation of NgRs has a modulatory role on p75NTR-dependent postnatal apoptosis of motoneurons (MNs). However, it is not clear whether this reflects a physiological role of NgRs in MN development. NgRs are part of a multimeric receptor complex, which includes p75NTR, Lingo-1 and gangliosides. Upon ligand binding, this multimeric complex activates RhoA/ROCK signaling in a p75NTR-dependent manner. The aim of this study was to analyze a possible modulatory role of MAG on MN apoptosis during postnatal development. A time course study showed that Mag-null mice suffer a loss of MNs during the first postnatal week. Also, these mice exhibited increased susceptibility in an animal model of p75NTR-dependent MN apoptosis induced by nerve-crush injury, which was prevented by treatment with a soluble form of MAG (MAG-Fc). The protective role of MAG was confirmed in in vitro models of p75NTR-dependent MN apoptosis using the MN1 cell line and primary cultures. Lentiviral expression of shRNA sequences targeting NgRs on these cells abolished protection by MAG-Fc. Analysis of RhoA activity using a FRET-based RhoA biosensor showed that MAG-Fc activates RhoA. Pharmacological inhibition of p75NTR/RhoA/ROCK pathway, or overexpression of a p75NTR mutant unable to activate RhoA, completely blocked MAG-Fc protection against apoptosis. The role of RhoA/ROCK signaling was further confirmed in the nerve-crush model, where pretreatment with ROCK inhibitor Y-27632 blocked the pro-survival effect of MAG-Fc. These findings identify a new protective role of MAG as a modulator of apoptosis of MNs during postnatal development by a mechanism involving the p75NTR/RhoA/ROCK signaling pathway. Also, our results

  11. Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance.

    PubMed

    Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Lopez-Bote, Clemente J; Sanchez-Sanchez, Raul; Perez-Solana, Maria L; Torres-Rovira, Laura; Ayuso, Miriam; Gonzalez, Jorge

    2014-10-01

    Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity.

  12. Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

    PubMed

    Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

    2016-05-01

    The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  13. Non-imprinted epigenetics in fetal and postnatal development and growth.

    PubMed

    Godfrey, Keith M; Lillycrop, Karen A; Burdge, Graham C; Gluckman, Peter D; Hanson, Mark A

    2013-01-01

    Recent evidence demonstrates that the environment in early life can have important effects on fetal and postnatal growth, on development and on risk of developing common non-communicable diseases in later life. In animals, the environment during early life induces altered phenotypes in ways which are influenced or mediated by epigenetic mechanisms. The latter include DNA methylation, covalent modifications of histones and non-coding RNAs. Most is known about DNA methylation changes, which are gene specific, include effects on non-imprinted genes and function at the level of individual CpG dinucleotides to alter gene expression. Preliminary evidence from human studies suggests a similar important role for epigenetic processes. Tuning of phenotype by the developmental environment has adaptive value because it attempts to match an individual's responses to the environment predicted to be experienced later; hence, such processes have been selected during evolution as conferring fitness advantage. When the phenotype is mismatched, e.g. from inaccurate nutritional cues from the mother or placenta before birth, or from rapid environmental change through improved socioeconomic conditions, risk of non-communicable diseases increases. Evidence is accruing that endocrine or nutritional interventions during early postnatal life can reverse epigenetic and phenotypic changes induced, for example, by unbalanced maternal diet during pregnancy. Elucidation of epigenetic processes may enable early intervention strategies to improve early development and growth. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  14. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

    PubMed

    Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

    2016-01-01

    Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb.

  15. Early postnatal respiratory viral infection induces structural and neurochemical changes in the neonatal piglet brain.

    PubMed

    Conrad, Matthew S; Sutton, Bradley P; Larsen, Ryan; Van Alstine, William G; Johnson, Rodney W

    2015-08-01

    Infections that cause inflammation during the postnatal period are common, yet little is known about their impact on brain development in gyrencephalic species. To address this issue, we investigated brain development in domestic piglets which have brain growth and morphology similar to human infants, after experimentally infecting them with porcine reproductive and respiratory syndrome virus (PRRSV) to induce an interstitial pneumonia Piglets were inoculated with PRRSV on postnatal day (PD) 7 and magnetic resonance imaging (MRI) was used to assess brain macrostructure (voxel-based morphometry), microstructure (diffusion tensor imaging) and neurochemistry (MR-spectroscopy) at PD 29 or 30. PRRSV piglets exhibited signs of infection throughout the post-inoculation period and had elevated plasma levels of TNFα at the end of the study. PRRSV infection increased the volume of several components of the ventricular system including the cerebral aqueduct, fourth ventricle, and the lateral ventricles. Group comparisons between control and PRRSV piglets defined 8 areas where PRRSV piglets had less gray matter volume; 5 areas where PRRSV piglets had less white matter volume; and 4 relatively small areas where PRRSV piglets had more white matter. Of particular interest was a bilateral reduction in gray and white matter in the primary visual cortex. PRRSV piglets tended to have reduced fractional anisotropy in the corpus callosum. Additionally, N-acetylaspartate, creatine, and myo-inositol were decreased in the hippocampus of PRRSV piglets suggesting disrupted neuronal and glial health and energy imbalances. These findings show in a gyrencephalic species that early-life infection can affect brain growth and development.

  16. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits

    PubMed Central

    Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

    2016-01-01

    Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

  17. Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males.

    PubMed

    Chiba, Junko; Suzuki, Hiroetsu; Aoyama, Hiroaki; Katayama, Kentaro; Suzuki, Katsushi

    2011-04-01

    The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells.

  18. Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats

    PubMed Central

    Dai, Xuemei; Roller, Anna; Carter, Kathleen; Paul, Ian; Bhatt, Abhay J.; Lin, Rick C. S.; Fan, Lir-Wan

    2016-01-01

    Perinatal infection is a well-identified risk factor for a number of neurodevelopmental disorders, including brain white matter injury (WMI) and Autism Spectrum Disorders (ASD). The underlying mechanisms by which early life inflammatory events cause aberrant neural, cytoarchitectural, and network organization, remain elusive. This study is aimed to investigate how systemic lipopolysaccharide (LPS)-induced neuroinflammation affects microglia phenotypes and early neural developmental events in rats. We show here that LPS exposure at early postnatal day 3 leads to a robust microglia activation which is characterized with mixed microglial proinflammatory (M1) and anti-inflammatory (M2) phenotypes. More specifically, we found that microglial M1 markers iNOS and MHC-II were induced at relatively low levels in a regionally restricted manner, whereas M2 markers CD206 and TGFβ were strongly upregulated in a sub-set of activated microglia in multiple white and gray matter structures. This unique microglial response was associated with a marked decrease in naturally occurring apoptosis, but an increase in cell proliferation in the subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus. LPS exposure also leads to a significant increase in oligodendrocyte lineage population without causing discernible hypermyelination. Moreover, LPS-exposed rats exhibited significant impairments in communicative and cognitive functions. These findings suggest a possible role of M2-like microglial activation in abnormal neural development that may underlie ASD-like behavioral impairments. PMID:27723799

  19. Prenatal and postnatal neuromuscular development of the ureterovesical junction.

    PubMed

    Pirker, Martina E; Rolle, Udo; Shinkai, Toko; Shinkai, Masato; Puri, Prem

    2007-04-01

    The mechanisms underlying functional maturation of the ureterovesical junction during infancy are still not fully understood. We analyzed the development of smooth muscle components of the ureterovesical junction and their nerve supply in the fetal, newborn and adolescent pig. Bladder specimens were obtained from porcine fetuses at gestational ages 60 days (5) and 90 days (5), newborn piglets (5) and 6-month-old pigs (4). Serial sections of the ureterovesical junction were investigated by Masson's trichrome, and hematoxylin and eosin histological staining, enzyme immunohistochemistry for alpha-smooth muscle actin and desmin, as well as double immunofluorescence staining using the neuronal marker peripherin and smooth muscle actin. At day 60 the detrusor muscle already consisted of distinctive muscle bundles with rich innervation, while the smooth muscle coat of the extravesical ureter and subsequently the intravesical ureter had only started to differentiate. At day 60 innervation of the extravesical ureteral smooth muscle was well developed, while the innervation of the intramural part did not mature until birth. Muscle fibers of the periureteral sheath were well distinguishable at day 60 but innervation of these fibers was sparse during fetal life and showed a remarkable increase during the postnatal period. All smooth muscle components showed a striking increase in muscle bulk between the neonatal and adolescent stages. Our findings show that the smooth muscle components and innervation of the ureterovesical junction continue to mature during the postnatal period. This may have implications for managing ureterovesical junction disorders.

  20. Major epigenetic development distinguishing neuronal and non-neuronal cells occurs postnatally in the murine hypothalamus

    PubMed Central

    Li, Ge; Zhang, Wenjuan; Baker, Maria S.; Laritsky, Eleonora; Mattan-Hung, Natalia; Yu, Dahai; Kunde-Ramamoorthy, Govindarajan; Simerly, Richard B.; Chen, Rui; Shen, Lanlan; Waterland, Robert A.

    2014-01-01

    Prenatal and early postnatal environment can persistently alter one's risk of obesity. Environmental effects on hypothalamic developmental epigenetics constitute a likely mechanism underlying such ‘developmental programming’ of energy balance regulation. To advance our understanding of these processes, it is essential to develop approaches to disentangle the cellular and regional heterogeneity of hypothalamic developmental epigenetics. We therefore performed genome-scale DNA methylation profiling in hypothalamic neurons and non-neuronal cells at postnatal day 0 (P0) and P21 and found, surprisingly, that most of the DNA methylation differences distinguishing these two cell types are established postnatally. In particular, neuron-specific increases in DNA methylation occurred extensively at genes involved in neuronal development. Quantitative bisulfite pyrosequencing verified our methylation profiling results in all 15 regions examined, and expression differences were associated with DNA methylation at several genes. We also identified extensive methylation differences between the arcuate (ARH) and paraventricular nucleus of the hypothalamus (PVH). Integrating these two data sets showed that genomic regions with PVH versus ARH differential methylation strongly overlap with those undergoing neuron-specific increases from P0 to P21, suggesting that these developmental changes occur preferentially in either the ARH or PVH. In particular, neuron-specific methylation increases at the 3′ end of Shh localized to the ARH and were positively associated with gene expression. Our data indicate a key role for DNA methylation in establishing the gene expression potential of diverse hypothalamic cell types, and provide the novel insight that early postnatal life is a critical period for cell type-specific epigenetic development in the murine hypothalamus. PMID:24186871

  1. [Current Practice of Pre- and Postnatal Screening and Future Developments for Evidence Based Guidelines].

    PubMed

    Hebebrand, J; Hamelmann, E; Hartmann, A; Holtmann, M; Jöckel, K-H; Kremer, U; Legenbauer, T; Lücke, T; Radkowski, K; Reinehr, T; Wand, K; Mühlig, Y; Föcker, M

    2017-01-01

    Objectives: In this selective review we provide an overview of the current pre- and postnatal screenings up to 18 years established in Germany to inform physicians of different medical fields (gynecologists, pediatricians, general practitioners, other medical specialists who treat children, adolescents or pregnant females). Current State: Research on screening for different types of cancer has frequently failed to show any benefit. Thus, there is a need to broaden the evidence basis related to medical screenings especially for children and adolescents. Outlook: Potential future developments of pre- and postnatal screenings are illustrated including their social impact. The lack of an early detection of mental health problems is pointed out. An interdisciplinary collaboration and research is required to accumulate evidence with regard to medical screenings and to consider health economic and ethical aspects. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Postnatal morphine administration alters hippocampal development in rats.

    PubMed

    Traudt, Christopher M; Tkac, Ivan; Ennis, Kathleen M; Sutton, Leah M; Mammel, Daniel M; Rao, Raghavendra

    2012-01-01

    Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have an altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo (1)H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ-aminobutyric acid (GABA), taurine, and myo-insotol were decreased, whereas concentrations of glutathione, phosphoethanolamine, and choline-containing compounds were increased in morphine-exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60-70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure.

  3. Postnatal Morphine Administration Alters Hippocampal Development in Rats

    PubMed Central

    Traudt, Christopher M.; Tkac, Ivan; Ennis, Kathleen M.; Sutton, Leah M.; Mammel, Daniel M.; Rao, Raghavendra

    2011-01-01

    Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg of morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo 1H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ-aminobutyric acid (GABA), taurine and myo-insotol were decreased, while glutathione, phosphoethanolamine and choline-containing compounds concentrations were increased in morphine-exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60-70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure. PMID:21971612

  4. Gestational and postnatal protein deficiency affects postnatal development and histomorphometry of liver, kidneys, and ovaries of female rats' offspring.

    PubMed

    Almeida, Fernanda R C L; Silva, Gerluza A B; Fiúza, Aparecida T L; Chianca, Deoclécio A; Ferreira, Anderson J; Chiarini-Garcia, Hélio

    2012-04-01

    Pre- and postnatal protein deficiency may lead to decreased foetal intra-uterine development and postnatal growth, which is common in developing countries. The present study aimed to investigate the consequences of a low-protein intake during gestation and postnatally on adult female rats' offspring. Female rats were given either a control or a protein-deficient diet throughout the gestation and lactation periods. A subset of females was killed at day 20 of pregnancy for foetal and placental measurements. Another subset of females farrowed and the number, length, and weight of the offspring were measured. After weaning, the offspring received the same diet as their dams until 70 days of age. They were sacrificed, and some organs were weighed and collected for histomorphometrical analyses. Placental weight and size and foetal weight were lower in protein-deficient dams. The weight and length of pups at birth were also lower in the deficient group. The organs to body weight ratio were higher in the deficient animals at 70 days of age. The protein-deficient female offspring had a smaller ovarian area, greater numbers of primordial follicles and developing follicles per square millimetres of ovarian cortex, and no corpora lutea. The liver showed smaller nuclear diameter of the hepatocytes and height of the hepatocytes cords. The kidneys showed smaller cortical area with reduced glomerular number and diameter. These results provide the first evidence of the histomorphological changes of the association between gestational and postnatal protein deficiency in female rats' offspring.

  5. Malformations of Cortical Development: From Postnatal to Fetal Imaging.

    PubMed

    Lerman-Sagie, Tally; Leibovitz, Zvi

    2016-09-01

    Abnormal fetal corticogenesis results in malformations of cortical development (MCD). Abnormal cell proliferation leads to microcephaly or megalencephaly, incomplete neuronal migration results in heterotopia and lissencephaly, neuronal overmigration manifests as cobblestone malformations, and anomalous postmigrational cortical organization is responsible for polymicrogyria and focal cortical dysplasias. MCD comprises various congenital brain disorders, caused by different genetic, infectious, or vascular etiologies and is associated with significant neurological morbidity. Although MCD are rarely diagnosed prenatally, both dedicated multiplanar neurosonography and magnetic resonance imaging enable good demonstration of fetal cortical development. The imaging signs of fetal MCD are: delayed or absent cerebral sulcation; premature abnormal sulci; thin and irregular hemispheric parenchyma; wide abnormal overdeveloped gyri; wide opening of isolated sulci; nodular bulging into the lateral ventricles; cortical clefts; intraparenchymal echogenic nodules; and cortical thickening. The postnatal and prenatal imaging features of four main malformations of cortical development-lissencephaly, cobblestone malformations, periventricular nodular heterotopia, and polymicrogyria-are described.

  6. Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

    PubMed

    Meaney, Michael J; Aitken, David H; Bodnoff, Shari R; Iny, Linda J; Tatarewicz, Joseph E; Sapolsky, Robert M

    2013-10-01

    Norway rat pups were either handled (H) or undisturbed (nonhandled, NH) in the period between birth and weaning on Day 21. Following weaning, half of the animals in each group were housed socially (Soc), and half were housed in isolation (Isol). At 120-150 days of age, all animals were sacrificed, and the following regions were dissected and frozen at -70 °C until the time of assay: frontal cortex, hippocampus, hypothalamus, amygdala, septum, and pituitary. [3H]Dexamethasone (3H Dex) binding in each region was examined by an in vitro, cytosol, receptor assay. 3H Dex binding was significantly higher in the hippocampus of both H-Soc and H-Isol than in NH groups. In the frontal cortex, 3H Dex binding was higher in the H-Soc animals than in the H-Isol and NH-Isol animals. There were no significant handling or housing effects found in the amygdala, hypothalamus, septum, or pituitary. Thus, early postnatal handling appears to influence the development of the glucocorticoid receptor system in the hippocampus and frontal cortex. These results are discussed as providing a possible mechanism for some of the previously reported effects of early handling on the development of the pituitary-adrenal response to stress. 2013 APA, all rights reserved

  7. Early postnatal deprivation of active sleep with desipramine or zimeldine impairs later behavioural reactivity to auditory stimuli in rats.

    PubMed

    Hilakivi, L A; Taira, T; Hilakivi, I

    1988-02-01

    To examine the functional significance of early postnatal active sleep for the development of behavioural reactivity to auditory stimuli, rat pups were daily injected i.p. from the 7th to the 18th postnatal days with 5 mg kg-1 (6.6 mmol l-1) desipramine or 25 mg kg-1 (12.2 mmol l-1) zimeldine. Sleep-wake behaviour was recorded with a static-charge-sensitive bed (SCSB) method. Both desipramine and zimeldine suppressed the percentage of active sleep relative to the total recording time throughout the treatment period. In addition, these drugs increased the percentage of quiet state and waking. At the age of 38 days the zimeldine-treated rats showed more motor activity in the open field than the controls. At the age of 39 and 78 days all rat groups behaved similarly in the open field. Startle measures and motor activation, provoked by auditory stimulation, were determined by the SCSB method when the rats were 4 months of age. Auditory stimuli, consisting of a series of ten clicks, induced a greater number of startles as well as strong movement responses in the control rats than in the desipramine- or zimeldine-treated rats. The number of small movement responses did not differ between the rat groups. These findings indicate that early postnatal active sleep and the monoaminergic systems regulating it may be important for the normal development of neuronal circuitry associated with later reactivity to auditory stimuli.

  8. Evaluation of gene expression profiles and pathways underlying postnatal development in mouse sclera

    PubMed Central

    Lim, Wan’E.; Kwan, Jia Lin; Goh, Liang Kee; Beuerman, Roger W.

    2012-01-01

    Purpose The aim of this study was to identify the genes and pathways underlying the growth of the mouse sclera during postnatal development. Methods Total RNA was isolated from each of 30 single mouse sclera (n=30, 6 sclera each from 1-, 2-, 3-, 6-, and 8-week-old mice) and reverse-transcribed into cDNA using a T7-N6 primer. The resulting cDNA was fragmented, labeled with biotin, and hybridized to a Mouse Gene 1.0 ST Array. ANOVA analysis was then performed using Partek Genomic Suite 6.5 beta and differentially expressed transcript clusters were filtered based on a selection criterion of ≥2 relative fold change at a false discovery rate of ≤5%. Genes identified as involved in the main biologic processes during postnatal scleral development were further confirmed using qPCR. A possible pathway that contributes to the postnatal development of the sclera was investigated using Ingenuity Pathway Analysis software. Results The hierarchical clustering of all time points showed that they did not cluster according to age. The highest number of differentially expressed transcript clusters was found when week 1 and week 2 old scleral tissues were compared. The peroxisome proliferator- activated receptor gamma coactivator 1-alpha (Ppargc1a) gene was found to be involved in the networks generated using Ingenuity Pathway Studio (IPA) from the differentially expressed transcript cluster lists of week 2 versus 1, week 3 versus 2, week 6 versus 3, and week 8 versus 6. The gene expression of Ppargc1a varied during scleral growth from week 1 to 2, week 2 to 3, week 3 to 6, and week 6 to 8 and was found to interact with a different set of genes at different scleral growth stages. Therefore, this indicated that Ppargc1a might play a role in scleral growth during postnatal weeks 1 to 8. Conclusions Gene expression of eye diseases should be studied as early as postnatal weeks 1–2 to ensure that any changes in gene expression pattern during disease development are detected. In

  9. Evaluation of gene expression profiles and pathways underlying postnatal development in mouse sclera.

    PubMed

    Lim, Wan'E; Kwan, Jia Lin; Goh, Liang Kee; Beuerman, Roger W; Barathi, Veluchamy A

    2012-01-01

    The aim of this study was to identify the genes and pathways underlying the growth of the mouse sclera during postnatal development. Total RNA was isolated from each of 30 single mouse sclera (n=30, 6 sclera each from 1-, 2-, 3-, 6-, and 8-week-old mice) and reverse-transcribed into cDNA using a T7-N(6) primer. The resulting cDNA was fragmented, labeled with biotin, and hybridized to a Mouse Gene 1.0 ST Array. ANOVA analysis was then performed using Partek Genomic Suite 6.5 beta and differentially expressed transcript clusters were filtered based on a selection criterion of ≥ 2 relative fold change at a false discovery rate of ≤ 5%. Genes identified as involved in the main biologic processes during postnatal scleral development were further confirmed using qPCR. A possible pathway that contributes to the postnatal development of the sclera was investigated using Ingenuity Pathway Analysis software. The hierarchical clustering of all time points showed that they did not cluster according to age. The highest number of differentially expressed transcript clusters was found when week 1 and week 2 old scleral tissues were compared. The peroxisome proliferator- activated receptor gamma coactivator 1-alpha (Ppargc1a) gene was found to be involved in the networks generated using Ingenuity Pathway Studio (IPA) from the differentially expressed transcript cluster lists of week 2 versus 1, week 3 versus 2, week 6 versus 3, and week 8 versus 6. The gene expression of Ppargc1a varied during scleral growth from week 1 to 2, week 2 to 3, week 3 to 6, and week 6 to 8 and was found to interact with a different set of genes at different scleral growth stages. Therefore, this indicated that Ppargc1a might play a role in scleral growth during postnatal weeks 1 to 8. Gene expression of eye diseases should be studied as early as postnatal weeks 1-2 to ensure that any changes in gene expression pattern during disease development are detected. In addition, we propose that Ppargc1a

  10. Increased postnatal inflammation in mechanically ventilated preterm infants born to mothers with early-onset preeclampsia.

    PubMed

    Turunen, Riikka; Andersson, Sture; Laivuori, Hannele; Kajantie, Eero; Siitonen, Sanna; Repo, Heikki; Nupponen, Irmeli

    2011-01-01

    Preeclampsia and preterm labor often underlie preterm birth, and are associated with maternal inflammation. In preterm infants, respiratory distress syndrome (RDS) and mechanical ventilation are associated with systemic inflammation. We aimed to study whether early-onset preeclampsia or preterm labor modulate the systemic inflammation affecting preterm infants with RDS. We recruited mechanically ventilated infants with gestational ages <32 weeks; 11 infants were born after early-onset preeclampsia and 25 after preterm labor. Blood was drawn during postnatal days 1-7, and the mean values of days 1-2, 3-4 and 5-6 were used. Phagocyte CD11b expression was analyzed with flow cytometry, and plasma C-reactive protein (CRP) concentrations with immunoturbidimetry. As compared with infants born after preterm labor, infants born after early-onset preeclampsia had higher CD11b expression on days 1-6 on both neutrophils and monocytes. In addition, infants born after early-onset preeclampsia had higher CRP concentrations on days 2-6 (all p < 0.05). As compared with infants born after preterm labor to mothers without preeclampsia, infants born after early-onset preeclampsia presented with a stronger postnatal systemic inflammatory reaction. Antenatal exposure to preeclampsia may induce fetal leukocyte priming and regulation of inflammation, and thereby modify postnatal inflammatory reactions and morbidity. Copyright © 2011 S. Karger AG, Basel.

  11. Early postnatal proteolipid promoter-expressing progenitors produce multilineage cells in vivo.

    PubMed

    Guo, Fuzheng; Ma, Joyce; McCauley, Erica; Bannerman, Peter; Pleasure, David

    2009-06-03

    Proteolipid promoter (plp promoter) activity in the newborn mouse CNS is restricted to NG2-expressing oligodendroglial progenitor cells and oligodendrocytes. There are two populations of NG2 progenitors based on their plp promoter expression. Whereas the general population of NG2 progenitors has been shown to be multipotent in vitro and after transplantation, it is not known whether the subpopulation of plp promoter-expressing NG2 progenitors [i.e., plp promoter-expressing NG2 progenitors (PPEPs)] has the potential to generate multilineage cells during normal development in vivo. We addressed this issue by fate mapping Plp-Cre-ER(T2)/Rosa26-EYFP (PCE/R) double-transgenic mice, which carried an inducible Cre gene under the control of the plp promoter. Expression of the enhanced yellow fluorescent protein (EYFP) reporter gene in PPEPs was elicited by administering tamoxifen to postnatal day 7 PCE/R mice. We have demonstrated that early postnatal PPEPs, which had been thought to be restricted to the oligodendroglial lineage, also unexpectedly gave rise to a subset of immature, postmitotic, protoplasmic astrocytes in the gray matter of the spinal cord and ventral forebrain, but not in white matter. Furthermore, these PPEPs also gave rise to small numbers of immature, DCX (doublecortin)-negative neurons in the ventral forebrain, dorsal cerebral cortex, and hippocampus. EYFP-labeled representatives of each of these lineages survived to adulthood. These findings indicate that there are regional differences in the fates of neonatal PPEPs, which are multipotent in vivo, giving rise to oligodendrocytes, astrocytes, and neurons.

  12. Erythropoietin and respiratory control at adulthood and during early postnatal life.

    PubMed

    Soliz, Jorge

    2013-01-01

    Erythropoietin (Epo) was originally discovered as a cytokine able to increase the production of red blood cells upon conditions of reduced oxygen availability. Now we know that Epo does far more than "only" augmenting the number of erythrocytes. Since the demonstration that Epo (and its receptor) is expressed in the mammalian brain, several elegant experiments were performed to reveal the function of this molecule in the neuronal tissue. Accordingly to its anti-apoptotic, neurotrophic and proliferative effects in the bone marrow, it was suitably suggested that upon pathological conditions Epo exerts neuroprotective functions (i.e. reducing the infarct volume of stroke, thus allowing better and faster recovery). We considered however, that Epo in brain might also exert a physiological function. Indeed, we found that Epo is an important modulator of the respiratory control system. By using adult mice we showed that Epo increases the hypoxic ventilatory response by interacting with both the central respiratory network (brainstem) as well as the main peripheral sensory organs detecting systemic hypoxia, the carotid bodies. More recently, our research turned to examine the exciting hypothesis that Epo is also implicated in the regulation of the neuronal control of ventilation during the postnatal development. The objective of this review is to summarize the role and mode of action of Epo on respiratory control in adult mammals and highlight the potential pathways by which this cytokine achieve this function. Additionally, we review recent evidences showing that Epo play a crucial role in setting the respiratory motor output (measured on the isolated brainstem spinal cord preparation, en bloc technique) during the early postnatal life.

  13. Recruitment of early postnatal parvalbumin-positive hippocampal interneurons by GABAergic excitation.

    PubMed

    Sauer, Jonas-Frederic; Bartos, Marlene

    2010-01-06

    GABAergic synaptic inputs targeting cortical principal cells undergo marked changes in their functional properties from depolarizing at early postnatal life to hyperpolarizing at mature stages. In contrast, the nature of GABA(A) receptor-mediated signaling in interneurons during maturation of neuronal networks is controversial. By using gramicidin perforated-patch and whole-cell recordings from LIM homeobox 6 (Lhx6)-positive dentate gyrus perisomatic-targeting parvalbumin-expressing interneurons (PV-INs), we show that signaling at first formed GABAergic synapses at postnatal day 3 (P3) is excitatory and switches to shunting during the course of the first to second postnatal week. GABAergic synaptic inputs at P3-P6 reliably evoke action potentials in 65% of Lhx6-EGFP-expressing perisomatic-targeting cells and boost spike induction upon conjoint activation of glutamatergic fibers. Thus, GABAergic inputs change their functional role during maturation. They facilitate the recruitment of perisomatic-targeting INs in early postnatal circuits when network connectivity and synaptic glutamate receptor-mediated excitation are low and control spike timing at later stages when connectivity and glutamate-mediated drive are high.

  14. Profiling analysis of long non-coding RNAs in early postnatal mouse hearts

    PubMed Central

    Sun, Xiongshan; Han, Qi; Luo, Hongqin; Pan, Xiaodong; Ji, Yan; Yang, Yao; Chen, Hanying; Wang, Fangjie; Lai, Wenjing; Guan, Xiao; Zhang, Qi; Tang, Yuan; Chu, Jianhong; Yu, Jianhua; Shou, Weinian; Deng, Youcai; Li, Xiaohui

    2017-01-01

    Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition. PMID:28266538

  15. The effect of early postnatal discharge from hospital for women and infants: a systematic review protocol.

    PubMed

    Jones, Eleanor; Taylor, Beck; MacArthur, Christine; Pritchett, Ruth; Cummins, Carole

    2016-02-08

    The length of postnatal hospital stay has declined over the last 40 years. There is little evidence to support a policy of early discharge following birth, and there is some concern about whether early discharge of mothers and babies is safe. The Cochrane review on the effects of early discharge from hospital only included randomised controlled trials (RCTs) which are problematic in this area, and a systematic review including other study designs is required. The aim of this broader systematic review is to determine possible effects of a policy of early postnatal discharge on important maternal and infant health-related outcomes. A systematic search of published literature will be conducted for randomised controlled trials, non-randomised controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series studies (ITS) that report on the effect of a policy of early postnatal discharge from hospital. Databases including Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and Science Citation Index will be searched for relevant material. Reference lists of articles will also be searched in addition to searches to identify grey literature. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria for risk of bias tool. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analysis using a random effects model will be used to combine data. Where significant heterogeneity is present, data will be combined in a narrative synthesis. The findings will be reported according to the preferred reporting items for systematic reviews (PRISMA) statement. Information on the effects of early postnatal discharge from hospital will be important for policy makers and clinicians providing maternity care. This review will also identify any gaps in the current

  16. Early postnatal stress alters the extinction of context-dependent conditioned fear in adult rats.

    PubMed

    Matsumoto, Machiko; Togashi, Hiroko; Konno, Kohtaro; Koseki, Hiroyo; Hirata, Riki; Izumi, Takeshi; Yamaguchi, Taku; Yoshioka, Mitsuhiro

    2008-05-01

    Fear extinction is hypothesized to be a learning process based on a new inhibitory memory. The present study was conducted to elucidate the effect of early postnatal stress on the extinction of context-dependent fear memory in adult rats, with a focus on the serotonergic system. Extinction was estimated by the expression of freezing behavior during repeated extinction trials (i.e., repeated exposure to contextual fear conditioning) on consecutive days. The decrease in fear expression was attenuated in adult rats that had been subjected to footshock (FS) at the third postnatal week (3wFS), but not in those exposed to footshock at the second postnatal week (2wFS). The decreased attenuation of freezing behavior observed in 3wFS was abolished by repeated treatment with the partial N-methyl-D-aspartate receptor agonist D-cycloserine (15 mg/kg, i.p., for 4 days), which has been shown to facilitate cue-dependent extinction. Repeated treatment with the serotonin 5-hydroxytryptamine-1A (5-HT(1A)) receptor agonist tandospirone (1 mg/kg, i.p., for 4 days) prevented the expression of freezing behavior in 3wFS, whereas diazepam treatment (1 mg/kg, i.p., for 4 days) in 3wFS did not. These results suggest that exposure to early postnatal stress at the third week is responsible for attenuating extinction of contextual fear conditioning and is mediated by a serotonergic 5-HT(1A) receptor mechanism. In other words, exposure to traumatic events during the early postnatal period might precipitate long-lasting alterations in synaptic function that underlie extinction processes of context-dependent fear memory.

  17. Apoptosis Process in Mouse Leydig Cells during Postnatal Development

    NASA Astrophysics Data System (ADS)

    Salles Faria, Maria José; Simões, Zilá Paulino; Luz; Orive Lunardi, Laurelucia; Hartfelder, Klaus

    2003-02-01

    The development of Leydig cells in mammals has been widely described as a biphasic pattern with two temporally mature Leydig cell populations, fetal stage followed by the adult generation beginning at puberty. In the present study, mouse Leydig cells were examined for apoptosis during postnatal testis development using electron microscopy and in situ DNA fragmentation by terminal deoxynucleotidyl transferase staining (TdT). Both the morphological study and the DNA fragmentation analysis showed that cellular death by apoptosis did not occur in Leydig cells during the neonatal, prepubertal, puberty, and adult periods. From these results, we suggest that the remaining fetal Leydig cells in the neonatal testis are associated with the involution or degeneration processes. In contrast, in the prepubertal and puberty stages, fragmentation of apoptotic DNA was detected in germ cells present in some seminiferous tubules.

  18. Morphological properties of mouse retinal ganglion cells during postnatal development.

    PubMed

    Coombs, Julie L; Van Der List, Deborah; Chalupa, Leo M

    2007-08-20

    Quantitative methods were used to assess dendritic stratification and other structural features of developing mouse retinal ganglion cells from birth to after eye opening. Cells were labeled by transgenic expression of yellow fluorescent protein, DiOlistics or diffusion of DiI, and subsequently imaged in three dimensions on a confocal microscope followed by morphometric analysis of 13 different structural properties. At postnatal day 1 (P1), the dendrites of all cells ramified across the vertical extent of the inner plexiform layer (IPL). By P3/4, dendrites were largely confined to different strata of the IPL. The stratification of dendrites initially reflected a retraction of widely ramifying dendritic processes, but for the most part this was due to the subsequent vertical expansion of the IPL. By P8, distinct cell classes could be recognized, although these had not yet attained adult-like properties. The structural features differentiating cell classes were found to follow three different developmental trends. The mean values of one set of morphological parameters were essentially unchanged throughout postnatal development; another set of measures showed a rapid rise with age to adult values; and a third set of measures first increased with age and later decreased, with the regressive events initiated around the time of eye opening. These findings suggest that the morphological development of retinal ganglion cells is regulated by diverse factors operating during different but overlapping time periods. Our results also suggest that dendritic stratification may be more highly specified in the developing mammalian retina than has been previously realized.

  19. Behavioral and cognitive changes after early postnatal lesions of the rat mediodorsal thalamus.

    PubMed

    Ouhaz, Zakaria; Ba-M'hamed, Saadia; Mitchell, Anna S; Elidrissi, Abdeslem; Bennis, Mohamed

    2015-10-01

    Early insults to the thalamus result in functional and/or structural abnormalities in the cerebral cortex. However, differences in behavioral and cognitive changes after early insult are not well characterized. The present study assessed whether early postnatal damage to mediodorsal nucleus of the thalamus (MD), reciprocally interconnected with the prefrontal cortex, causes behavioral and cognitive alterations in young adult rats. Rat pups at postnatal day 4 received bilateral electrolytic lesion of MD, or a MD Sham lesion or were anesthetized controls; on recovery they were returned to their mothers until weaning. Seven weeks later, all rats were tested with the following behavioral and cognitive paradigms: T-maze test, open field test, actimetry, elevated plus maze test, social interactions test and passive avoidance test. Rats with bilateral MD damage presented with disrupted recognition memory, deficits in shifting response rules, significant hypoactivity, increased anxiety-like behavior, deficits in learning associations as well as decreased locomotor activity, and reduced social interactions compared to MD Sham lesion and anesthetized Control rats. The lesion also caused significant decreases in pyramidal cell density in three frontal cortex regions: medial infralimbic cortex, dorsolateral anterior cortex, and cingulate Cg1 cortex. The present findings suggest a functional role for MD in the postnatal maturation of affective behavior. Further some of the behavioral and cognitive alterations observed in these young adult rats after early MD lesion are reminiscent of those present in major psycho-affective disorders, such as schizophrenia in humans.

  20. Adult Neuropsychological Performance Following Prenatal and Early Postnatal Exposure to Tetrachloroethylene (PCE)-contaminated Drinking Water

    PubMed Central

    Janulewicz, Patricia A; White, Roberta F; Martin, Brett M; Winter, Michael R; Weinberg, Janice M; Vieira, Veronica; Aschengrau, Ann

    2012-01-01

    This population-based retrospective cohort study examined adult performance on a battery of neuropsychological tests in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Results of crude and multivariate analyses among 35 exposed and 28 unexposed subjects showed no association between prenatal and early postnatal exposure and decrements on tests that assess abilities in the domains of omnibus intelligence, academic achievement or language. The results were suggestive of an association between prenatal and early postnatal PCE exposure and diminished performance on tests that assessed abilities in the domains of visuospatial functioning, learning and memory, motor, attention and mood. Because the sample size was small, most findings were not statistically significant. Future studies with larger sample sizes should be conducted to further define the neuropsychological consequences of early developmental PCE exposure. PMID:22522125

  1. Developmental Injury to the Cerebellar Cortex Following Hydroxyurea Treatment in Early Postnatal Life: An Immunohistochemical and Electron Microscopic Study.

    PubMed

    Martí, Joaquín; Molina, Vanesa; Santa-Cruz, M C; Hervás, José P

    2017-02-01

    Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.

  2. Ontogeny, postnatal development and ageing of endocrine pancreas in Bubalus bubalis

    PubMed Central

    LUCINI, C.; CASTALDO, L.; LAI, O.; DE VICO, G.

    1998-01-01

    The ontogenesis, postnatal development and ageing of the endocrine pancreas in mammals have not been extensively studied. In order to improve understanding of this organ, we studied the buffalo pancreas during fetal and postnatal development. Glucagon, insulin and somatostatin immunoreactive cells (i.c.) were first seen in 2-mo-old embryos. Pancreatic polypeptide (PP) i.c. were observed during the 3rd month of gestation. The early embryo pancreas was almost totally composed of endocrine tissue. The endocrine portion only slightly increased in mass with animal growth, whereas the exocrine portion noticeably increased in mass during the late fetal and postnatal periods. In adults, therefore, the exocrine portion was more evident than the endocrine portion. Three types of islet were observed in fetal and young buffalos: small, large and PP-islets. The small islets were composed of insulin, glucagon, somatostatin and PP i.c. The large islets were primarily composed of insulin i.c. and a few glucagon, somatostatin and PP i.c. The PP islets were mostly composed of PP i.c. with a few somatostatin, insulin and glucagon i.c. The number of large islets greatly diminished by adulthood. Glucagon, insulin, somatostatin and PP i.c. were also seen scattered in the exocrine parenchyma and along the duct epithelium. In the duct epithelium, these cells were either single or grouped, and they sometimes formed a protrusion projecting towards the connective tissue. These morphological features were primarily observed in fetuses and young buffalos. PMID:9688507

  3. Homeostasis of neuronal avalanches during postnatal cortex development in vitro

    PubMed Central

    Stewart, Craig V.; Plenz, Dietmar

    2009-01-01

    Cortical networks in vivo and in vitro are spontaneously active in the absence of inputs, generating highly variable bursts of neuronal activity separated by up to seconds of quiescence. Previous measurements in adult rat cortex revealed an intriguing underlying organization of these dynamics, termed neuronal avalanches, which is indicative of a critical network state. Here we demonstrate that neuronal avalanches persist throughout development in cortical slice cultures from newborn rats. More specifically, we find that in spite of large variations of average rate in activity, spontaneous bursts occur with power-law distributed sizes (exponent -1.5) and a critical branching parameter close to 1. Our findings suggest that cortical networks homeostatically regulate a critical state during postnatal maturation. PMID:18082894

  4. Postnatal development of plasma amino acids in hyperphagic rats.

    PubMed

    Salvadó, M J; Segués, T; Arola, L

    1991-01-01

    The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30.

  5. The Yugoslavia Prospective Lead Study: contributions of prenatal and postnatal lead exposure to early intelligence.

    PubMed

    Wasserman, G A; Liu, X; Popovac, D; Factor-Litvak, P; Kline, J; Waternaux, C; LoIacono, N; Graziano, J H

    2000-01-01

    To investigate associations between the timing of lead (Pb) exposure on early intelligence, we examined the results of psychometric evaluations at ages 3, 4, 5, and 7 years, from 442 children whose mothers were recruited during pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia. We compared the relative contribution of prenatal blood lead (BPb) with that of relative increases in BPb in either the early (0-2 years) or the later (from 2 years on) postnatal period to child intelligence measured longitudinally at ages 3 and 4 (McCarthy GCI), 5 (Wechsler Preschool and Primary Scale of Intelligence-Revised, WPPSI-R IQ), and 7 (Wechsler Intelligence Scale for Children-version III, WISC-III IQ), controlling for: Home Observation for Measurement of the Environment (HOME) quality; maternal age, intelligence, education, and ethnicity; and birthweight and gender. Elevations in both prenatal and postnatal BPb were associated with small decrements in young children's intelligence.

  6. Major epigenetic development distinguishing neuronal and non-neuronal cells occurs postnatally in the murine hypothalamus

    USDA-ARS?s Scientific Manuscript database

    Prenatal and early postnatal environment can persistently alter one's risk of obesity. Environmental effects on hypothalamic developmental epigenetics constitute a likely mechanism underlying such 'developmental programming' of energy balance regulation. To advance our understanding of these process...

  7. Detrimental effects of tobacco smoke exposure during development on postnatal lung function and asthma.

    PubMed

    Wang, Lei; Pinkerton, Kent E

    2008-03-01

    Exposure to environmental tobacco smoke (ETS) during fetal development and early postnatal life is perhaps the most ubiquitous and hazardous of children's environmental exposures. The developing lung is highly susceptible to ETS. A large body of literature links both prenatal maternal smoking and children's ETS exposure to decreased lung growth. This review summarizes the state of the knowledge, including both human epidemiology and laboratory animal experiments, linking ETS, lung development, and respiratory outcomes. Important issues discussed include lung development and lung function and asthma in relation to ETS exposure during critical windows of growth. Prenatal exposure to ETS is associated with impaired lung function and increased risk of developing asthma, whereas postnatal exposure mainly acts to trigger respiratory symptoms and asthma attacks, but it also plays an important role in the occurrence of asthma in children. This review provides evidence that avoidance of ETS exposure both before and after birth is beneficial to long-term respiratory health, because airway function in later life is believed to be largely determined by lung development occurring in utero and in early infancy.

  8. EARLY POSTNATAL OVERNUTRITION: POTENTIAL ROLES OF GASTROINTESTINAL VAGAL AFFERENTS AND BRAIN-DERIVED NEUROTROPHIC FACTOR

    PubMed Central

    Fox, Edward A.; Biddinger, Jessica E.

    2012-01-01

    Abnormal perinatal nutrition (APN) results in a predisposition to develop obesity and the metabolic syndrome and thus may contribute to the prevalence of these disorders. Obesity, including that which develops in organisms exposed to APN, has been associated with increased meal size. Vagal afferents of the gastrointestinal (GI) tract contribute to regulation of meal size by transmitting satiation signals from gut-to-brain. Consequently, APN could increase meal size by altering this signaling, possibly through changes in expression of factors that control vagal afferent development or function. Here two studies that addressed these possibilities are reviewed. First, meal patterns, meal microstructure, and the structure and density of vagal afferents that innervate the intestine were examined in mice that experienced early postnatal overnutrition (EPO). These studies provided little evidence for EPO effects on vagal afferents as it did not alter meal size or vagal afferent density or structure. However, these mice exhibited modest hyperphagia due to a satiety deficit. In parallel, the possibility that brain-derived neurotrophic factor (BDNF) could mediate APN effects on vagal afferent development was investigated. Brain-derived neurotrophic factor was a strong candidate because APN alters BDNF levels in some tissues and BDNF knockout disrupts development of vagal sensory innervation of the GI tract. Surprisingly, smooth muscle-specific BDNF knockout resulted in early-onset obesity and hyperphagia due to increases in meal size and frequency. Microstructure analysis revealed decreased decay of intake rate during a meal in knockouts, suggesting loss of vagal negative feedback contributed to their increase in meal size. However, meal-induced c-Fos activation within the dorsal vagal complex suggested this effect could be due to augmentation of vago-vagal reflexes. A model is proposed to explain how high-fat diet consumption produces increased obesity in organisms exposed

  9. Perinatal steroid exposure and respiratory control during early postnatal life.

    PubMed

    Soliz, J; Joseph, V

    2005-11-15

    Numerous factors involved in general homeostasis are able to modulate respiratory motor output. These include placental-derived steroids, which are necessary for maternal physiological adjustments during gestation, including respiratory stimulation. Despite the fact that these hormones exert potent effects on neural development in the fetus, the hypothesis of a developmental control of the neural respiratory network by placental-derived steroids has been approached experimentally only recently. The objective of this review is to summarize the role and mode of action of placental steroids on respiratory control in adult mammals and highlight the potential pathways by which such steroids are supplied to the developing fetus. Additionally, we present recent results showing that the beta estradiol and progesterone receptors are expressed in the carotid body of newborn male rats, thus supporting the hypothesis of receptor-mediated effect of estradiol and progesterone on carotid bodies.

  10. Postnatal development of myenteric neurochemical phenotype and impact on neuromuscular transmission in the rat colon.

    PubMed

    de Vries, P; Soret, R; Suply, E; Heloury, Y; Neunlist, M

    2010-08-01

    Profound changes in intestinal motility occur during the postnatal period, but the involvement of the enteric nervous system (ENS), a key regulator of gastrointestinal (GI) motility, in these modifications remains largely unknown. We therefore investigated the postnatal development of the ENS phenotype and determined its functional repercussion on the neuromuscular transmission in the rat colon. Sprague-Dawley rats were euthanized at postnatal day (P) 1, P3, P5, P7, P14, P21, and P36. Whole mounts of colonic myenteric plexus were stained with antibodies against choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and HuC/D. Colonic contractile response induced by electrical field stimulation (EFS) was investigated in organ chambers in absence or presence of N-nitro-l-arginine methyl ester (l-NAME) and/or atropine. In vivo motility was assessed by measurement of the colonic bead latency time. Randomly occurring ex vivo contractions appeared starting at P5. Starting at P14, rhythmic phasic contractions occurred whose frequency and amplitude increased over time. In vivo, bead latency was significantly reduced between P14 and P21. Ex vivo, EFS-induced contractile responses increased significantly over time and were significantly reduced by atropine starting at P14 but were sensitive to l-NAME only after P21. The proportion of ChAT-immunoreactive (IR) neurons increased time dependently starting at P14. The proportion of nNOS-IR neurons increased as early as P5 compared with P1 but did not change afterward. Our data support a key role for cholinergic myenteric pathways in the development of postnatal motility and further identify them as putative therapeutic target for the treatment of GI motility disorders in the newborn.

  11. Long-term effect of early postnatal overnutrition on insulin resistance and serum fatty acid profiles in male rats.

    PubMed

    Bei, Fei; Jia, Jia; Jia, Yi-Qun; Sun, Jian-Hua; Liang, Fei; Yu, Zhong-Yi; Cai, Wei

    2015-08-26

    Increasing evidence suggests that overnutrition during the early postnatal period, a critical window of development, increases the risk of adult-onset obesity and insulin resistance. In this study, we investigated the impact of overnutrition during the suckling period on body weight, serum biochemistry and serum fatty acid metabolomics in male rats. Rats raised in small litters (SL, 3 pups/dam) and normal litters (NL, 10 pups/dam) were used to model early postnatal overnutrition and control, respectively. Serum glucose, triglyceride, high-density lipoprotein-cholesterol, free fatty acid, insulin and leptin concentrations were assayed using standard biochemical techniques. Serum fatty acids were identified and quantified using a gas chromatography-mass spectrometry-based metabolomic approach. mRNA and protein levels of key components of the insulin receptor signaling pathway were measured in epididymal fat and gastrocnemius muscle by quantitative PCR and western blotting. SL rats were 37.3 % and 15.1 % heavier than NL rats at weaning and 16-weeks-old, respectively. They had increased visceral fat mass, adult-onset insulin resistance and glucose intolerance as well as elevated serum levels of free fatty acids and triglycerides. All detectable fatty acids were elevated in the serum of SL pups at weaning compared to NL controls, and significant increases in the levels of four fatty acids (palmitic acid, palmitoleic acid, oleic acid and arachidonic acid) persisted into adulthood. Moreover, a significantly positive correlation was identified between an insulin resistance index (HOMA-IR) and concentrations of myristic, palmitic, palmitoleic and oleic acid in serum at postnatal 16 weeks. Early postnatal overnutrition also resulted in a significant downregulation of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) at the protein level in epididymal fat of SL rats at 16 weeks, accompanied by decreased mRNA levels for Irs-1 and

  12. Maternal postnatal psychiatric symptoms and infant temperament affect early mother-infant bonding.

    PubMed

    Nolvi, Saara; Karlsson, Linnea; Bridgett, David J; Pajulo, Marjukka; Tolvanen, Mimmi; Karlsson, Hasse

    2016-05-01

    Postnatal mother-infant bonding refers to the early emotional bond between mothers and infants. Although some factors, such as maternal mental health, especially postnatal depression, have been considered in relation to mother-infant bonding, few studies have investigated the role of infant temperament traits in early bonding. In this study, the effects of maternal postnatal depressive and anxiety symptoms and infant temperament traits on mother-infant bonding were examined using both mother and father reports of infant temperament. Data for this study came from the first phase of the FinnBrain Birth Cohort Study (n=102, father reports n=62). After controlling for maternal symptoms of depression and anxiety, mother-reported infant positive emotionality, measured by infant smiling was related to better mother-infant bonding. In contrast, infant negative emotionality, measured by infant distress to limitations was related to lower quality of bonding. In regards to father-report infant temperament, only infant distress to limitations (i.e., frustration/anger) was associated with lower quality of mother-infant bonding. These findings underline the importance of infant temperament as one factor contributing to early parent-infant relationships, and counseling parents in understanding and caring for infants with different temperament traits. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications.

    PubMed

    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michele; Alfano, Christian

    2016-01-27

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.

  14. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

    PubMed Central

    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

    2016-01-01

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

  15. GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex

    PubMed Central

    Anastasiades, Paul G.; Marques-Smith, Andre; Lyngholm, Daniel; Lickiss, Tom; Raffiq, Sayda; Kätzel, Dennis; Miesenböck, Gero; Butt, Simon J. B.

    2016-01-01

    GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain. PMID:26843463

  16. GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex.

    PubMed

    Anastasiades, Paul G; Marques-Smith, Andre; Lyngholm, Daniel; Lickiss, Tom; Raffiq, Sayda; Kätzel, Dennis; Miesenböck, Gero; Butt, Simon J B

    2016-02-04

    GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain.

  17. Early postnatal genistein administration permanently affects nitrergic and vasopressinergic systems in a sex-specific way.

    PubMed

    Ponti, G; Rodriguez-Gomez, A; Farinetti, A; Marraudino, M; Filice, F; Foglio, B; Sciacca, G; Panzica, G C; Gotti, S

    2017-03-27

    Genistein (GEN) is a natural xenoestrogen (isoflavonoid) that may interfere with the development of estrogen-sensitive neural circuits. Due to the large and increasing use of soy-based formulas for babies (characterized by a high content of GEN), there are some concerns that this could result in an impairment of some estrogen-sensitive neural circuits and behaviors. In a previous study, we demonstrated that its oral administration to female mice during late pregnancy and early lactation induced a significant decrease of nitric oxide synthase-positive cells in the amygdala of their male offspring. In the present study, we have used a different experimental protocol mimicking, in mice, the direct precocious exposure to GEN. Mice pups of both sexes were fed either with oil, estradiol or GEN from birth to postnatal day 8. Nitric oxide synthase and vasopressin neural systems were analyzed in adult mice. Interestingly, we observed that GEN effect was time specific (when compared to our previous study), sex specific, and not always comparable to the effects of estradiol. This last observation suggests that GEN may act through different intracellular pathways. Present results indicate that the effect of natural xenoestrogens on the development of the brain may be highly variable: a plethora of neuronal circuits may be affected depending on sex, time of exposure, intracellular pathway involved, and target cells. This raises concern on the possible long-term effects of the use of soy-based formulas for babies, which may be currently underestimated.

  18. Early Postnatal Hypotension and Developmental Delay at 24 Months of Age among Extremely Low Gestational Age Newborns

    PubMed Central

    Logan, J. Wells; O’Shea, T. Michael; Allred, Elizabeth N.; Laughon, Matthew M.; Bose, Carl L.; Dammann, Olaf; Batton, Daniel G.; Engelke, Stephen C.; Leviton, Alan

    2016-01-01

    Objectives To evaluate, in extremely low gestational age newborns (ELGANs), relationships between indicators of hypotension during the first 24 postnatal hours and developmental delay at 24 months of age. Methods The 945 infants in this prospective study were born at < 28 weeks, were assessed for 3 indicators of hypotension in the first 24 postnatal hours, and were evaluated with the Bayley Mental Development Index (MDI) and Psychomotor Development Index (PDI) at 24 months corrected age. Indicators of hypotension included: 1) mean arterial pressure (MAP) in the lowest quartile for gestational age; 2) treatment with a vasopressor; and 3) blood pressure lability, defined as the upper quartile for the difference between the lowest and highest MAP. Logistic regression was used to evaluate relationships between hypotension and developmental outcomes, adjusting for potential confounders. Results 26% of the cohort had an MDI < 70 and 32% had a PDI < 70. Low MDI and PDI were significantly associated with low gestational age, which in turn, was associated with receipt of vasopressor treatment. Blood pressure in the lowest quartile for gestational age was associated with vasopressor treatment and labile blood pressure. After adjusting for potential confounders, none of the indicators of hypotension was associated with MDI < 70 or PDI < 70. Conclusions In this large cohort of ELGANs, we found little evidence that early postnatal hypotension is associated with developmental delay at 24 months corrected gestational age. PMID:21138828

  19. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

    PubMed

    Doyle, Lex W; Ehrenkranz, Richard A; Halliday, Henry L

    2014-05-13

    Chronic lung disease remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat chronic lung disease because of their potent anti-inflammatory effects. To examine the relative benefits and adverse effects of postnatal corticosteroids commenced within the first seven days of life to preterm infants at risk of developing chronic lung disease. We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 8), MEDLINE (1966 to August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. We contacted authors of all studies, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. We selected RCTs of postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants for this review. Most studies evaluated the use of dexamethasone but we also included studies that assessed hydrocortisone, even if it was used primarily to manage hypotension. We extracted and analysed data regarding clinical outcomes that included mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications during the primary hospitalisation, and long-term health outcomes. Twenty-nine RCTs enrolling a total of 3750 participants were eligible for inclusion in this review. The overall risk for bias was probably low as all were randomised controlled trials, and most trials have used rigorous methods. There were significant benefits for the following outcomes: lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days and 36 weeks' postmenstrual age, death or chronic lung

  20. Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life.

    PubMed

    Kaňková, Sárka; Sulc, Jan; Křivohlavá, Romana; Kuběna, Aleš; Flegr, Jaroslav

    2012-11-01

    Toxoplasmosis, a zoonosis caused by a protozoan, Toxoplasma gondii, is probably the most widespread human parasitosis in developed countries. Pregnant women with latent toxoplasmosis have seemingly younger fetuses especially in the 16th week of gestation, which suggests that fetuses of Toxoplasma-infected mothers have slower rates of development in the first trimester of pregnancy. In the present retrospective cohort study, we analyzed data on postnatal motor development of infants from 331 questionnaire respondents including 53 Toxoplasma-infected mothers to search for signs of early postnatal development disorders. During the first year of life, a slower postnatal motor development was observed in infants of mothers with latent toxoplasmosis. These infants significantly later developed the ability to control the head position (p=0.039), to roll from supine to prone position (p=0.022) and were slightly later to begin crawling (p=0.059). Our results are compatible with the hypothesis that the difference in the rates of prenatal and early postnatal development between children of Toxoplasma-negative and Toxoplasma-positive mothers might be caused by a decreased stringency of embryo quality control in partly immunosuppressed Toxoplasma-positive mothers resulting in a higher proportion of infants with genetic or developmental disorders in offspring. However, because of relatively low return rate of questionnaires and an associated risk of a sieve effect, our results should be considered as preliminary and performing a large scale prospective study in the future is critically needed.

  1. Neurons in the corpus callosum of the cat during postnatal development.

    PubMed

    Riederer, Beat M; Berbel, Pere; Innocenti, Giorgio M

    2004-04-01

    The corpus callosum (CC) is a major telencephalic commissure containing mainly cortico-cortical axons and glial cells. We have identified neurons in the CC of the cat and quantified their number at different postnatal ages. An antibody against microtubule-associated protein 2 was used as a marker of neurons. Immunocytochemical double-labelling with neuron-specific enolase or gamma-aminobutyric acid antibodies in the absence of glial fibrillary acidic protein positivity confirmed the neuronal phenotype of these cells. CC neurons were also stained with anti-calbindin and anti-calretinin antibodies, typical for interneurons, and with an anti-neurofilament antibody, which in neocortex detects pyramidal neurons. Together, these findings suggest that the CC contains a mixed population of neuronal types. The quantification was corrected for double counting of adjacent sections and volume changes during CC development. Our data show that CC neurons are numerous early postnatally, and their number decreases with age. At birth, about 570 neurons are found within the CC boundaries and their number drops to about 200 in the adult. The distribution of the neurons within the CC also changes in development. Initially, many neurons are found throughout the CC, while at later ages they become restricted to the boundaries of the CC, and in the adult to the rostrum of the CC close to the septum pellucidum or to the indusium griseum. Although origin and function of transient CC neurons in development and in adulthood remain unknown, they are likely to be interstitial neurons. Some of them have well-developed and differentiated processes and resemble pyramidal cells or interneurons. An axon-guiding function during the early postnatal period can not be excluded.

  2. Postnatal development of renal function: micropuncture and clearance studies in the dog

    PubMed Central

    Horster, Michael; Valtin, Heinz

    1971-01-01

    Postnatal renal development was studied in dogs between 2 and 77 days. Single, superficial nephrons were evaluated by micropuncture, concurrently with measurements of total renal function and morphometric analyses in the same animals. Glomerular filtration rate for the entire kidney increased linearly from 0.13 ml/min per g kidney weight at 2 days to 0.91 at 77 days. Extraction of p-aminohippurate increased from about 20 to 80%, and renal plasma flow per g kidney weight, measured as Cpah/Epah, increased threefold during the same period. Filtration fraction increased to the mature value during the first half of the postnatal period studied. The clearance of urea per unit of renal mass increased with age, whereas the fraction of filtered urea reabsorbed declined during the early part of the postnatal period. The pattern of fractional urea reabsorption may be due mainly to increased medullary recycling of urea and to a rise in the reabsorption of water from the medullary collecting duct. Urine osmolality was higher than plasma from birth onward and rose with age. Osmolal equality of collecting duct fluid and medullary interstitium reflected mature vasopressin (ADH)-induced water permeability. The rise in urinary concentration was predominantly due to increasing medullary sequestration of urea. Glomerular filtration rate of the superficial nephron increased from 3.2 nl/min at 21 days, when subcapsular nephrons were uniformly patent, to 23.1 at 77 days. Despite this rise in filtered load, fractional reabsorption of sodium and water in superficial proximal tubules was constant and at the mature level from the onset of intratubular perfusion. Changes in arterial plasma protein concentration, in filtration fraction, and in the hydrostatic pressure gradient between proximal tubule and peritubular capillary may interact to maintain glomerulotubular balance. The data, together with results of an accompanying morphological study, demonstrate a sequence of coordinated changes

  3. [The effect of cadmium on the wakefulness-sleep cycle in rats in early postnatal ontogeny].

    PubMed

    Aristakesian, E A; Kiiashchenko, L I; Oganesian, G A

    1996-01-01

    The influence of cadmium chloride on behavioural and EEC characteristics of sleep-wakefulness cycle in the newborn Wistar rats (from the 5th to the 14th day of life) was investigated under conditions of the acute and chronic experiment. It is found that single injection of cadmium has caused the increase in wakefulness time. The slow and active sleep stage duration became shorter for three times. The moderate increase in alpha-range wave power for both stages of sleep is a characteristic of EEG for sleep on the background of the acute cadmium injection. The chronic injection of toxic matter is accompanied by appearance of cataleptic state in the sleep-wakefulness cycle. Its intensity increases for 2 weeks with every new injection. The electron-microscopic investigation of nerve fibers of caudate putamen and corpus callosum conducted on animals 2 weeks old (in a week after the last injection) has found the nerve fibers demyelination, increase in share of microtubules compared to neurofilaments. All these features are typical for earlier postnatal period of the brain development (the 4-5th day of life). It is suggested that under the chronic injection in the early ontogenesis cadmium penetrates through hematoencephalic barrier and induces the structural and functional CNS organization delay.

  4. Initial stages of radial glia astrocytic transformation in the early postnatal anterior subventricular zone.

    PubMed

    Alves, José A J; Barone, Patrick; Engelender, Simone; Fróes, Maira M; Menezes, João R L

    2002-09-05

    In the early postnatal subventricular zone (SVZ), two seemingly unrelated events occur simultaneously: a massive tangential migration of neuroblasts towards the olfactory bulb, known as the rostral migratory stream (RMS), and the outward movement of radial glia (RG) undergoing astrocytic transformation. Because of the orthogonal arrangement between these two sets of cells, little, if any, relevance has been ascribed for their possible interactions. By depositing DiI at the pial surface we have studied RG transformation within the SVZ/RMS, from birth up to the end of the first postnatal week. While still within the SVZ/RMS, RG morphology changed from simple bipolar to highly complex branched profiles, attaining their highest degree of complexity at the interface of the SVZ with the overlying white matter. At this interface cell bodies of radial glia accumulate and their processes run tangentially, surrounding the SVZ/RMS. Processes of RG surrounding the SVZ/RMS could also be observed by immunostaining for vimentin, GFAP, and nestin. In contrast, in the white matter all DiI-labeled RG presented a simple bipolar profile. These results indicate that the outward radial migration of the transforming RG does not occur uniformly. Instead, the different morphologies and cell densities that RG assume when they cross the SVZ/RMS and overlying white matter imply different migratory behaviors. Finally, our data suggest that RG provide a cellular scaffold to the early postnatal SVZ/RMS, much in the same way as astrocytes in the adult RMS.

  5. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    PubMed

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Prenatal and early postnatal depression and child maltreatment among Japanese fathers.

    PubMed

    Takehara, Kenji; Suto, Maiko; Kakee, Naoko; Tachibana, Yoshiyuki; Mori, Rintaro

    2017-08-01

    We investigated the association of paternal depression in the prenatal and early postnatal period with child maltreatment tendency at two months postpartum among Japanese fathers. This population-based longitudinal study recruited Japanese perinatal women and their partners living in Nishio City, Aichi, Japan. Of the 270 fathers who participated, 196 were included in the analysis. All data were collected via self-administrated questionnaires at four time points: 20 weeks' gestation and in the first few days, one month, and two months postpartum. Paternal depression was assessed using the Edinburgh Postnatal Depression Scale. Three definitions of paternal depression were coded based on participants' scores on this measure: prenatal, prior, and current. Child maltreatment tendency was evaluated using the Child Maltreatment Scale at two months postpartum. The associations of the three definitions of paternal depression and child maltreatment tendency were separately analyzed using logistic regression analysis. The prevalence of prenatal, prior, and current paternal depression was 9.7%, 10.2%, and 8.8%, respectively. According to the multivariate analysis, current paternal depression was significantly associated with child maltreatment tendency at two months postpartum (adjusted odds ratio: 7.77, 95% CI: 1.83-33.02). The other two types of depression, however, were not related to child maltreatment tendency. Thus, current paternal depression increased the risk of child maltreatment tendency in the postnatal period, suggesting that early detection and treatment of paternal depression might be useful for the prevention of child maltreatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Postnatal dendritic development of Y-like geniculocortical relay neurons.

    PubMed

    Coleman, Lee-Ann; Friedlander, Michael J

    2002-01-01

    We describe the dendritic development of neurons in the dorsal lateral geniculate nucleus (LGNd) projecting to cortical area 18 in the postnatal cat. LGN neurons were identified by retrograde labeling from area 18 with fluorescent latex microspheres and injected in the fixed slice with Lucifer yellow (LY) and horseradish peroxidase (HRP) to visualize their dendritic arborizations. Both topological (measures of the patterns of dendritic branching and their territorial coverage) and metric parameters (measures of the quantitative parameters describing the size, length, extent and diameter of the dendritic arbors) were measured in three-dimensions for 25 LGN neurons in cats between 1 and 18 postnatal weeks. In addition, dendritic growth was compared to the changing dimensions of the LGNd. At all ages, neurons projecting to area 18 have large somata and radiate dendrites. From 1 to 18 weeks neurons increase in size--both soma area and the length of all dendritic segments double during this period. Intermediate and terminal dendritic segments show comparable growth until 5 weeks. However, only terminal segments continue to grow significantly from 5 until 18 weeks. Dendrites become straighter during development, the angle between daughter branches decreases and dendritic segment diameter increases, with terminal segments showing a greater increase relative to intermediate segments. The density of dendritic appendages increases transiently at 5 weeks and a differential redistribution occurs, so that by 18 weeks dendrites further from the soma have a greater density of appendages than those near the soma. Some dendritic relationships remain invariant during development--intermediate segments are always shorter, thicker and straighter than terminal segments. During these changes however, area 18 projecting neurons maintain a constant number of primary dendrites and have, on average, a constant branching pattern. The relative volume of the LGNd occupied by an area 18

  8. Postnatal development under conditions of simulated weightlessness and space flight

    NASA Technical Reports Server (NTRS)

    Walton, K.

    1998-01-01

    The adaptability of the developing nervous system to environmental influences and the mechanisms underlying this plasticity has recently become a subject of interest in space neuroscience. Ground studies on neonatal rats using the tail suspension model of weightlessness have shown that the force of gravity clearly influences the events underlying the postnatal development of motor function. These effects depend on the age of the animal, duration of the perturbation and the motor function studied. A nine-day flight study has shown that a dam and neonates can develop under conditions of space flight. The motor function of the flight animals after landing was consistent with that seen in the tail suspension studies, being marked by limb joint extension. However, there were expected differences due to: (1) the unloading of the vestibular system in flight, which did not occur in the ground-based experiments; (2) differences between flight and suspension durations; and (3) the inability to evaluate motor function during the flight. The next step is to conduct experiments in space with the flexibility and rigor that is now limited to ground studies: an opportunity offered by the International Space Station. Copyright 1998 Published by Elsevier Science B.V.

  9. Postnatal development under conditions of simulated weightlessness and space flight

    NASA Technical Reports Server (NTRS)

    Walton, K.

    1998-01-01

    The adaptability of the developing nervous system to environmental influences and the mechanisms underlying this plasticity has recently become a subject of interest in space neuroscience. Ground studies on neonatal rats using the tail suspension model of weightlessness have shown that the force of gravity clearly influences the events underlying the postnatal development of motor function. These effects depend on the age of the animal, duration of the perturbation and the motor function studied. A nine-day flight study has shown that a dam and neonates can develop under conditions of space flight. The motor function of the flight animals after landing was consistent with that seen in the tail suspension studies, being marked by limb joint extension. However, there were expected differences due to: (1) the unloading of the vestibular system in flight, which did not occur in the ground-based experiments; (2) differences between flight and suspension durations; and (3) the inability to evaluate motor function during the flight. The next step is to conduct experiments in space with the flexibility and rigor that is now limited to ground studies: an opportunity offered by the International Space Station. Copyright 1998 Published by Elsevier Science B.V.

  10. Risk of Childhood Overweight after Exposure to Tobacco Smoking in Prenatal and Early Postnatal Life

    PubMed Central

    Ajslev, Teresa Adeltoft; Andersen, Camilla Schou; Dalgård, Christine; Sørensen, Thorkild I. A.

    2014-01-01

    Objective To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. Methods From the Danish National Birth Cohort a total of 32,747 families were identified with available information on maternal smoking status in child's pre- and postnatal life and child's birth weight, and weight and height at age 7 years. Outcome was overweight according to the International Obesity Task Force gender and age specific body mass index. Smoking exposure was categorized into four groups: no exposure (n = 25,076); exposure only during pregnancy (n = 3,343); exposure only postnatally (n = 140); and exposure during pregnancy and postnatally (n = 4,188). Risk of overweight according to smoking status as well as dose-response relationships were estimated by crude and adjusted odds ratios using logistic regression models. Results Exposure to smoking only during pregnancy, or both during pregnancy and postnatally were both significantly associated with overweight at 7 years of age (OR: 1.31, 95% CI: 1.15–1.48, and OR: 1.76, 95% CI: 1.58–1.97, respectively). Analyses excluding children with low birth weight (<2,500 gram) revealed similar results. A significant prenatal dose-response relationship was found. Per one additional cigarette smoked per day an increase in risk of overweight was observed (OR: 1.02, 95% CI: 1.01–1.03). When adjusting for quantity of smoking during pregnancy, prolonged exposure after birth further increased the risk of later overweight in the children (OR 1.28, 95% CI:1.09–1.50) compared with exposure only in the prenatal period. Conclusions Mother's perinatal smoking increased child's OR of overweight at age 7 years irrespective of birth weight, and with higher OR if exposed both during pregnancy and in early postnatal life. Clear dose-response relationships were observed, which emphasizes the need for prevention of

  11. UNC-Emory Infant Atlases for Macaque Brain Image Analysis: Postnatal Brain Development through 12 Months

    PubMed Central

    Shi, Yundi; Budin, Francois; Yapuncich, Eva; Rumple, Ashley; Young, Jeffrey T.; Payne, Christa; Zhang, Xiaodong; Hu, Xiaoping; Godfrey, Jodi; Howell, Brittany; Sanchez, Mar M.; Styner, Martin A.

    2017-01-01

    Computational anatomical atlases have shown to be of immense value in neuroimaging as they provide age appropriate reference spaces alongside ancillary anatomical information for automated analysis such as subcortical structural definitions, cortical parcellations or white fiber tract regions. Standard workflows in neuroimaging necessitate such atlases to be appropriately selected for the subject population of interest. This is especially of importance in early postnatal brain development, where rapid changes in brain shape and appearance render neuroimaging workflows sensitive to the appropriate atlas choice. We present here a set of novel computation atlases for structural MRI and Diffusion Tensor Imaging as crucial resource for the analysis of MRI data from non-human primate rhesus monkey (Macaca mulatta) data in early postnatal brain development. Forty socially-housed infant macaques were scanned longitudinally at ages 2 weeks, 3, 6, and 12 months in order to create cross-sectional structural and DTI atlases via unbiased atlas building at each of these ages. Probabilistic spatial prior definitions for the major tissue classes were trained on each atlas with expert manual segmentations. In this article we present the development and use of these atlases with publicly available tools, as well as the atlases themselves, which are publicly disseminated to the scientific community. PMID:28119564

  12. Gap junctions are involved in cell migration in the early postnatal subventricular zone.

    PubMed

    Marins, Mônica; Xavier, Anna L R; Viana, Nathan B; Fortes, Fábio S A; Fróes, Maira M; Menezes, João R L

    2009-09-15

    The massive migration of neuroblasts and young neurons through the anterior extension of the postnatal subventricular zone (SVZ), known as the rostral migratory stream (RMS) is still poorly understood on its molecular basis. In this work, we investigated the involvement of gap junctional communication (GJC) in the robust centrifugal migration from SVZ/RMS explants obtained from early postnatal (P4) rats. Cells were dye-coupled in homocellular and heterocellular pairings and expressed at least two connexins, Cx 43 and 45. Treatment with the uncoupler agent carbenoxolone (CBX, 10-100 microM) reversibly reduced outgrowth from SVZ explants, while its inactive analog, glycyrhizinic acid (GZA), had no effect. Consistent with a direct effect on cell migration, time-lapse video microscopy show that different pharmacological uncouplers cause an abrupt and reversible arrest of cell movement in explants. Our results indicate that GJC is positively involved in the migration of neuroblasts within the SVZ/RMS.

  13. Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

    PubMed

    Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

    2015-01-01

    Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. E2f8 mediates tumor suppression in postnatal liver development

    PubMed Central

    Kent, Lindsey N.; Rakijas, Jessica B.; Pandit, Shusil K.; Westendorp, Bart; Chen, Hui-Zi; Huntington, Justin T.; Tang, Xing; Bae, Sooin; Srivastava, Arunima; Senapati, Shantibhusan; Martin, Chelsea K.; Cuitino, Maria C.; Perez, Miguel; Clouse, Julian M.; Chokshi, Veda; Shinde, Neelam; Kladney, Raleigh; Sun, Daokun; Perez-Castro, Antonio; Matondo, Ramadhan B.; Nantasanti, Sathidpak; Mokry, Michal; Machiraju, Raghu; Fernandez, Soledad; Rosol, Thomas J.; Pohar, Kamal S.; Pipas, James M.; Schmidt, Carl R.; de Bruin, Alain

    2016-01-01

    E2F-mediated transcriptional repression of cell cycle–dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hepatocellular carcinoma (HCC). Here, we evaluated the function of the atypical repressor genes E2f7 and E2f8 in adult liver physiology. Using several loss-of-function alleles in mice, we determined that combined deletion of E2f7 and E2f8 in hepatocytes leads to HCC. Temporal-specific ablation strategies revealed that E2f8’s tumor suppressor role is critical during the first 2 weeks of life, which correspond to a highly proliferative stage of postnatal liver development. Disruption of E2F8’s DNA binding activity phenocopied the effects of an E2f8 null allele and led to HCC. Finally, a profile of chromatin occupancy and gene expression in young and tumor-bearing mice identified a set of shared targets for E2F7 and E2F8 whose increased expression during early postnatal liver development is associated with HCC progression in mice. Increased expression of E2F8-specific target genes was also observed in human liver biopsies from HCC patients compared to healthy patients. In summary, these studies suggest that E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development. PMID:27454291

  15. Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

    PubMed

    Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

    2017-11-01

    The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α1-adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

  16. Postnatal and adult neurogenesis in the development of human disease.

    PubMed

    Danzer, Steve C

    2008-10-01

    The mammalian brain contains a population of neurons that are continuously generated from late embryogenesis through adulthood-after the generation of almost all other neuronal types. This brain region-the hippocampal dentate gyrus-is in a sense, therefore, persistently immature. Postnatal and adult neurogenesis is likely an essential feature of the dentate, which is critical for learning and memory. Protracted neurogenesis after birth would allow the new cells to develop in conjunction with external events-but it may come with a price: while neurogenesis in utero occurs in a protected environment, children and adults are exposed to any number of hazards, such as toxins and infectious agents. Mature neurons might be resistant to such exposures, but new neurons may be vulnerable. Consistent with this prediction, in adult rodents seizures disrupt the integration of newly generated granule cells, whereas mature granule cells are comparatively unaffected. Significantly, abnormally interconnected cells may contribute to epileptogenesis and/or associated cognitive and memory deficits. Finally, studies increasingly indicate that new granule cells are extremely sensitive to a host of endogenous and exogenous factors, raising the possibility that disrupted granule cell integration may be a common feature of many neurological diseases.

  17. Gestational medication use, birth conditions, and early postnatal exposures for childhood asthma.

    PubMed

    Chen, Yang-Ching; Tsai, Ching-Hui; Lee, Yungling

    2012-01-01

    Our aim is to explore (1) whether gestational medication use, mode of delivery, and early postnatal exposure correlate with childhood asthma, (2) the dose responsiveness of such exposure, and (3) their links to early- and late-onset asthma. We conducted a matched case-control study based on the Taiwan Children Health Study, which was a nationwide survey that recruited 12-to-14-year-old school children in 14 communities. 579 mothers of the participants were interviewed by telephone. Exclusive breastfeeding protected children from asthma. Notably, childhood asthma was significantly associated with maternal medication use during pregnancy, vacuum use during vaginal delivery, recurrent respiratory tract infections, hospitalization, main caregiver cared for other children, and early daycare attendance. Exposure to these factors led to dose responsiveness in relationships to asthma. Most of the exposures revealed a greater impact on early-onset asthma, except for vacuum use and daycare attendance.

  18. Gestational Medication Use, Birth Conditions, and Early Postnatal Exposures for Childhood Asthma

    PubMed Central

    Chen, Yang-Ching; Tsai, Ching-Hui; Lee, Yungling

    2012-01-01

    Our aim is to explore (1) whether gestational medication use, mode of delivery, and early postnatal exposure correlate with childhood asthma, (2) the dose responsiveness of such exposure, and (3) their links to early- and late-onset asthma. We conducted a matched case-control study based on the Taiwan Children Health Study, which was a nationwide survey that recruited 12-to-14-year-old school children in 14 communities. 579 mothers of the participants were interviewed by telephone. Exclusive breastfeeding protected children from asthma. Notably, childhood asthma was significantly associated with maternal medication use during pregnancy, vacuum use during vaginal delivery, recurrent respiratory tract infections, hospitalization, main caregiver cared for other children, and early daycare attendance. Exposure to these factors led to dose responsiveness in relationships to asthma. Most of the exposures revealed a greater impact on early-onset asthma, except for vacuum use and daycare attendance. PMID:22203862

  19. Antenatal and early postnatal antecedents of parent-reported attention problems at 2 years of age.

    PubMed

    Downey, L Corbin; O'Shea, T Michael; Allred, Elizabeth N; Kuban, Karl; McElrath, Thomas F; Warner, Diane D; Ware, Janice; Hecht, Jonathan L; Onderdonk, Andrew; Leviton, Alan

    2015-01-01

    To assess antenatal and early postnatal antecedents of attention problems identified by the Child Behavior Checklist in extremely preterm children. In a cohort of 826 children born between 23 and 27 weeks' gestation, we collected demographic, birth, and postnatal information. We then identified behavior problems by using parent ratings from the Child Behavior Checklist at 2 years' adjusted age. We created time-oriented logistic regression risk models to identify significant risk factors for attention problems and Diagnostic and Statistical Manual of Mental Disorders-compatible attention deficit/hyperactivity problems (ADHP(DSM)). Children were at increased risk of both attention problems if they were born to a woman who had no formal education beyond high school and/or a woman who was exposed to secondhand smoke. Recovery of a single organism from the placenta was associated with increased risk of an attention problem, and fetal stem vessel thrombosis and recovery of Mycoplasma species were associated with increased risk of ADHP(DSM). Infants of multifetal gestations were at reduced risk of both attention problems. The only postnatal risk factor for an attention problem was recovery of bacteria from a tracheal aspirate. Among extremely preterm infants, several potentially modifiable antenatal and perinatal antecedents are associated with increased risk for attention problems and ADHP(DSM) at 2 years adjusted age. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Alterations in nuclear envelope invaginations in axotomized fetal and early postnatal hamster facial motoneurons.

    PubMed

    Clark, P; Jones, K J; LaVelle, A

    1992-07-24

    In this study, changes in the amount of nuclear envelope invaginations (NEI) were morphometrically assessed after axotomy during late fetal and early postnatal developmental stages in hamster facial motoneurons. These changes were expressed as boundary density or BA (length of nuclear envelope per unit area of nucleus). Axotomy-induced changes in nuclear area and perimeter were also quantitatively determined. At 17 h after axotomy in the fetal operative series, no changes in any of the parameters were seen. At 1 day postoperative (dpo) in newborn, 2 and 4 postnatal day animals, the boundary densities of the total and invaginated portion of the nuclear envelope increased significantly. No corresponding qualitative changes were observed. At 2 dpo in 4 and 7 postnatal day animals, there were significant increases in the boundary densities of both invaginated and total nuclear envelope and a decrease in nuclear area. These changes were not seen at 2 dpo in the 9-day operative series. At 4 dpo in 7 and 9 postnatal day animals, scalloping of the normally smooth nuclear profile, as well as a flattening and elongation in nuclear shape, occurred. These qualitative changes in the 7 and 9 day operated groups were also accompanied by significant changes in all the measured parameters. The boundary density of the invaginated, non-invaginated and total nuclear envelope increased; whereas, nuclear area and perimeter decreased. These results argue against the generally held hypothesis that an increase in nuclear envelope invaginations is indicative of an allied increase in cellular metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. An association of adult personality with prenatal and early postnatal growth: the EPQ lie-scale.

    PubMed

    Flensborg-Madsen, Trine; Revsbech, Rasmus; Sørensen, Holger Jelling; Mortensen, Erik Lykke

    2014-01-01

    Recent studies have noted differences in social acquiescence and interpersonal relations among adults born preterm or with very low birth weight compared to full term adults. In addition, birth weight has been observed to be negatively correlated with lie-scale scores in two studies. We attempted to replicate and extend these studies by examining young adult lie-scale scores in a Danish birth cohort. Weight, length and head circumference of 9125 children from the Copenhagen Perinatal Cohort were measured at birth and at 1, 3 and 6 years. A subsample comprising 1182 individuals participated in a follow-up at 20-34 years and was administered the Eysenck Personality Questionnaire (EPQ) which includes a lie-scale (indicating social acquiescence or self-insight). Associations between lie-scale scores and weight, length and head circumference respectively were analysed by multiple linear regression adjusting for single-mother status, parity, mother's age, father's age, parental social status, age at EPQ measurement, intelligence, and adult size. Male infants with lower weight, length, and head-circumference at birth and the following three years grew up to have higher scores on the lie-scale as young adults. Most of these associations remained significant after adjustment for the included covariates. No associations were found for females. Analyses were also conducted with neuroticism, extraversion and psychoticism as outcome variables, but no significant associations were found for these traits after adjustment. The findings replicate and extend findings from previous studies suggesting that size at birth and during the first three years of life is significantly associated with social acquiescence in adult men. They highlight the potential influence of prenatal and early postnatal development on personality growth and development.

  2. Usp9x-deficiency disrupts the morphological development of the postnatal hippocampal dentate gyrus

    PubMed Central

    Oishi, Sabrina; Premarathne, Susitha; Harvey, Tracey J.; Iyer, Swati; Dixon, Chantelle; Alexander, Suzanne; Burne, Thomas H. J.; Wood, Stephen A.; Piper, Michael

    2016-01-01

    Within the adult mammalian brain, neurogenesis persists within two main discrete locations, the subventricular zone lining the lateral ventricles, and the hippocampal dentate gyrus. Neurogenesis within the adult dentate gyrus contributes to learning and memory, and deficiencies in neurogenesis have been linked to cognitive decline. Neural stem cells within the adult dentate gyrus reside within the subgranular zone (SGZ), and proteins intrinsic to stem cells, and factors within the niche microenvironment, are critical determinants for development and maintenance of this structure. Our understanding of the repertoire of these factors, however, remains limited. The deubiquitylating enzyme USP9X has recently emerged as a mediator of neural stem cell identity. Furthermore, mice lacking Usp9x exhibit a striking reduction in the overall size of the adult dentate gyrus. Here we reveal that the development of the postnatal SGZ is abnormal in mice lacking Usp9x. Usp9x conditional knockout mice exhibit a smaller hippocampus and shortened dentate gyrus blades from as early as P7. Moreover, the analysis of cellular populations within the dentate gyrus revealed reduced stem cell, neuroblast and neuronal numbers and abnormal neuroblast morphology. Collectively, these findings highlight the critical role played by USP9X in the normal morphological development of the postnatal dentate gyrus. PMID:27181636

  3. Conditional overexpression of connective tissue growth factor disrupts postnatal lung development.

    PubMed

    Wu, Shu; Platteau, Astrid; Chen, Shaoyi; McNamara, George; Whitsett, Jeffrey; Bancalari, Eduardo

    2010-05-01

    Connective tissue growth factor (CTGF) is a member of an emerging family of immediate-early gene products that coordinates complex biological processes during development, differentiation, and tissue repair. Overexpression of CTGF is associated with mechanical ventilation with high tidal volume and oxygen exposure in newborn lungs. However, the role of CTGF in postnatal lung development and remodeling is not well understood. In the present study, a double-transgenic mouse model was generated with doxycycline-inducible overexpression of CTGF in respiratory epithelial cells. Overexpression of CTGF from Postnatal Days 1-14 resulted in thicker alveolar septa and decreased secondary septal formation. This is correlated with increased myofibroblast differentiation and disorganized elastic fiber deposition in alveolar septa. Overexpression of CTGF also decreased alveolar capillary network formation. There were increased alpha-smooth muscle actin expression and collagen deposition, and dramatic thickening in the peribronchial/peribronchiolar and perivascular regions in the double-transgenic lungs. Furthermore, overexpression of CTGF increased integrin-linked kinase expression, activated its downstream signaling target, Akt, as well as increased mRNA expression of fibronectin. These data demonstrate that overexpression of CTGF disrupts alveologenesis and capillary formation, and induces fibrosis during the critical period of alveolar development. These histologic changes are similar to those observed in lungs of infants with bronchopulmonary dysplasia.

  4. Orexin-A and orexin-B during the postnatal development of the rat brain.

    PubMed

    Stoyanova, Irina I; Rutten, Wim L C; le Feber, Joost

    2010-01-01

    Orexin-A and orexin-B are hypothalamic neuropeptides isolated from a small group of neurons in the hypothalamus, which project their axons to all major parts of the central nervous system. Despite the extensive information about orexin expression and function at different parts of the nervous system in adults, data about the development and maturation of the orexin system in the brain are a bit contradictory and insufficient. A previous study has found expression of orexins in the hypothalamus after postnatal day 15 only, while others report orexins detection at embryonic stages of brain formation. In the present study, we investigated the distribution of orexin-A and orexin-B neuronal cell bodies and fibers in the brain at three different postnatal stages: 1-week-, 2-week-old and adult rats. By means of immunohistochemical techniques, we demonstrated that a small subset of cells in the lateral hypothalamus, and the perifornical and periventricular areas were orexin-A and orexin-B positive not only in 2-week-old and adult rats but also in 1-week-old animals. In addition, orexin-A and orexin-B expressing neuronal varicosities were found in many other brain regions. These results suggest that orexin-A and orexin-B play an important role in the early postnatal brain development. The widespread distribution of orexinergic projections through all these stages may imply an involvement of the two neurotransmitters in a large variety of physiological and behavioral processes also including higher brain functions like learning and memory.

  5. Implications of Post-Natal Cortical Development for Creativity Research.

    ERIC Educational Resources Information Center

    Gordon, Marjory; Dacey, John

    Man's long period of cerebral growth has important implications for education. The brain goes through major developmental changes after birth, and researchers have suggested that this growth process presents an opportunity for fostering the plasticity of genetically determined connections. Animal studies show that postnatal growth of the brain is…

  6. Postnatal development of bile secretory physiology in the dog

    SciTech Connect

    Tavoloni, N.; Jones, M.J.; Berk, P.D.

    1985-04-01

    To determine whether bile formation in the dog is an immature process at birth, several determinants of bile secretion were studied in anesthetized, bile duct-cannulated puppies of 0-42 days of age and adult dogs. Basal canalicular bile flow rate, estimated by /sup 14/C-erythritol biliary clearance, averaged 0.182 microliter/min/g liver in 0-3 day-old puppies and increased to 0.324 and 0.461 microliter/min/g in puppies 7-21 and 28-42 days of age, respectively. Calculated ductular bile water reabsorption (/sup 14/C-erythritol biliary clearance-bile flow) was virtually absent in 0-3 day-old puppies, and averaged 0.017 and 0.092 microliter/min/g in puppies of 7-21 and 28-42 days of age, respectively. In adult dogs, ductular bile water reabsorption was 0.132 microliter/min/g. These functional deficiencies of the newborn dog were associated with an increased biliary permeability to /sup 3/H-inulin which could not be accounted for solely by an increased solute diffusion due to the lower rate of canalicular bile flow. Administration of taurocholate up to 2000 nmol/min/kg produced in all animals a similar increase in canalicular bile flow and bile acid excretion, and was not associated with changes in ductular bile water reabsorption rate. These findings are interpreted to indicate that, in the dog, bile secretory function is immature at birth and develops during postnatal life.

  7. Maternal postnatal mental health and later emotional-behavioural development of children: the mediating role of parenting behaviour.

    PubMed

    Giallo, R; Cooklin, A; Wade, C; D'Esposito, F; Nicholson, J M

    2014-05-01

    Maternal postnatal mental health difficulties have been associated with poor outcomes for children. One mechanism by which parent mental health can impact on children's outcomes is via its effects on parenting behaviour. The longitudinal relationships between maternal postnatal distress, parenting warmth, hostility and child well-being at age seven were examined for 2200 families participating in a population-based longitudinal study of Australian children. The relationship between postnatal distress and children's later emotional-behavioural development was mediated by parenting hostility, but not parenting warmth, even after accounting for concurrent maternal mental health. Postnatal distress was more strongly associated with lower parenting warmth for mothers without a past history of depression compared with mothers with a past history of depression. These findings underscore the contribution of early maternal well-being to later parenting and child outcomes, highlighting the importance of mental health and parenting support in the early parenting years. Implications for policy and practice are discussed. © 2013 John Wiley & Sons Ltd.

  8. Spatial distributions of AQP5 and AQP0 in embryonic and postnatal mouse lens development

    PubMed Central

    Petrova, Rosica S.; Schey, Kevin L.; Donaldson, Paul J.; Grey, Angus C.

    2015-01-01

    The expression of the water channel protein aquaporin (AQP)-5 in adult rodent and human lenses was recently reported using immunohistochemistry, molecular biology, and mass spectrometry techniques, confirming a second transmembrane water channel that is present in lens fibre cells in addition to the abundant AQP0 protein. Interestingly, the sub-cellular distribution and level of post-translational modification of both proteins changes with fibre cell differentiation and location in the adult rodent lens. This study compares the sub-cellular distribution of AQP0 and AQP5 during embryonic and postnatal fibre cell development in the mouse lens to understand how the immunolabelling patterns for both AQPs observed in adult lens are first established. Immunohistochemistry was used to map the cellular and sub-cellular distribution of AQP5 and AQP0 throughout the lens in cryosections from adult (6 weeks to 8 months) and postnatal (0-2 weeks) mouse lenses and in sections from paraffin embedded mouse embryos (E10-E19). All sections were imaged by fluorescence confocal microscopy. Using antibodies directed against the C-terminus of each AQP, AQP5 was abundantly expressed early in development, being found in the cytoplasm of cells of the lens vesicle and surrounding tissues (E10), while AQP0 was detected later (E11), and only in the membranes of elongating primary fibre cells. During the course of subsequent embryonic and postnatal development the pattern of cytoplasmic AQP5 and membranous AQP0 labelling was maintained until postnatal day 6 (P6). From P6 AQP5 labelling became progressively more membranous initially in the lens nucleus and then later in all regions of the lens, while AQP0 labelling was abruptly lost in the lens nucleus due to C-terminal truncation. Our results show that the spatial distribution patterns of AQP0 and AQP5 observed in the adult lens are established during a narrow window of post natal development (P6-P15) that precedes eye opening and coincides

  9. Notch Signaling Limits Supporting Cell Plasticity in the Hair Cell-Damaged Early Postnatal Murine Cochlea

    PubMed Central

    Korrapati, Soumya; Roux, Isabelle; Glowatzki, Elisabeth; Doetzlhofer, Angelika

    2013-01-01

    In mammals, auditory hair cells are generated only during embryonic development and loss or damage to hair cells is permanent. However, in non-mammalian vertebrate species, such as birds, neighboring glia-like supporting cells regenerate auditory hair cells by both mitotic and non-mitotic mechanisms. Based on work in intact cochlear tissue, it is thought that Notch signaling might restrict supporting cell plasticity in the mammalian cochlea. However, it is unresolved how Notch signaling functions in the hair cell-damaged cochlea and the molecular and cellular changes induced in supporting cells in response to hair cell trauma are poorly understood. Here we show that gentamicin-induced hair cell loss in early postnatal mouse cochlear tissue induces rapid morphological changes in supporting cells, which facilitate the sealing of gaps left by dying hair cells. Moreover, we provide evidence that Notch signaling is active in the hair cell damaged cochlea and identify Hes1, Hey1, Hey2, HeyL, and Sox2 as targets and potential Notch effectors of this hair cell-independent mechanism of Notch signaling. Using Cre/loxP based labeling system we demonstrate that inhibition of Notch signaling with a γ- secretase inhibitor (GSI) results in the trans-differentiation of supporting cells into hair cell-like cells. Moreover, we show that these hair cell-like cells, generated by supporting cells have molecular, cellular, and basic electrophysiological properties similar to immature hair cells rather than supporting cells. Lastly, we show that the vast majority of these newly generated hair cell-like cells express the outer hair cell specific motor protein prestin. PMID:24023676

  10. Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic–Ischemic Fetal Lambs during Postnatal Life

    PubMed Central

    Rey-Santano, Carmen; Mielgo, Victoria E.; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-del-Yerro, Estibaliz; Valls-i-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J.

    2011-01-01

    The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic–ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury. PMID:21960958

  11. Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life.

    PubMed

    Xu, Le; Yang, Yang; Gao, Lixiong; Zhao, Jinghui; Cai, Yulong; Huang, Jing; Jing, Sheng; Bao, Xiaohang; Wang, Ying; Gao, Junwei; Xu, Haiwei; Fan, Xiaotang

    2015-07-01

    Ethanol (EtOH) exposure during early postnatal life triggers obvious neurotoxic effects on the developing hippocampus and results in long-term effects on hippocampal neurogenesis. Resveratrol (RSV) has been demonstrated to exert potential neuroprotective effects by promoting hippocampal neurogenesis. However, the effects of RSV on the EtOH-mediated impairment of hippocampal neurogenesis remain undetermined. Thus, mice were pretreated with RSV and were later exposed to EtOH to evaluate its protective effects on EtOH-mediated toxicity during hippocampal development. The results indicated that a brief exposure of EtOH on postnatal day 7 resulted in a significant impairment in hippocampal neurogenesis and a depletion of hippocampal neural precursor cells (NPCs). This effect was attenuated by pretreatment with RSV. Furthermore, EtOH exposure resulted in a reduction in spine density on the granular neurons of the dentate gyrus (DG), and the spines exhibited a less mature morphological phenotype characterized by a higher proportion of stubby spines and a lower proportion of mushroom spines. However, RSV treatment effectively reversed these responses. We further confirmed that RSV treatment reversed the EtOH-induced down-regulation of hippocampal pERK and Hes1 protein levels, which may be related to the proliferation and maintenance of NPCs. Furthermore, EtOH exposure in the C17.2 NPCs also diminished cell proliferation and activated apoptosis, which could be reversed by pretreatment of RSV. Overall, our results suggest that RSV pretreatment protects against EtOH-induced defects in neurogenesis in postnatal mice and may thus play a critical role in preventing EtOH-mediated toxicity in the developing hippocampus.

  12. Postnatal development of tracheal surface epithelium and submucosal glands in the ferret.

    PubMed

    Leigh, M W; Gambling, T M; Carson, J L; Collier, A M; Wood, R E; Boat, T F

    1986-01-01

    We explored the usefulness of the postnatal ferret as a model for early developmental events in the large airways, using light and scanning electron microscopy. In the first 28 postnatal days, ferret tracheal surface epithelium and glands undergo dramatic growth and development. Tracheal surface area increases 8-fold. At birth, ciliated cells are sparse (9.4 +/- 1.2% of total epithelial cells). A significant increase in ciliated cells is observed at weekly intervals and by day 28 the ciliated cell is the predominant cell type (54.2 +/- 2.8% of total epithelial cells). Secretory cells decrease from 66.4 +/- 1.0% at birth to 22.2 +/- 2.8% of total epithelial cells. Histochemical staining of the granules of the epithelial secretory cells changes from predominantly non-acidic (staining with PAS but not Alcian blue) to predominantly acidic (staining also with Alcian blue). During the same time interval, tracheal glands develop from intraepithelial cellular aggregates devoid of secretory granules at birth into complex, submucosal tubuloacinar structures composed predominantly of cells containing non-acidic secretory granules at 28 days. Therefore, infant ferrets offer an opportunity to examine the structural and functional components of the mucociliary clearance mechanism at developmental stages which occur prenatally in many laboratory animals and in humans.

  13. [Influence of high concentration of antibodies to NGF during early embryogenesis on formation of mice behavior in postnatal period].

    PubMed

    Rodionov, A N; Lobanov, A V; Morozov, S G; Sidiakin, A A; Anikina, O M; Gribova, I E; Rybakov, A S; Protsenko, A N; Murashev, A N; Kliushnik, T P

    2012-01-01

    In this work the influence of high concentration of antibodies to NGF on mouse's progeny has been investigated. During immunization with NGF the highest concentrations of antibodies were created in the first and third days of pregnancy (in different groups of animals). The dependence of abnormalities of mice postnatal development on level of antibodies to NGF at different stages of early embryogenesis has been established. Increasing of abnormalities in the formation of early behavioral acts and more clinically apparent anomalies in the somatic maturation in case of maximum of antibodies on day I of pregnancy has been showed. Immune responses to NGF during early embryogenesis of mice cause lag in the formation of behavioral acts. The latter are characterized by difficulties in sensor-motor coordination of the limbs and more clinically apparent in mice with a maximum of antibodies on day 1 of embryonic development. Infantilism in developing of contacts between progeny and mothers detected in mice with immune reactions may be a sign of serious mental dysontogenesis. The accelerated development of working memory established in mice with immune response to NGF requires further study of the development of cognitive abilities in these animals. The obtained results illustrate the important regulatory role of NGF at the early stages of development of the nervous system.

  14. Effects of synchronous and asynchronous embryo transfer on postnatal development, adult health, and behavior in mice.

    PubMed

    López-Cardona, Angela P; Fernández-González, Raúl; Pérez-Crespo, Miriam; Alén, Francisco; de Fonseca, Fernando Rodriguez; Orio, Laura; Gutierrez-Adan, Alfonso

    2015-10-01

    Asynchronous embryo transfer (ET) is a common assisted reproduction technique used in several species, but its biological effects on postnatal and early development remain unknown. The aim of this study was to determine whether asynchronous ET produces long-term effects in mice. Postnatal development, animal weight, systolic blood pressure (SBP), relative organ weight (liver, spleen, kidneys, heart, lungs, brain, and testicles), and behavior (assessed in open-field and elevated plus maze tests) were assessed in CD1 mice produced by different ET procedures: 1) the transfer of Day 3.5 (D3.5) blastocysts to the uterus (BL-UT); 2) the transfer of D3.5 blastocysts to the oviduct (BL-OV); or 3) the transfer of D0.5 zygotes to the oviduct (Z-OV). In vivo conceived animals served as controls (CT). The transfer of blastocysts to the uterus or zygotes to the oviduct was defined as synchronous, and transfer of blastocysts to the oviduct was defined as asynchronous. Both synchronous and asynchronous ET resulted in increased weight at birth that normalized thereafter with the exception of asynchronous ET females. In this group, female BL-OV, a clear lower body weight was recorded along postnatal life when compared with controls (P < 0.05). No effects on animal weight were produced during postnatal development in the synchronous ET groups (BL-UT, Z-OV, and CT). Both synchronous and asynchronous ET had impacts on adult (Wk 30) organ weight. SBP was modified in animals derived from blastocyst but not zygote ET. Effects on behavior (anxiety in the plus maze) were only detected in the BL-UT group (P < 0.05). Our findings indicate that zygotes are less sensitive than blastocysts to ET and that both synchronous and asynchronous blastocyst ET may have long-term consequences on health, with possible impacts on weight, arterial pressure, relative organ weight, and behavior. © 2015 by the Society for the Study of Reproduction, Inc.

  15. Post-natal development of amiloride sensitive sodium transport in pig distal colon.

    PubMed

    Cremaschi, D; Ferguson, D R; Hénin, S; James, P S; Meyer, G; Smith, M W

    1979-07-01

    1. Both electrophysiological properties and unidirectional Na and Cl fluxes have been determined across distal colons taken from pigs during early post-natal development. 2. The transmural potential difference (Vms) was 5 mV in the new-born and 10 mV in the 4 day old colon. The short circuit current (Scc) showed a three to sixfold increase during the first 10 days of post-natal life. The microvillar membrane potential (Vm) fell from about -45 mV in the new-born to -40 mV in the 4 day old colon. 3. Amiloride had no effect on Vms, Scc or Vm, measured in the new-born animal. It reduced Vms and Scc, caused a hyperpolarization of Vm and increased the microvillar membrane/basolateral membrane resistance ratio (Rm/Rs) in colons taken from older animals. 4. The Scc of distal colons taken from new-born and 1 day old pigs was only half that predicted from unidirectional measurements of Na flux. This discrepancy, which could not be completely accounted for by net CL absorption, disappeared in the older animals. 5. Net transport of Na doubled during the first 24 h of post-natal life. Part of this transport took place through an amiloride sensitive, non-electrogenic, pathway. 6. It is suggested that Na uses mainly a non-electrogenic pathway to cross the mucosa of the new-born pig. This pathway is replaced by an electrogenic amiloride sensitive mechanism in older animals. Aldosterone is thought to initiate these changes in Na tranport.

  16. Effects of prenatal morphine on hypothalamic metabolism of neurotransmitters and gonadal and adrenal activities, during the early postnatal period in the rat.

    PubMed

    Lesage, J; Bernet, F; Montel, V; Dupouy, J P

    1996-06-01

    It is noteworthy that exposure to opiates during fetal development results in permanent changes in adults related to morphological, behavioral and biochemical measures; however little is known concerning the effects of such drugs in early postnatal life. We investigated in newborn rats the effects of prenatal morphine-exposure on both-the hypothalamic metabolism of norepinephrine (NE), serotonin (5 HT) and neuropeptide Y (NPY)-the activity of the hypothalamo-pituitary gonadal and adrenal axes. In a previous study performed in newborns of untreated mothers, we reported some sex-dependent changes in the metabolism of NE, 5 HT and NPY in the hypothalamus and an early activation of the gonadostimulating function and of the corticostimulating one. In control newborns from saline-treated mothers, a slight increase in the hypothalamic metabolism of NE (males) and 5 HT (males and females) was observed and it was comparable in both sexes. On the other hand, the hypothalamic content of NPY was unaffected in early postnatal period in newborn males as well as in females. These changes observed on hypothalamic metabolisms are temporally correlated with the early postnatal activation of the corticostimulating function in neonates of both sexes and that of the gonadostimulating one, mainly in males. Prenatal morphine exposure altered the hypothalamic metabolism of 5 HT which was increased mainly in newborn females but did not affect either the metabolism of NE or the NPY content of the hypothalamus. The more drastic effect of the prenatal morphine treatment is the atrophy and hypoactivity of the adrenals in newborns of both sexes at birth time and during the early postnatal period. In contrast morphine did not impair postnatal surge of the plasma testosterone level in male pups as well as late and slight increase of plasma estradiol in female ones.

  17. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex.

    PubMed

    Ueno, Hiroshi; Suemitsu, Shunsuke; Matsumoto, Yosuke; Okamoto, Motoi

    2015-01-01

    Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

  18. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

    PubMed Central

    Ueno, Hiroshi; Suemitsu, Shunsuke; Matsumoto, Yosuke; Okamoto, Motoi

    2015-01-01

    Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity. PMID:26161272

  19. Early Postnatal Diets Affect the Bioregional Small Intestine Microbiome and Ileal Metabolome in Neonatal Pigs.

    PubMed

    Piccolo, Brian D; Mercer, Kelly E; Bhattacharyya, Sudeepa; Bowlin, Anne K; Saraf, Manish K; Pack, Lindsay; Chintapalli, Sree V; Shankar, Kartik; Adams, Sean H; Badger, Thomas M; Yeruva, Laxmi

    2017-08-01

    Background: Breastfeeding is known to be protective against gastrointestinal disorders and may modify gut development. Although the gut microbiome has been implicated, little is known about how early diet affects the small intestine microbiome.Objective: We hypothesized that disparate early diets would promote unique microbial profiles in the small intestines of neonatal pigs.Methods: Male and female 2-d-old White Dutch Landrace pigs were either sow fed or provided dairy (Similac Advance powder; Ross Products Abbott Laboratories) or soy (Enfamil Prosobee Lipil powder; Mead Johnson Nutritionals) infant formulas until day 21. Bacterial ecology was assessed in the contents of the small intestine through the use of 16S ribosomal RNA sequencing. α-Diversity, β-diversity, and differential abundances of operational taxonomic units were assessed by ANOVA, permutational ANOVA, and negative binomial regression, respectively. Ileum tissue metabolomics were measured by LC-mass spectrometry and assessed by weighted correlation network analysis.Results: Greater α-diversity was observed in the duodena of sow-fed compared with formula-fed neonatal pigs (P < 0.05). No differences were observed in the ilea. Firmicutes represented the most abundant phylum across all diets in duodena (78.8%, 80.1%, and 53.4% relative abundance in sow, dairy, and soy groups, respectively), followed by Proteobacteria in sow (12.2%) and dairy (12.4%) groups and Cyanobacteria in soy-fed (36.2%) pigs. In contrast to those in the duodenum, Proteobacteria was the dominant phylum in the ileum, with >60% relative abundance in all of the groups. In the duodenum, 77 genera were altered by diet, followed by 48 in the jejunum and 19 in the ileum. Metabolomics analyses revealed associations between ileum tissue metabolites (e.g., acylcarnitines, 3-aminoisobutyric acid) and diet-responsive microbial genera.Conclusions: These results indicate that the neonatal diet has regional effects on the small intestine

  20. Dye coupling and connexin expression by cortical radial glia in the early postnatal subventricular zone.

    PubMed

    Freitas, Andressa S; Xavier, Anna L R; Furtado, Carla M; Hedin-Pereira, Cecilia; Fróes, Maira M; Menezes, João R L

    2012-12-01

    In this study, we have analyzed the specific contribution of the cortical radial glia (RG) for gap junctional communication (GJC) within the postnatal subventricular zone (SVZ). To specifically target RG as source of dye-coupling in situ, we have developed a new technique that involves direct cell loading through the processes that reach the pial surface, with a mix of gap junction permeant (Lucifer yellow, LY) and nonpermeant (rhodamine-conjugated dextran 3 KDa, RD) fluorochromes, the latter used as a marker for direct loaded cells. Tissue sections were analyzed for identification of directly loaded (LY+RD+) and coupled cells (LY+RD-) in the SVZ. Directly loaded cells were restricted to the region underlying the pial loading surface area. Coupled cells were distributed in a bistratified manner, along the outer dorsal surface of the SVZ and aligning the ventricle, leaving the SVZ core relatively free. Blocking GJC prior to pial loading greatly reduced dye coupling. Phenotypic analysis indicated that coupling by RG excludes neuroblasts and is mostly restricted to cells of glial lineage. Notwithstanding, no corresponding restriction to specific cell phenotype was found for two connexin isotypes, Cx43 and Cx45, in the postnatal SVZ. The extensive homocellular cell coupling by RG suggests an important role in the regulation of neurogenesis and functional compartmentalization of the postnatal SVZ.

  1. Valproic Acid Exposure during Early Postnatal Gliogenesis Leads to Autistic-like Behaviors in Rats

    PubMed Central

    Mony, Tamanna Jahan; Lee, Jae Won; Dreyfus, Cheryl; DiCicco-Bloom, Emanuel; Lee, Hee Jae

    2016-01-01

    Objective We reported that postnatal exposure of rats to valproic acid (VPA) stimulated proliferation of glial precursors during cortical gliogenesis. However, there are no reports whether enhanced postnatal gliogenesis affects behaviors related to neuropsychiatric disorders. Methods After VPA treatment during the postnatal day (PND) 2 to PND 4, four behavioral test, such as open field locomotor test, elevated plus maze test, three-chamber social interaction test, and passive avoidance test, were performed at PND 21 or 22. Results VPA treated rats showed significant hyperactive behavior in the open field locomotor test (p<0.05). Moreover, the velocity of movement in the VPA group was increased by 69.5% (p<0.01). In the elevated plus maze test, VPA exposed rats expressed significantly lower percentage of time spent on and of entries into open arms more than the control group (p<0.05). Also, both sociability and social preference indices with strangers in the three-chamber social interaction test were significantly lower in the VPA exposed rats (p<0.05). Conclusion Our results suggest that altered glial cell development is another locus at which pathogenetic factors can operate to contribute to the neurodevelopmental disorder. PMID:27776385

  2. Effect of low-level prenatal X-irradiation on postnatal development in the Wistar rat

    SciTech Connect

    Jensh, R.P.; Brent, R.L.

    1987-03-01

    The objective of this investigation was to determine the effect of low-dose prenatal X-irradiation on postnatal growth and neurobehavioral development, and whether alterations would manifest at dosages lower than those which produce anatomic malformations from exposure at the most sensitive period of organogenesis. Ninety-eight Wistar strain rats were exposed to 0.1, 0.2, or 0.4 Gy X-radiation of were sham irradiated on the 9th or 17th day of gestation. A conventional teratologic evaluation was completed on half of the animals (572 fetuses). The age of appearance of four physiologic markers and of acquisition of six reflexes was observed in 372 offspring. Exposure during early organogenesis at these levels had no effect on any of these parameters. Prenatal exposure to X-radiation on the 17th day of gestation at dosage levels greater than 0.1 Gy resulted in alterations in the appearance of three postnatal neurophysiologic parameters. Growth retardation throughout the postpartum period also was observed in the offspring. The induction of developmental and reflex alterations had a comparable threshold to the known threshold for anatomic malformations on the 9th day. These results indicate that all of the parameters studied had thresholds either at or above 0.2 Gy acute radiation, and that the postpartum developmental and reflex acquisition measures were not more sensitive indicators of exposure to X-radiation than growth parameters.

  3. Effects of age and biotin status on postnatal development of plasma biotinidase activity in rats.

    PubMed

    Heard, G S; Tanner, R W; Blevins, T L; Evans, J S; Redmond, J B; Roth, K S; Wolf, B

    1991-02-01

    Biotinidase activity was measured in plasmas of 1-, 7-, 14-, and 21-day-old rats from control dams and dams that had been fed a biotin-depleting diet from Day 15 of gestation. Biotinidase activity increased significantly in the plasma of rats from control and depleted mothers until Postnatal Day 14, after which there was a small but significant decline at Day 21. Differences between the mean activities of the two groups of pups on each sampling day were not significant and there were no significant differences in activity levels attributable to sex. Plasma albumin concentrations increased from birth until Day 21, and plasma biotinidase activity and albumin concentration were significantly correlated (r = +/- 0.43). We suggested that these two proteins may be controlled by a common mechanism in the early postnatal period, and that biotin deficiency does not affect the development of biotinidase activity. Because biotin-depleted neonatal pups show developmental changes in biotinidase activity similar to those of human newborns, and they can be produced reliably by depleting dams from Day 15 of gestation, they may be useful models for studying the developmental abnormalities associated with human biotinidase deficiency.

  4. Intrauterine growth and postnatal skeletal development: findings from the Southampton Women's Survey.

    PubMed

    Harvey, Nicholas C; Mahon, Pam A; Kim, Miranda; Cole, Zoe A; Robinson, Sian M; Javaid, Kassim; Inskip, Hazel M; Godfrey, Keith M; Dennison, Elaine M; Cooper, Cyrus

    2012-01-01

    We have previously demonstrated associations between fetal growth in late pregnancy and postnatal bone mass. However, the relationships between the intrauterine and early postnatal skeletal growth trajectory remain unknown. We addressed this in a large population-based mother-offspring cohort study. A total of 628 mother-offspring pairs were recruited from the Southampton Women's Survey. Fetal abdominal circumference was measured at 11, 19 and 34 weeks gestation using high-resolution ultrasound with femur length assessed at 19 and 34 weeks. Bone mineral content was measured postnatally in the offspring using dual-energy X-ray absorptiometry at birth and 4 years; postnatal linear growth was assessed at birth, 6, 12, 24, 36 and 48 months. Late pregnancy abdominal circumference growth (19-34 weeks) was strongly (P < 0.01) related to bone mass at birth, but less robustly associated with bone mass at 4 years. Early pregnancy growth (11-19 weeks) was more strongly related to bone mass at 4 years than at birth. Postnatal relationships between growth and skeletal indices at 4 years were stronger for the first and second postnatal years, than the period aged 2-4 years. The proportion of children changing their place in the distribution of growth velocities progressively reduced with each year of postnatal life. The late intrauterine growth trajectory is a better predictor of skeletal growth and mineralisation at birth, while the early intrauterine growth trajectory is a more powerful determinant of skeletal status at age 4 years. The perturbations in this trajectory which influence childhood bone mass warrant further research.

  5. Early postnatal skin colour changes in term newborns with subclinical histological chorioamnionitis.

    PubMed

    De Felice, Claudio; Vacca, Paola; Del Vecchio, Antonio; Criscuolo, Mario; Lozupone, Antonia; Latini, Giuseppe

    2004-09-01

    Chorioamnionitis, a known risk factor for fetal and neonatal morbidity both in preterm and term newborns, is often subclinical. Earlier observations have linked skin colourimetry to neonatal illness severity and adverse neonatal outcome. Here, we tested the hypothesis that subclinical histological chorioamnionitis is associated with early postnatal skin colour changes in term newborns. Skin colourimetry on ten body sites (forehead, cheek, forearm, palm, upper chest, abdomen, back, buttock, leg, and sole) was examined in 45 term infants with subclinical histological chorioamnionitis and 45 sex- and gestational age-matched controls, using a tristimulus portable colourimeter at 1, 5 and 10 min after birth. Infants with subclinical histological chorioamnionitis showed statistically significant early postnatal skin colourimetric differences, in nine and seven out of the ten body sites examined as compared to control newborns at 1 min (P< or =0.0092), 5 min (P< or =0.0081) and 10 min (P< or =0.0056) from birth, respectively. Skin colourimetry changes were associated with lower 1 min Apgar scores (P<0.0001), cord blood pH (P<0.0001), PaO2 (P<0.0001), and base excess (P<0.0001) values, together with higher cord blood PaCO2 (P=0.0001), NICU admissions (P=0.00076), endotracheal intubation in the delivery room (P=0.012), Neonatal Acute Physiology-Perinatal Extension (P<0.0001) and Neonatal Therapeutic Intervention Scoring System (P<0.0001) scores than the chorioamnionitis-negative infants. These findings, compatible with early peripheral microcirculatory changes, indicate skin vasoconstriction as an early neonatal manifestation of subclinical chorioamnionitis.

  6. Prenatal and early postnatal exposure to high-saturated-fat diet represses Wnt signaling and myogenic genes in offspring rats.

    PubMed

    Yang, Ke-Feng; Shen, Xiu-Hua; Cai, Wei

    2012-08-01

    The prenatal and early postnatal period is a key developmental window for nutrition status, and high-fat exposure in this period has been shown to be associated with type 2 diabetes, obesity and other features of metabolic disorders later in life. The present study was designed to investigate the underlying molecular mechanisms and role of relative genes involved in this process. We investigated the impact of prenatal and early postnatal exposure to a high-saturated-fat diet on the regulation of the Wnt signaling pathway and myogenic genes in skeletal muscle of rat offspring as well as the serum and muscle physiological outcomes. Timed-pregnant Sprague-Dawley rats were fed either a control (C, 16% kcal fat) or high-saturated-fat diet (HF, 45% kcal fat) throughout gestation and lactation. After weaning, female offspring were fed a control diet to generate two offspring groups: control diet-fed offspring of control diet-fed dams (C/C) and control diet-fed offspring of HF diet-fed dams (HF/C). The serum glucose of the HF/C offspring (5.58 ± 0.26 mmol/L) was significantly higher than that of C/C offspring (4.97 ± 0.28 mmol/L), and the Homeostasis Model Assessment-Insulin Resistance of HF/C offspring (2.00 ± 0.11) was also significantly higher when compared with C/C (1.84 ± 0.09). Furthermore, HF/C offspring presented excessive intramuscular fat accumulation (1.8-fold, P < 0.05) and decreased muscle glycogen (1.3-fold, P < 0.05), as well as impairment of muscle development at the age of 12 weeks. Meanwhile, we observed the repression of Wnt/β-catenin signaling and myogenic genes in HF/C offspring. The present study indicates that prenatal and early postnatal exposure to a high-saturated-fat diet suppresses the development of skeletal muscle and myogenic genes via Wnt/β-catenin signaling, and the inappropriate muscle development could potentially contribute to the predisposition of offspring to develop metabolic-syndrome-like phenotype in adulthood.

  7. Influences of prenatal and postnatal fraternity size on ovarian development in the mouse.

    PubMed

    Kirkpatrick, B W; Rutledge, J J

    1988-12-01

    An experiment was conducted to test effects of prenatal and postnatal fraternity size (size of litter in which an individual develops prenatally or is reared postnatally) on ovarian development in mice. Fraternity size treatments were created by standardizing sizes of prenatal and postnatal fraternities in which mice were gestated and reared. Prenatal fraternity size was standardized by surgery on Day 9 of gestation to 6, 10, and 14 fetuses. Postnatal fraternity size was standardized by randomly assigning pups to litters of 5, 10, or 15 pups within 24 h of birth. Female pups were killed at either 3 or 20 wk of age and right ovaries were prepared for histology. Follicles were classified by size and morphology, and numbers of follicles in each class were tabulated. Interaction of postnatal fraternity size and age was observed for number of antral follicles (p less than 0.05). Mice reared in small postnatal fraternities had more antral follicles at weaning (3 wk) and fewer antral follicles at maturity (20 wk of age) than mice reared in large postnatal fraternities. No effect of either prenatal or postnatal fraternity size on other follicle populations was observed (p greater than 0.20). Numbers of Type 2 (primordial), Type 3a, and Type 3b follicles changed with age (p less than 0.01); numbers of primordial follicles declined with age, but numbers of Type 3a and 3b follicles increased. A hypothesis of a negative association between postnatal fraternity size and number of antral follicles at 3 wk of age was supported, but a hypothesis of a positive association between fraternity size and number of primordial follicles was not supported.

  8. Early postnatal demoralisation among primiparous women in the community: measurement, prevalence and associated factors.

    PubMed

    Bobevski, Irene; Rowe, Heather; Clarke, David M; McKenzie, Dean P; Fisher, Jane

    2015-10-12

    Demoralisation is a psychological state occurring in stressful life situations where a person feels unable to respond effectively to their circumstances, characterised by feelings of distress, subjective incompetence, helplessness and hopelessness. The period after the birth of a first baby is a time of great changes and disruptions to many aspects of the mother's physical, psychological and social functioning. This can lead to feelings of distress, a sense of incompetence and helplessness. This study aimed to examine: (1) the psychometric properties of the Demoralisation Scale in a community setting; (2) the prevalence of demoralisation symptoms among primiparous women in the community; and (3) factors that are uniquely associated with demoralisation in the early postnatal period. Primiparous women attending community maternal health centres (n = 400) were recruited and administered the study's questionnaires through a telephone interview. The Demoralisation Scale was found to be a reliable and valid tool among women in the community who had recently given birth. Higher levels of demoralisation were independently associated with lower confidence on going home from the hospital after birth, lower rating of mother's self-rated global health, more than 3 h of infant crying and fussing in the last 24 h, and a controlling partner, after symptoms of depression and anxiety, and vulnerable personality characteristics were controlled for. The relevance of demoralisation to postnatal health practitioners in the community is in helping them to better understand women's experiences and to intervene in a way that is more meaningful and less stigmatising to women.

  9. Histamine reverses a memory deficit induced in rats by early postnatal maternal deprivation.

    PubMed

    Benetti, Fernando; da Silveira, Clarice Kras Borges; da Silva, Weber Cláudio; Cammarota, Martín; Izquierdo, Iván

    2012-01-01

    Early partial maternal deprivation causes long-lasting neurochemical, behavioral and brain structural effects. In rats, it causes a deficit in memory consolidation visible in adult life. Some of these deficits can be reversed by donepezil and galantamine, which suggests that they may result from an impairment of brain cholinergic transmission. One such deficit, representative of all others, is an impairment of memory consolidation, clearly observable in a one-trial inhibitory avoidance task. Recent data suggest a role of brain histaminergic systems in the regulation of behavior, particularly inhibitory avoidance learning. Here we investigate whether histamine itself, its analog SKF-91844, or various receptor-selective histamine agonists and antagonists given into the CA1 region of the hippocampus immediately post-training can affect retention of one-trial inhibitory avoidance in rats submitted to early postnatal maternal deprivation. We found that histamine, SKF-91844 and the H2 receptor agonist, dimaprit enhance consolidation on their own and reverse the consolidation deficit induced by maternal deprivation. The enhancing effect of histamine was blocked by the H2 receptor antagonist, ranitidine, but not by the H1 receptor antagonist pyrilamine or by the H3 antagonist thioperamide given into CA1 at doses known to have other behavioral actions, without altering locomotor and exploratory activity or the anxiety state of the animals. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may in part be due to an impairment of histamine mediated mechanisms in the CA1 region of the rat hippocampus.

  10. Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

    PubMed Central

    Benders, K. B.; Hunter, D. D.; Dey, R. D.

    2012-01-01

    Our recent study showed that prenatal and early postnatal exposure of mice to side-steam tobacco smoke (SS), a surrogate to environmental tobacco smoke (ETS), leads to increased airway responsiveness and sensory innervation later in life. However, the underlying mechanism initiated in early life that affects airway responses later in life remains undefined. The concomitant increase in nerve growth factor (NGF) after exposures suggests that NGF may be involved the regulation of airway innervation. Since NGF regulates sympathetic nerve responses, as well as sensory nerves, we extended previous studies by examining neuropeptide Y (NPY), a neuropeptide associated with sympathetic nerves. Different age groups of mice, postnatal day (PD) 2 and PD21, were exposed to either SS or filtered air (FA) for 10 consecutive days. The level of NPY protein in lung and the density of NPY nerve fibers in tracheal smooth muscle were significantly increased in the PD2–11SS exposure group compared with PD2–11FA exposure. At the same time, the level of NGF in lung tissue was significantly elevated in the PD2–11SS exposure groups. However, neither NPY (protein or nerves) nor NGF levels were significantly altered in PD21–30SS exposure group compared with the PD21–30FA exposure group. Furthermore, pretreatment with NGF antibody or K252a, which inhibits a key enzyme (tyrosine kinase) in the transduction pathway for NGF receptor binding, significantly diminished SS-enhanced NPY tracheal smooth muscle innervation and the increase in methacholine-induced airway resistance. These findings show that SS exposure in early life increases NPY tracheal innervation and alters pulmonary function and that these changes are mediated through the NGF. PMID:22003086

  11. Neuropeptide Y immunoreactive axons in the corpus callosum of the cat during postnatal development.

    PubMed

    Ding, S L; Elberger, A J

    1994-07-01

    Many immunocytochemical studies have identified different types of neurotransmitters localized in the corpus callosum (CC) axons in the adult mammal. Few studies have looked at the development of different neurochemically identified CC systems. Previous studies on the development of cat CC axons have indicated that a large number of transitory CC axons project to the cortex during early postnatal development. The present study focuses on the development of one neurochemically identified group of CC axons in the cat, labeled with an antibody against neuropeptide Y (NPY), to determine if this group participates in transitory CC axonal growth. Cats at specified ages from birth to adulthood were studied with a routine method of immunocytochemistry for antiserum to NPY. NPY-immunoreactive (ir) CC axons were detected at all stages examined, from newborn to adult; the peak density occurred during postnatal weeks (PNW) 3-4. During PNW 1-2, the density of NPY-ir CC axons increased gradually; some NPY-ir axons at this age had growth cones located within the CC bundle between the cerebral hemispheres. The density of the NPY-ir CC axons decreased gradually during PNW 5-7, and from PNW 8 to maturity only a few NPY-ir CC axons were observed. These results indicate that at least two types of NPY-ir CC axons (i.e., transitory and permanent) exist during development, and that most of these axons are eliminated or only express NPY-ir for a short period during development. The results also indicate that neurochemical subsets of CC axons participate in the extensive transitory growth observed by means of the membrane tracer DiI but they may follow unique developmental timetables.

  12. Embryonic and postnatal development of GABA, calbindin, calretinin, and parvalbumin in the mouse claustral complex.

    PubMed

    Dávila, José Carlos; Real, M Angeles; Olmos, Luis; Legaz, Isabel; Medina, Loreta; Guirado, Salvador

    2005-01-03

    We analyzed the development of immunoreactive expression patterns for the neurotransmitter gamma-aminobutyric acid (GABA) and the calcium-binding proteins calbindin, calretinin, and parvalbumin in the embryonic and postnatal mouse claustral complex. Each calcium-binding protein shows a different temporal and spatial pattern of development. Calbindin-positive cells start to be seen very early during embryogenesis and increase dramatically until birth, thus becoming the most abundant cell type during embryonic development, especially in the ventral pallial part of the claustrum. The distribution of calbindin neurons throughout the claustrum during embryonic development partly parallels that of GABA neurons, suggesting that at least part of the calbindin neurons of the claustral complex are GABAergic and originate in the subpallium. Parvalbumin cells, on the other hand, start to be seen only postnatally, and their number then increases while the density of calbindin neurons decreases. Based on calretinin expression in axons, the core/shell compartments of the dorsal claustrum start to be clearly seen at embryonic day 18.5 and may be related to the development of the thalamoclaustral input. Comparison with the expression of Cadherin 8, a marker of the developing dorsolateral claustrum, indicates that the core includes a central part of the dorsolateral claustrum, whereas the shell includes a peripheral area of the dorsolateral claustrum, plus the adjacent ventromedial claustrum. The present data on the spatiotemporal developmental patterns of several subtypes of GABAergic neurons in the claustral complex may help for future studies on temporal lobe epilepsies, which have been related to an alteration of the GABAergic activity.

  13. Anomalously high variation in postnatal development is ancestral for dinosaurs but lost in birds

    NASA Astrophysics Data System (ADS)

    Griffin, Christopher T.; Nesbitt, Sterling J.

    2016-12-01

    Compared with all other living reptiles, birds grow extremely fast and possess unusually low levels of intraspecific variation during postnatal development. It is now clear that birds inherited their high rates of growth from their dinosaurian ancestors, but the origin of the avian condition of low variation during development is poorly constrained. The most well-understood growth trajectories of later Mesozoic theropods (e.g., Tyrannosaurus, Allosaurus) show similarly low variation to birds, contrasting with higher variation in extant crocodylians. Here, we show that deep within Dinosauria, among the earliest-diverging dinosaurs, anomalously high intraspecific variation is widespread but then is lost in more derived theropods. This style of development is ancestral for dinosaurs and their closest relatives, and, surprisingly, this level of variation is far higher than in living crocodylians. Among early dinosaurs, this variation is widespread across Pangaea in the Triassic and Early Jurassic, and among early-diverging theropods (ceratosaurs), this variation is maintained for 165 million years to the end of the Cretaceous. Because the Late Triassic environment across Pangaea was volatile and heterogeneous, this variation may have contributed to the rise of dinosaurian dominance through the end of the Triassic Period.

  14. Anomalously high variation in postnatal development is ancestral for dinosaurs but lost in birds.

    PubMed

    Griffin, Christopher T; Nesbitt, Sterling J

    2016-12-20

    Compared with all other living reptiles, birds grow extremely fast and possess unusually low levels of intraspecific variation during postnatal development. It is now clear that birds inherited their high rates of growth from their dinosaurian ancestors, but the origin of the avian condition of low variation during development is poorly constrained. The most well-understood growth trajectories of later Mesozoic theropods (e.g., Tyrannosaurus, Allosaurus) show similarly low variation to birds, contrasting with higher variation in extant crocodylians. Here, we show that deep within Dinosauria, among the earliest-diverging dinosaurs, anomalously high intraspecific variation is widespread but then is lost in more derived theropods. This style of development is ancestral for dinosaurs and their closest relatives, and, surprisingly, this level of variation is far higher than in living crocodylians. Among early dinosaurs, this variation is widespread across Pangaea in the Triassic and Early Jurassic, and among early-diverging theropods (ceratosaurs), this variation is maintained for 165 million years to the end of the Cretaceous. Because the Late Triassic environment across Pangaea was volatile and heterogeneous, this variation may have contributed to the rise of dinosaurian dominance through the end of the Triassic Period.

  15. Intervention among new parents followed up by an interview study exploring their experiences of telemedicine after early postnatal discharge.

    PubMed

    Danbjørg, D B; Wagner, L; Kristensen, B R; Clemensen, J

    2015-06-01

    a move towards earlier postnatal discharge raises the challenge of finding new ways to support families when they are discharged early after childbirth. to explore how postnatal parents experienced the use of telemedicine following early discharge from hospital (i.e. 24 hours after childbirth) by investigating if they consider that their postnatal needs are met, and whether or not they experience a sense of security and parental self-efficacy. intervention followed by a qualitative interview study. The intervention took place on a postnatal ward with approximately 1000 births a year. An app including chat, a knowledgebase and automated messages was trialled between postnatal parents at home and the hospital. Parents had access to the app for seven days after discharge. 42 new mothers were recruited from the postnatal ward in accordance with the inclusion criteria (i.e. discharged within 24 hours of childbirth). Both parents were invited for interview. 42 sets of parents participated in the trial, and 28 sets agreed to be interviewed. Interviews (n=28) were conducted with 27 mothers and 11 fathers. Parents were interviewed together in 10 cases, 17 mothers were interviewed alone, and one father was interviewed alone. The data analysis was inspired by systematic text condensation based on Giorgi׳s descriptive phenomenological method. parents were confident in use of the app, and did not experience any barriers in contacting the nurses via asynchronous communication. Parents received timely information and guidance by communicating online, and felt that their follow-up support needs were met. parents viewed the app as a lifeline, and saw it as a means of informing and guiding them following early discharge from hospital after childbirth. As such, this app shows potential for enhancing self-efficacy and postnatal sense of security. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Oral Prenatal and Postnatal Development Study of WR238605 Succinate in Rats. Volume 2 of 2

    DTIC Science & Technology

    1996-09-18

    washing on any cohabitation day) HT = Hematoma NP = Not pregnant |A = Decreased activity N-2 ORAL DRENATAL AND POSTNATAL DEVELOPMENT STUDY OF WR238605...N = Normal SP- = Sperm negative (i.e.. sperm not observed in the vaginal washing on any cohabitation day) HT = Hematoma NP = Not pregnant JA...washing on any cohabitation day) |A = NP = Not pregnant N-4 Palpated pregnant Normal • Hematoma i Decreased activity ORAL PRENATAL AND POSTNATAL

  17. Decrease and disappearance of intramural neurons in the rat bladder during post-natal development.

    PubMed

    Alian, M; Gabella, G

    1996-11-01

    While confirming previous results that the bladder of adult female rats is devoid of intramural neurons, we show that during postnatal development some intramural neurons are present. There is about 200 of them per bladder at birth, and their number progressively decreases during post-natal life. In this strain of rats some neurons are still present at 12 weeks of age, and in one animal (out of five) there were still 25 neurons at 20 weeks of age.

  18. The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.

    PubMed

    Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J; Zykovich, Artem; Coon, Steven L; Klein, David C; Rath, Martin F

    2015-01-01

    Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9(-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9(-/-) mutant mice appear normal, severe hydrocephalus develops in about 70% of the Lhx9(-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9(-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.

  19. [EXPRESSION OF SEROTONIN TRANSPORTER IN THE DORSAL RAPHE NUCLEUS DURING THE EARLY POSTNATAL PERIOD IN NORMAL STATE AND UNDER PRENATAL DEFICIENCY OF THE SEROTONERGIC SYSTEM IN RATS].

    PubMed

    Khozhai, L I

    2016-01-01

    The expression of the serotonin transport membrane protein (5-NTT) in the dorsal raphe nucleus (DNR) was investigated in laboratory Wistar rats during the early postnatal period. The results of the immunocytochemical study using primary antibodies--anti-Serotonin transporter antibody (AbCam, UK)--showed that during the first 3 postnatal weeks the intensity of 5-NTT expression in DNR of control animals changes. At the earliest postnatal times the main part of subnuclear neurons (dorsal, ventral and lateral ones) of the dorsal raphe nucleus (DNR-d, DNR-v, DNR-lat) was shown to intensely express 5-NTT. Sites of 5-NTT localization are found on the membrane surface of neuron bodies and processes in neuropile. The reduction in the number of neurons expressing 5-NTT and of its binding sites was observed on P10. At this time a redistribution of 5-NTT localization sites occurs: they are very few on neuron bodies and dendrites but are located rather densely on the plasma membrane of axons. The number of neurons expressing 5-NTT gradually increases with age and in neuropile the density of 5-NTT localization sites rises. It is shown that during the prenatal development the reduction of serotonin level in all parts of the DNR leads to a reduction in both the number of neurons expressing 5-NTT and sites of its localization in the early postnatal period, this trend continuing with age.

  20. Fgf10-positive cells represent a progenitor cell population during lung development and postnatally.

    PubMed

    El Agha, Elie; Herold, Susanne; Al Alam, Denise; Quantius, Jennifer; MacKenzie, BreAnne; Carraro, Gianni; Moiseenko, Alena; Chao, Cho-Ming; Minoo, Parviz; Seeger, Werner; Bellusci, Saverio

    2014-01-01

    The lung mesenchyme consists of a widely heterogeneous population of cells that play crucial roles during development and homeostasis after birth. These cells belong to myogenic, adipogenic, chondrogenic, neuronal and other lineages. Yet, no clear hierarchy for these lineages has been established. We have previously generated a novel Fgf10(iCre) knock-in mouse line that allows lineage tracing of Fgf10-positive cells during development and postnatally. Using these mice, we hereby demonstrate the presence of two waves of Fgf10 expression during embryonic lung development: the first wave, comprising Fgf10-positive cells residing in the submesothelial mesenchyme at early pseudoglandular stage (as well as their descendants); and the second wave, comprising Fgf10-positive cells from late pseudoglandular stage (as well as their descendants). Our lineage-tracing data reveal that the first wave contributes to the formation of parabronchial and vascular smooth muscle cells as well as lipofibroblasts at later developmental stages, whereas the second wave does not give rise to smooth muscle cells but to lipofibroblasts as well as an Nkx2.1(-) E-Cad(-) Epcam(+) Pro-Spc(+) lineage that requires further in-depth analysis. During alveologenesis, Fgf10-positive cells give rise to lipofibroblasts rather than alveolar myofibroblasts, and during adult life, a subpopulation of Fgf10-expressing cells represents a pool of resident mesenchymal stromal (stem) cells (MSCs) (Cd45(-) Cd31(-) Sca-1(+)). Taken together, we show for the first time that Fgf10-expressing cells represent a pool of mesenchymal progenitors in the embryonic and postnatal lung. Our findings suggest that Fgf10-positive cells could be useful for developing stem cell-based therapies for treating interstitial lung diseases.

  1. The influence of postnatal nutrition on reproductive tract and endometrial gland development in dairy calves.

    PubMed

    Wilson, Meghan L; McCoski, Sarah R; Geiger, Adam J; Akers, R Michael; Johnson, Sally E; Ealy, Alan D

    2017-02-01

    Uterine gland development occurs after birth in cattle and other mammals. The timeline of gland development has been described in various species, but little is known about how postnatal diet influences uterine gland development. This is especially concerning in dairy heifers, where a variety of milk replacer and whole milk nutrition options exist. Little work also exists in cattle to describe how early exposure to steroids influences reproductive tract and uterine gland development. The objective of this work was to determine the effects of early postnatal plane of nutrition and estrogen supplementation on uterine gland development in calves. In both studies, Holstein heifer calves were assigned to restricted milk replacer (R-MR) or enhanced milk replacer (EH-MR) diets. In study 1, calves (R-MR, n = 6; EH-MR, n = 5) were euthanized at 8 wk. In study 2, calves were weaned at 8 wk and administered estradiol (R-MR, n = 6; EH-MR, n = 6) or placebo (R-MR, n = 6; EH-MR, n = 5) for an additional 14 d before euthanasia. Average daily gain and final body weight was greater in both studies in heifers fed the enhanced diet. At 8 wk, EH-MR calves had a greater number of glands and a smaller average gland size, but total gland area was not different from the R-MR group. At 10 wk, uterine gland number and size were not affected by diet or estrogen. Expression profiles of several paracrine mediators of gland development were examined. Increases in transcript abundance for IGF1 and IGFBP3 and a decrease in abundance of WNT7A were detected in calves fed the enhanced diet at 8 wk of age. Plane of nutrition did not affect transcript profiles at 10 wk of age, but estradiol supplementation decreased MET and WNT7A transcript abundance. To conclude, heifer calves on a restricted diet exhibited a uterine morphology and transcript profile suggestive of delayed uterine gland development. These changes appear to be corrected by wk 10 of life. Also, this work provides evidence supporting the

  2. Antenatal Health Care and Postnatal Dental Check-Ups Prevent Early Childhood Caries.

    PubMed

    Nakai, Yukie; Mori, Yukako; Tamaoka, Izumi

    2016-12-01

    The first stage of early childhood caries (ECC) is infection by mutans streptococci, of which the primary infection source is the child's mother. Early intervention programs including antenatal and postnatal phases are effective for reducing ECC. This study was conducted to assess the respective effects of antenatal health care and postnatal care such as regular dental check-ups on reducing ECC among 3-year-old Japanese children. This nested case-control study of 155 three-year-old children (49.0% boys) was conducted at a dental clinic that provides collaborative health services with the Obstetrics and Gynecology Clinic, Okayama. Child characteristics and the mothers' antenatal data were collected retrospectively from the dental charts. They were divided into two groups: caries-free children (n = 77) and children without ECC (n = 78). Most of the children (81.9%) received regular check-ups with topical fluoride application. Most of the mothers reported morning sickness during pregnancy (81.3%), normal delivery (72.9%), and used antenatal health care (80.6%). Over half (55.5%) were primigravida. Adjusted odds ratio (AOR) and 95% confidential interval (95% CI) were computed to assess the strength of association using logistic regression analysis. Receiving antenatal health care (AOR, 3.27; 95% CI, 1.30-8.24) and child's having regular check-ups (AOR, 3.42; 95% CI, 1.35-8.69) were significantly associated with caries-free status among three-year old children. For ECC prevention, antenatal health care is as effective as regular check-ups up to three years of age. The results of this retrospective study demonstrate that maternal health education during pregnancy is effective for ECC prevention.

  3. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney

    PubMed Central

    Albertoni Borghese, María F.; Ortiz, María C.; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P.

    2016-01-01

    Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth. PMID:26872270

  4. Animal model of autism using GSTM1 knockout mice and early post-natal sodium valproate treatment.

    PubMed

    Yochum, Carrie L; Bhattacharya, Prianka; Patti, Laryssa; Mirochnitchenko, Oleg; Wagner, George C

    2010-07-11

    Autism is a heterogeneous, behaviorally defined developmental disorder with unknown etiology but thought to be the result of environmental insult acting upon the developing brain of a genetically susceptible individual. Approximately 30% of individuals with autism have normal development up to the age of about 30 months after which they experience behavioral regression and lose previously acquired motor, cognitive and social skills. Early post-natal toxicant administration to mice has been used to model autistic regression. To test the hypothesis that genetically altered mice might be more sensitive to toxicant exposure early in life, mice with a deletion of glutathione-S-transferaseM1 (GSTM1; a gene associated with increased risk of autism that codes for an enzyme involved in the management of toxicant-induced oxidative stress) and wild-type controls were exposed to valproic acid (VPA; a toxicant known to cause autism-like behavioral deficits that, in part, are mediated through oxidative stress) on post-natal day 14. VPA treatment caused significant increases in apoptosis in granule cells of the hippocampus and cerebellum. There was a genotype by treatment by sex interaction with wild-type females exhibiting significantly fewer apoptotic cells in these regions compared to all other groups. VPA treatment also resulted in long-lasting deficits in social behaviors and significant alterations in brain chemistry. VPA-treated GSTM1 knockout animals performed significantly fewer crawl-under behaviors compared to saline-treated knockout animals as well as wild-type controls receiving either treatment. Collectively, these studies indicate that VPA-treatment causes cerebellar and hippocampal apoptosis and that having the wild-type GSTM1 genotype may confer protection against VPA-induced neuronal death in female mice. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Food, growth and time: Elsie Widdowson's and Robert McCance's research into prenatal and early postnatal growth.

    PubMed

    Buklijas, Tatjana

    2014-09-01

    Cambridge scientists Robert McCance and Elsie Widdowson are best known for their work on the British food tables and wartime food rations, but it is their research on prenatal and early postnatal growth that is today seen as a foundation of the fields studying the impact of environment upon prenatal development and, consequently, adult disease. In this essay I situate McCance's and Widdowson's 1940s human and 1950s experimental studies in the context of pre-war concerns with fetal growth and development, especially within biochemistry, physiology and agriculture; and the Second World War and post-war focus on the effects of undernutrition during pregnancy upon the fetus. I relate Widdowson's and McCance's research on the long-term effects of early undernutrition to the concern with recovery from early trauma so pertinent in post-war Europe and with sensitive (critical) periods, a concept of high importance across different fields. Finally I discuss how, following a hiatus in which fetal physiology engaged with different questions and stressed fetal autonomy, interest in the impact of environment upon prenatal growth and development revived towards the end of the twentieth century. The new field of "developmental origins of health and disease", I suggest, has provided a context in which Widdowson's and McCance's work has regained importance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Cellular composition characterizing postnatal development and maturation of the mouse brain and spinal cord.

    PubMed

    Fu, YuHong; Rusznák, Zoltán; Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

    2013-09-01

    The process of development, maturation, and regression in the central nervous system (CNS) are genetically programmed and influenced by environment. Hitherto, most research efforts have focused on either the early development of the CNS or the late changes associated with aging, whereas an important period corresponding to adolescence has been overlooked. In this study, we searched for age-dependent changes in the number of cells that compose the CNS (divided into isocortex, hippocampus, olfactory bulb, cerebellum, 'rest of the brain', and spinal cord) and the pituitary gland in 4-40-week-old C57BL6 mice, using the isotropic fractionator method in combination with neuronal nuclear protein as a marker for neuronal cells. We found that all CNS structures, except for the isocortex, increased in mass in the period of 4-15 weeks. Over the same period, the absolute number of neurons significantly increased in the olfactory bulb and cerebellum while non-neuronal cell numbers increased in the 'rest of the brain' and isocortex. Along with the gain in body length and weight, the pituitary gland also increased in mass and cell number, the latter correlating well with changes of the brain and spinal cord mass. The majority of the age-dependent alterations (e.g., somatic parameters, relative brain mass, number of pituitary cells, and cellular composition of the cerebellum, isocortex, rest of the brain, and spinal cord) occur rapidly between the 4th and 11th postnatal weeks. This period includes murine adolescence, underscoring the significance of this stage in the postnatal development of the mouse CNS.

  7. Maternal perinatal undernutrition alters postnatal development of chromaffin cells in the male rat adrenal medulla.

    PubMed

    Molendi-Coste, Olivier; Laborie, Christine; Scarpa, Maria Cristina; Montel, Valérie; Vieau, Didier; Breton, Christophe

    2009-01-01

    Numerous data suggest that the development of the sympathoadrenal system is highly sensitive to the perinatal environment. We previously reported that maternal perinatal food restriction by 50% (FR50) altered chromaffin cell (CC) organization and activity in offspring at weaning. This study investigated the effects of FR50 on the postnatal time course of CC functional and structural adaptations. FR50 pups exhibited smaller and more abundant scattered clusters of noradrenergic CCs as early as postnatal day 7 (P7), indicating that morphological changes took place earlier during development. At birth, the adrenaline release was defective in FR50 pups, suggesting that maternal FR50 impaired the non-neurogenic control of catecholamine release. At P4, the catecholamine release in response to insulin-induced hypoglycaemia was also absent in FR50 pups. This was associated with the reduction of adrenal catecholamine contents, indicating that the failure to synthesize catecholamine might lead to impaired secretion. We hypothesized that maternal FR50 accelerated the functional connections between CCs and splanchnic nerve endings, leading to the premature loss of the non-neurogenic response. Acetylcholine-containing synaptic endings seemed more precociously functional in FR50 pups, as suggested by increased levels of acetylcholine esterase activity at P14. At P7, insulin-induced hypoglycaemia caused preferential adrenaline release associated with increased catecholamine contents in both groups. However, the response was accentuated in FR50 pups. At P14, the insulin challenge increased plasma levels of adrenaline in control rats, whereas it markedly enhanced the circulating level of both catecholamines in FR50 pups. We demonstrated that maternal FR50 leads to developmentally impaired noradrenergic CC aggregation and advanced splanchnic neurotransmission maturation associated with altered medulla activity in response to metabolic stress. This might contribute to the long

  8. Epigenetics of Early Child Development

    PubMed Central

    Murgatroyd, Chris; Spengler, Dietmar

    2011-01-01

    Comprehensive clinical studies show that adverse conditions in early life can severely impact the developing brain and increase vulnerability to mood disorders later in life. During early postnatal life the brain exhibits high plasticity which allows environmental signals to alter the trajectories of rapidly developing circuits. Adversity in early life is able to shape the experience-dependent maturation of stress-regulating pathways underlying emotional functions and endocrine responses to stress, such as the hypothalamo–pituitary–adrenal (HPA) system, leading to long-lasting altered stress responsivity during adulthood. To date, the study of gene–environment interactions in the human population has been dominated by epidemiology. However, recent research in the neuroscience field is now advancing clinical studies by addressing specifically the mechanisms by which gene–environment interactions can predispose individuals toward psychopathology. To this end, appropriate animal models are being developed in which early environmental factors can be manipulated in a controlled manner. Here we will review recent studies performed with the common aim of understanding the effects of the early environment in shaping brain development and discuss the newly developing role of epigenetic mechanisms in translating early life conditions into long-lasting changes in gene expression underpinning brain functions. Particularly, we argue that epigenetic mechanisms can mediate the gene–environment dialog in early life and give rise to persistent epigenetic programming of adult physiology and dysfunction eventually resulting in disease. Understanding how early life experiences can give rise to lasting epigenetic marks conferring increased risk for mental disorders, how they are maintained and how they could be reversed, is increasingly becoming a focus of modern psychiatry and should pave new guidelines for timely therapeutic interventions. PMID:21647402

  9. Fetal and post-natal lung defects reveal a novel and required role for Fgf8 in lung development

    PubMed Central

    Yu, Shibin; Poe, Bryan; Schwarz, Margaret; Elliot, Sarah; Albertine, Kurt H.; Fenton, Stephen; Garg, Vidu; Moon, Anne M.

    2016-01-01

    The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound. PMID:20727874

  10. Fetal and postnatal lung defects reveal a novel and required role for Fgf8 in lung development.

    PubMed

    Yu, Shibin; Poe, Bryan; Schwarz, Margaret; Elliot, Sarah A; Albertine, Kurt H; Fenton, Stephen; Garg, Vidu; Moon, Anne M

    2010-11-01

    The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long-term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Synergistic effects of prenatal hypoxia and postnatal high-fat diet in the development of cardiovascular pathology in young rats.

    PubMed

    Rueda-Clausen, Christian F; Morton, Jude S; Dolinsky, Vernon W; Dyck, Jason R B; Davidge, Sandra T

    2012-08-15

    We have previously shown that adult offspring exposed to a prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) are more susceptible to cardiovascular pathologies. Our objectives were to evaluate the interaction between hypoxia-induced IUGR and postnatal diet in the early development of cardiovascular pathologies. Furthermore, we sought to determine whether the postnatal administration of resveratrol could prevent the development of cardiovascular disorders associated with hypoxia-induced IUGR. On day 15 of pregnancy, Sprague-Dawley rats were randomly assigned to hypoxia (11.5% oxygen), to induce IUGR, or normal oxygen (control) groups. For study A, male offspring (3 wk of age) were randomly assigned a low-fat (LF, <10% fat) or a high-fat (HF, 45% fat) diet. For study B, offspring were randomized to either HF or HF+resveratrol diets. After 9 wk, cardiac and vascular functions were evaluated. Prenatal hypoxia and HF diet were associated with an increased myocardial susceptibility to ischemia. Blood pressure, in vivo cardiac function, and ex vivo vascular function were not different among experimental groups; however, hypoxia-induced IUGR offspring had lower resting heart rates. Our results suggest that prenatal insults can enhance the susceptibility to a second hit such as myocardial ischemia, and that this phenomenon is exacerbated, in the early stages of life by nutritional stressors such as a HF diet. Supplementing HF diets with resveratrol improved cardiac tolerance to ischemia in offspring born IUGR but not in controls. Thus we conclude that the additive effect of prenatal (hypoxia-induced IUGR) and postnatal (HF diet) factors can lead to the earlier development of cardiovascular pathology in rats, and postnatal resveratrol supplementation prevented the deleterious cardiovascular effects of HF diet in offspring exposed to prenatal hypoxia.

  12. Immune cell location and function during post-natal mammary gland development.

    PubMed

    Reed, Johanna R; Schwertfeger, Kathryn L

    2010-09-01

    Post-natal mammary gland development requires complex interactions between the epithelial cells and various cell types within the stroma. Recent studies have illustrated the importance of immune cells and their mediators during the various stages of mammary gland development. However, the mechanisms by which these immune cells functionally contribute to mammary gland development are only beginning to be understood. This review provides an overview of the localization of immune cells within the mammary gland during the various stages of post-natal mammary gland development. Furthermore, recent studies are summarized that illustrate the mechanisms by which these cells are recruited to the mammary gland and their functional roles in mammary gland development.

  13. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    PubMed

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

  14. Enriched environment has limited capacity for the correction of hippocampal memory-dependent schizoid behaviors in rats with early postnatal NMDAR dysfunction.

    PubMed

    Melik, Enver; Babar, Emine; Kocahan, Sayad; Guven, Mustafa; Akillioglu, Kubra

    2014-04-01

    Pre- and early postnatal stress can cause dysfunction of the N-methyl-d-aspartate receptor (NMDAR) and thereby promote the development of hippocampus memory-dependent schizoid abnormalities of navigation in space, time, and knowledge. An enriched environment improves mental abilities in humans and animals. Whether an enriched environment can prevent the development of schizoid symptoms induced by neonatal NMDAR dysfunction was the central question of our paper. The experimental animals were Wistar rats. Early postnatal NMDAR dysfunction was created by systemic treatment of rat pups with the NMDAR antagonist MK-801 at PD10-20 days. During the development period (PD21-90 days), the rats were reared in cognitively and physically enriched cages. Adult age rats were tested on navigation based on pattern separation and episodic memory in the open field and on auto-hetero-associations based on episodic and semantic memory in a step-through passive avoidance task. The results showed that postnatal NMDAR antagonism caused abnormal behaviors in both tests. An enriched environment prevented deficits in the development of navigation in space based on pattern separation and hetero-associations based on semantic memory. However, an enriched environment was unable to rescue navigation in space and auto-associations based on episodic memory. These data may contribute to the understanding that an enriched environment has a limited capacity for therapeutic interventions in protecting the development of schizoid syndromes in children and adolescents. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. Analysis of gene–environment interactions in postnatal development of the mammalian intestine

    PubMed Central

    Rakoff-Nahoum, Seth; Kong, Yong; Kleinstein, Steven H.; Subramanian, Sathish; Ahern, Philip P.; Gordon, Jeffrey I.; Medzhitov, Ruslan

    2015-01-01

    Unlike mammalian embryogenesis, which takes place in the relatively predictable and stable environment of the uterus, postnatal development can be affected by a multitude of highly variable environmental factors, including diet, exposure to noxious substances, and microorganisms. Microbial colonization of the intestine is thought to play a particularly important role in postnatal development of the gastrointestinal, metabolic, and immune systems. Major changes in environmental exposure occur right after birth, upon weaning, and during pubertal maturation into adulthood. These transitions include dramatic changes in intestinal contents and require appropriate adaptations to meet changes in functional demands. Here, we attempt to both characterize and provide mechanistic insights into postnatal intestinal ontogeny. We investigated changes in global intestinal gene expression through postnatal developmental transitions. We report profound alterations in small and large intestinal transcriptional programs that accompany both weaning and puberty in WT mice. Using myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) double knockout littermates, we define the role of toll-like receptors (TLRs) and interleukin (IL)-1 receptor family member signaling in postnatal gene expression programs and select ontogeny-specific phenotypes, such as vascular and smooth muscle development and neonatal epithelial and mast cell homeostasis. Metaanalysis of the effect of the microbiota on intestinal gene expression allowed for mechanistic classification of developmentally regulated genes by TLR/IL-1R (TIR) signaling and/or indigenous microbes. We find that practically every aspect of intestinal physiology is affected by postnatal transitions. Developmental timing, microbial colonization, and TIR signaling seem to play distinct and specific roles in regulation of gene-expression programs throughout postnatal development. PMID:25691701

  16. Analysis of gene-environment interactions in postnatal development of the mammalian intestine.

    PubMed

    Rakoff-Nahoum, Seth; Kong, Yong; Kleinstein, Steven H; Subramanian, Sathish; Ahern, Philip P; Gordon, Jeffrey I; Medzhitov, Ruslan

    2015-02-17

    Unlike mammalian embryogenesis, which takes place in the relatively predictable and stable environment of the uterus, postnatal development can be affected by a multitude of highly variable environmental factors, including diet, exposure to noxious substances, and microorganisms. Microbial colonization of the intestine is thought to play a particularly important role in postnatal development of the gastrointestinal, metabolic, and immune systems. Major changes in environmental exposure occur right after birth, upon weaning, and during pubertal maturation into adulthood. These transitions include dramatic changes in intestinal contents and require appropriate adaptations to meet changes in functional demands. Here, we attempt to both characterize and provide mechanistic insights into postnatal intestinal ontogeny. We investigated changes in global intestinal gene expression through postnatal developmental transitions. We report profound alterations in small and large intestinal transcriptional programs that accompany both weaning and puberty in WT mice. Using myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) double knockout littermates, we define the role of toll-like receptors (TLRs) and interleukin (IL)-1 receptor family member signaling in postnatal gene expression programs and select ontogeny-specific phenotypes, such as vascular and smooth muscle development and neonatal epithelial and mast cell homeostasis. Metaanalysis of the effect of the microbiota on intestinal gene expression allowed for mechanistic classification of developmentally regulated genes by TLR/IL-1R (TIR) signaling and/or indigenous microbes. We find that practically every aspect of intestinal physiology is affected by postnatal transitions. Developmental timing, microbial colonization, and TIR signaling seem to play distinct and specific roles in regulation of gene-expression programs throughout postnatal development.

  17. Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology

    PubMed Central

    Elston, Guy N.; Fujita, Ichiro

    2014-01-01

    Here we review recent findings related to postnatal spinogenesis, dendritic and axon growth, pruning and electrophysiology of neocortical pyramidal cells in the developing primate brain. Pyramidal cells in sensory, association and executive cortex grow dendrites, spines and axons at different rates, and vary in the degree of pruning. Of particular note is the fact that pyramidal cells in primary visual area (V1) prune more spines than they grow during postnatal development, whereas those in inferotemporal (TEO and TE) and granular prefrontal cortex (gPFC; Brodmann's area 12) grow more than they prune. Moreover, pyramidal cells in TEO, TE and the gPFC continue to grow larger dendritic territories from birth into adulthood, replete with spines, whereas those in V1 become smaller during this time. The developmental profile of intrinsic axons also varies between cortical areas: those in V1, for example, undergo an early proliferation followed by pruning and local consolidation into adulthood, whereas those in area TE tend to establish their territory and consolidate it into adulthood with little pruning. We correlate the anatomical findings with the electrophysiological properties of cells in the different cortical areas, including membrane time constant, depolarizing sag, duration of individual action potentials, and spike-frequency adaptation. All of the electrophysiological variables ramped up before 7 months of age in V1, but continued to ramp up over a protracted period of time in area TE. These data suggest that the anatomical and electrophysiological profiles of pyramidal cells vary among cortical areas at birth, and continue to diverge into adulthood. Moreover, the data reveal that the “use it or lose it” notion of synaptic reinforcement may speak to only part of the story, “use it but you still might lose it” may be just as prevalent in the cerebral cortex. PMID:25161611

  18. CD44 is a marker for the outer pillar cells in the early postnatal mouse inner ear.

    PubMed

    Hertzano, Ronna; Puligilla, Chandrakala; Chan, Siaw-Lin; Timothy, Caroline; Depireux, Didier A; Ahmed, Zubair; Wolf, Jeffrey; Eisenman, David J; Friedman, Thomas B; Riazuddin, Sheikh; Kelley, Matthew W; Strome, Scott E

    2010-09-01

    Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters' cells in the Fgfr3 ( P244R/ ) (+) mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells.

  19. Impact of birth weight and gender on early postnatal hypothalamic energy balance regulatory gene expression in the young lamb.

    PubMed

    Adam, C L; Bake, T; Findlay, P A; Milne, J S; Aitken, R P; Wallace, J M

    2013-11-01

    Intra-uterine growth restriction (IUGR) is involved in developmental metabolic programming and here we test the hypothesis that IUGR affects the developing hypothalamic energy balance regulatory pathways in a sex-specific manner. This experiment investigated early postnatal hypothalamic gene expression for six primary leptin- and insulin-sensitive neuropeptides and receptors in male and female IUGR (n = 8 and 9, respectively) and normal (N) birth weight lambs (n = 8 per gender) gestated and suckled by overnourished mothers. IUGR lambs were smaller at birth, had increased fractional growth rates (FGR), lower final body weight (11 weeks) and similar body fat content compared with N lambs, while males had higher final body weight and insulinemia but lower body fat and leptinemia than females. In situ hybridization revealed greater gene expression in the hypothalamic arcuate nucleus at 11 weeks for anorexigenic genes in females and orexigenic genes in males, with no effect of IUGR. Leptinemia correlated with gene expression for neuropeptide Y (NPY, negatively) in both sexes and pro-opiomelanocortin (POMC, positively) in females but with leptin receptor (negatively) only in males. Current FGR for girth correlated negatively with gene expression for NPY in males and POMC in females. Neither IUGR nor gender affected suckling activity (proxy for appetite) assessed at 3 weeks, but final NPY gene expression correlated with suckling weight gain in males. This study has revealed no effect of IUGR on early postnatal hypothalamic energy balance gene expression but a major effect of gender associated with major sex differences in adiposity and leptinemia. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  20. Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

    PubMed Central

    Murphy, Michelle C.; Fox, Edward A.

    2007-01-01

    The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

  1. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period

    PubMed Central

    Tooher, Rebecca; Gates, Simon; Dowswell, Therese; Davis, Lucy-Jane

    2014-01-01

    significant findings in this review are largely derived from trials which are not of high methodological quality. It was not possible to assess the effects of any of these interventions on most outcomes, and especially on rare outcomes such as death, TED and osteoporosis, because of small sample sizes and the small number of trials making the same comparisons.There was some evidence of side effects associated with thromboprophylaxis. Authors’ conclusions There is insufficient evidence on which to base recommendations for thromboprophylaxis during pregnancy and the early postnatal period. Large scale randomised trials of currently-used interventions should be conducted. PMID:20464719

  2. Early postnatal lethality and cardiovascular defects in CXCR7-deficient mice.

    PubMed

    Gerrits, Han; van Ingen Schenau, Dorette S; Bakker, Nicole E C; van Disseldorp, Ad J M; Strik, Ankie; Hermens, Laura S; Koenen, Tim B; Krajnc-Franken, Magda A M; Gossen, Jan A

    2008-05-01

    CXCR7 is a G-protein coupled receptor that was recently deorphanized and shown to have SDF1 and I-TAC as high affinity ligands. Here we describe the characterization of CXCR7-deficient mice that were generated to further investigate the function of this receptor in vivo. Expression analysis using a LacZ reporter knockin revealed that postnatally Cxcr7 was specifically expressed in cardiomyocytes, vascular endothelial cells of the lung and heart, the cerebral cortex and in osteocytes of the bone. Adult tissues revealed high expression in cardiomyocytes and osteocytes. The observation that 70% of the Cxcr7-/- mice died in the first week after birth coincides with expression of Cxcr7 in vascular endothelial cells and in cardiomyocytes. An important role of CXCR7 in the cardiovascular system was further supported by the observation that hearts of the Cxcr7-/- mice were enlarged, showed myocardial degeneration and fibrosis of postnatal origin, and hyperplasia of embryonic origin. Despite high expression in osteocytes no apparent bone phenotype was observed, neither in combination with ovariectomy nor orchidectomy. Thus as CXCR7 does not seem to play an important role in bone our data indicate an important function of CXCR7 in the cardiovascular system during multiple steps of development.

  3. Postnatal brain development: Structural imaging of dynamic neurodevelopmental processes

    PubMed Central

    Jernigan, Terry L.; Baaré, William F. C.; Stiles, Joan; Madsen, Kathrine Skak

    2013-01-01

    After birth, there is striking biological and functional development of the brain’s fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain–behavior associations in children, including genetic variation, behavioral interventions, and hormonal variation associated with puberty. At present longitudinal studies are few, and we do not yet know how variability in individual trajectories of biological development in specific neural systems map onto similar variability in behavioral trajectories. PMID:21489384

  4. Postnatal development of noradrenergic terminals in the rat trigeminal motor nucleus: A light and electron microscopic immunocytochemical analysis.

    PubMed

    Min, Ming-Yuan; Hsu, Pei-Cheng; Lu, Hsin-Wei; Lin, Chia-Jin; Yang, Hsiu-Wen

    2007-01-01

    The noradrenergic (NA) innervation in the trigeminal motor nucleus (Vmot) of postnatal and adult rats was examined by light and electron microscopic immunocytochemistry using antibodies against dopamine-beta-hydroxylase or tyrosine hydroxylase. NA fibers were identified in the Vmot as early as the day of birth (postnatal day 0; P0). A continuous increase in the density of labeled fibers was observed during development up to P20, with a slight decrease at P30 and in the adult. Electron microscopic analysis of serial ultrathin sections revealed that, at P5, nearly half (46%) of the examined NA terminals made synaptic contact with other neuronal elements with membrane specializations. The percentage of examined NA varicosities engaged in synaptic contacts increased at P15 (74%), then decreased in the adult (64%). At all developmental ages, the majority of contacts made by these boutons were symmetrical, the postsynaptic elements being mainly dendrites and occasionally somata. Interestingly, some of the NA terminals made axo-axon contacts with other unidentified boutons. These results show that, although the density of NA fibers increases during postnatal development, functional NA boutons are present in the Vmot at early postnatal ages. Some of these fibers might exert their effects via nonsynaptic release of noradrenaline, the so-called volume transmission, but, in the main, they form conventional synaptic contacts with dendrites, somata, and other axonal terminals in the Vmot. These results are consistent with previous electrophysiological studies that propose an important role for the NA system in modulating mastication. c 2006 Wiley-Liss, Inc.

  5. Pre- and postnatal arsenic exposure and child development at 18 months of age: a cohort study in rural Bangladesh.

    PubMed

    Hamadani, Jena D; Grantham-McGregor, Sally M; Tofail, Fahmida; Nermell, Barbro; Fängström, Britta; Huda, Syed N; Yesmin, Sakila; Rahman, Mahfuzar; Vera-Hernández, Marcos; Arifeen, Shams E; Vahter, Marie

    2010-10-01

    Exposure to arsenic through drinking water has been associated with impaired cognitive function in school-aged children in cross-sectional studies; however, there are few longitudinal studies and little information on effects of exposure in early life when the brain is generally most vulnerable. A longitudinal cohort study beginning in early pregnancy was conducted in rural Bangladesh, where arsenic concentrations in well water vary considerably. We assessed the effects of pre- and postnatal arsenic exposure on development of 2112 children at 18 months of age with Bayley Scales of Infant Development-II (mental and psychomotor development indices), Wolke's Behavior Rating Scale and maternal report of language. We related the measures of child development to arsenic concentrations in maternal urine in gestational weeks 9 and 30 and child's urinary arsenic at 18 months of age. Details of socio-economic background, home stimulation and anthropometric measurements of mothers and children were also available. Median maternal urinary arsenic concentration averaged over early and late gestation was 96 µg/l, whereas children's urine contained 35 µg/l of arsenic. There was no significant effect of any of the arsenic exposure measures on any of the child development measures after controlling for social and economic confounders, child's age and sex. Contrary to expectations, we found no indications of adverse effects of pre- or postnatal arsenic exposure on child development at 18 months. It remains possible that duration of exposure is critical and that effects will become apparent later in childhood.

  6. Reelin, an extracellular matrix protein linked to early onset psychiatric diseases, drives postnatal development of the prefrontal cortex via GluN2B-NMDARs and the mTOR pathway.

    PubMed

    Iafrati, J; Orejarena, M J; Lassalle, O; Bouamrane, L; Gonzalez-Campo, C; Chavis, P

    2014-04-01

    Defective brain extracellular matrix (ECM) is a factor of vulnerability in various psychiatric diseases such as schizophrenia, depression and autism. The glycoprotein reelin is an essential building block of the brain ECM that modulates neuronal development and participates to the functions of adult central synapses. The reelin gene (RELN) is a strong candidate in psychiatric diseases of early onset, but its synaptic and behavioral functions in juvenile brain circuits remain unresolved. Here, we found that in juvenile reelin-haploinsufficient heterozygous reeler mice (HRM), abnormal fear memory erasure is concomitant to reduced dendritic spine density and anomalous long-term potentiation in the prefrontal cortex. In juvenile HRM, a single in vivo injection with ketamine or Ro25-6981 to inhibit GluN2B-N-methyl-D-aspartate receptors (NMDARs) restored normal spine density, synaptic plasticity and converted fear memory to an erasure-resilient state typical of adult rodents. The functional and behavioral rescue by ketamine was prevented by rapamycin, an inhibitor of the mammalian target of rapamycin pathway. Finally, we show that fear memory erasure persists until adolescence in HRM and that a single exposure to ketamine during the juvenile period reinstates normal fear memory in adolescent mice. Our results show that reelin is essential for successful structural, functional and behavioral development of juvenile prefrontal circuits and that this developmental period provides a critical window for therapeutic rehabilitation with GluN2B-NMDAR antagonists.

  7. Developing electrical properties of postnatal mouse lumbar motoneurons

    PubMed Central

    Durand, Jacques; Filipchuk, Anton; Pambo-Pambo, Arnaud; Amendola, Julien; Borisovna Kulagina, Iryna; Guéritaud, Jean-Patrick

    2015-01-01

    We studied the rapid changes in electrical properties of lumbar motoneurons between postnatal days 3 and 9 just before mice weight-bear and walk. The input conductance and rheobase significantly increased up to P8. A negative correlation exists between the input resistance (Rin) and rheobase. Both parameters are significantly correlated with the total dendritic surface area of motoneurons, the largest motoneurons having the lowest Rin and the highest rheobase. We classified the motoneurons into three groups according to their discharge firing patterns during current pulse injection (transient, delayed onset, sustained). The delayed onset firing type has the highest rheobase and the fastest action potential (AP) whereas the transient firing group has the lowest rheobase and the less mature AP. We found 32 and 10% of motoneurons with a transient firing at P3–P5 and P8, respectively. About 20% of motoneurons with delayed onset firing were detected at P8. At P9, all motoneurons exhibit a sustained firing. We defined five groups of motoneurons according to their discharge firing patterns in response to ascending and descending current ramps. In addition to the four classical types, we defined a fifth type called transient for the quasi-absence of discharge during the descending phase of the ramp. This transient type represents about 40% between P3–P5 and tends to disappear with age. Types 1 and 2 (linear and clockwise hysteresis) are the most preponderant at P6–P7. Types 3 and 4 (prolonged sustained and counter clockwise hysteresis) emerge at P8–P9. The emergence of types 3 and 4 probably depends on the maturation of L type calcium channels in the dendrites of motoneurons. No correlation was found between groups defined by step or triangular ramp of currents with the exception of transient firing patterns. Our data support the idea that a switch in the electrical properties of lumbar motoneurons might exist in the second postnatal week of life in mice. PMID

  8. Effects of Prenatal Irradiation with an Accelerated Heavy-Ion Beam on Postnatal Development in Rats

    NASA Astrophysics Data System (ADS)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Fujita, K.; Coffigny, H.; Hayata, I.

    Effects on postnatal neurophysiological development in offspring were studied following exposure of pregnant Wistar rats to accelerated neon-ion beams with a LET value of about 30 keV mu m at a dose range from 0 1 Gy to 2 0Gy on the 15th day of gestation The age at which four physiologic markers appeared and five reflexes were acquired was examined prior to weaning Gain in body weight was monitored until the offspring were 3 months old Male offspring were evaluated as young adults using two behavioral tests The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison Our previous study on carbon-ion beams with a LET value of about 13 keV mu m was also cited to elucidate a possible LET-related effect For most of the endpoints at early age significant alteration was even observed in offspring prenatally received 0 1 Gy of accelerated neon ions while neither X rays nor carbon-ions under the same dose resulted in such a significant alteration compared to that from the sham-irradiated dams All offspring whose mothers received 2 0 Gy died prior to weaning Offspring from dams irradiated with accelerated neon ions generally showed higher incidences of prenatal death and preweaning mortality markedly delayed accomplishment in their physiological markers and reflexes and gain in body weight compared to those exposed to X-rays or carbon ions at doses of 0 1 to 1 5 Gy Significantly reduced ratios of main organ weight to body weight at postnatal ages of 30 60 and 90 days were also observed

  9. Effects of Low-Dose Drinking Water Arsenic on Mouse Fetal and Postnatal Growth and Development

    PubMed Central

    Kozul-Horvath, Courtney D.; Zandbergen, Fokko; Jackson, Brian P.; Enelow, Richard I.; Hamilton, Joshua W.

    2012-01-01

    Background Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). Methodology and Findings C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Conclusions/Significance Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations. PMID:22693606

  10. The Development of Upper Limb Movements: From Fetal to Post-Natal Life

    PubMed Central

    Zoia, Stefania; Blason, Laura; D’Ottavio, Giuseppina; Biancotto, Marina; Bulgheroni, Maria; Castiello, Umberto

    2013-01-01

    Background The aim of this longitudinal study was to investigate how the kinematic organization of upper limb movements changes from fetal to post-natal life. By means of off-line kinematical techniques we compared the kinematics of hand-to-mouth and hand-to-eye movements, in the same individuals, during prenatal life and early postnatal life, as well as the kinematics of hand-to-mouth and reaching-toward-object movements in the later age periods. Methodology/Principal Findings Movements recorded at the 14th, 18th and 22nd week of gestation were compared with similar movements recorded in an ecological context at 1, 2, 3, 4, 8, and 12 months after birth. The results indicate a similar kinematic organization depending on movement type (i.e., eye, mouth) for the infants at one month and for the fetuses at 22 weeks of gestation. At two and three months such differential motor planning depending on target is lost and no statistical differences emerge. Hand to eye movements were no longer observed after the fourth month of life, therefore we compared kinematics for hand to mouth with hand to object movements. Results of these analyses revealed differences in the performance of hand to mouth and reaching to object movements in the length of the deceleration phase of the movement, depending on target. Conclusion/Significance Data are discussed in terms of how the passage from intrauterine to extra-uterine environments modifies motor planning. These results provide novel evidence of how different types of upper extremity movements, those directed towards one’s own face and those directed to external objects, develop. PMID:24324642

  11. Effects of low-dose drinking water arsenic on mouse fetal and postnatal growth and development.

    PubMed

    Kozul-Horvath, Courtney D; Zandbergen, Fokko; Jackson, Brian P; Enelow, Richard I; Hamilton, Joshua W

    2012-01-01

    Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations.

  12. Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

    PubMed

    Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

    2015-04-01

    Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

  13. Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy

    PubMed Central

    Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

    2016-01-01

    Abstract To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy. In the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment. PMID:26945416

  14. Maternal Pre- and Postnatal Mental Health Trajectories and Child Mental Health and Development: Prospective Study in a Normative and Formerly Infertile Sample

    ERIC Educational Resources Information Center

    Vanska, Mervi; Punamaki, Raija-Leena; Tolvanen, Asko; Lindblom, Jallu; Flykt, Marjo; Unkila-Kallio, Leila; Tiitinen, Aila; Repokari, Leena; Sinkkonen, Jari; Tulppala, Maija

    2011-01-01

    Pregnancy and early motherhood involve uncertainty and change, which can evoke mental health problems. We identified maternal mental health trajectories in pre- and postnatal period, and examined their association with later child mental health and development. Finnish mothers reported psychological distress (General Health Questionnaire [GHQ-36])…

  15. Maternal Pre- and Postnatal Mental Health Trajectories and Child Mental Health and Development: Prospective Study in a Normative and Formerly Infertile Sample

    ERIC Educational Resources Information Center

    Vanska, Mervi; Punamaki, Raija-Leena; Tolvanen, Asko; Lindblom, Jallu; Flykt, Marjo; Unkila-Kallio, Leila; Tiitinen, Aila; Repokari, Leena; Sinkkonen, Jari; Tulppala, Maija

    2011-01-01

    Pregnancy and early motherhood involve uncertainty and change, which can evoke mental health problems. We identified maternal mental health trajectories in pre- and postnatal period, and examined their association with later child mental health and development. Finnish mothers reported psychological distress (General Health Questionnaire [GHQ-36])…

  16. KSGal6ST Is Essential for the 6-Sulfation of Galactose within Keratan Sulfate in Early Postnatal Brain

    PubMed Central

    Hoshino, Hitomi; Foyez, Tahmina; Ohtake-Niimi, Shiori; Takeda-Uchimura, Yoshiko; Michikawa, Makoto; Kadomatsu, Kenji

    2014-01-01

    Keratan sulfate (KS) comprises repeating disaccharides of galactose (Gal) and N-acetylglucosamine (GlcNAc). Residues of Gal and GlcNAc in KS are potentially modified with sulfate at their C-6 positions. The 5D4 monoclonal antibody recognizes KS structures containing Gal and GlcNAc, both 6-sulfated, and has been used most extensively to evaluate KS expression in mammalian brains. We previously showed that GlcNAc6ST1 is an enzyme responsible for the synthesis of the 5D4 epitope in developing brain and in the adult brain, where it is induced after injury. It has been unclear which sulfotransferase is responsible for Gal-6-sulfation within the 5D4 KS epitope in developing brains. We produced mice deficient in KSGal6ST, a Gal-6-sulfotransferase. Western blotting and immunoprecipitation revealed that all 5D4-immunoreactivity to proteins, including phosphacan, were abolished in KSGal6ST-deficient postnatal brains. Likewise, the 5D4 epitope, expressed primarily in the cortical marginal zone and subplate and dorsal thalamus, was eliminated in KSGal6ST-deficient mice. Disaccharide analysis showed the loss of Gal-6-sulfate in KS of the KSGal6ST-deficient brains. Transfection studies revealed that GlcNAc6ST1 and KSGal6ST cooperated in the expression of the 5D4 KS epitope in HeLa cells. These results indicate that KSGal6ST is essential for C-6 sulfation of Gal within KS in early postnatal brains. PMID:24152993

  17. Prenatal epoxiconazole exposure effects on rat postnatal development.

    PubMed

    de Castro, Vera L S S; Maia, Aline H

    2012-04-01

    Although some studies have pointed out to embryo/fetal toxicity, knowledge about the potential toxicity of the fungicide epoxiconazole is still limited. Once the results of these previous studies have raised some concern, this study studied the effects of epoxiconazole maternal exposure on the physical endpoints in the development of rat pups. To accomplish that, the effects of epoxiconazole (50.0, 100.0, and 150.0  mg/kg) were examined when rats were exposed at two different developmental stages: during the first 6 days of pregnancy or in the organogenesis period (6-15 days). After parturition, pups were tested for growth and maturational milestones. Maternal exposure to the fungicide, independently of phase, resulted in significantly early mean time to vaginal opening and delayed time to testes descent in pups. Weight gain rate in pups and their mothers was not affected for the tested exposure period. The findings of this study emphasize that epoxiconazole maternal exposure may lead to alterations in developmental patterns in nursing pups, consistent with the known influence of epoxiconazole on steroid hormone synthesis.

  18. Embryonic and postnatal development of masticatory and tongue muscles.

    PubMed

    Yamane, A

    2005-11-01

    This review summarizes findings concerning the unique developmental characteristics of mouse head muscles (mainly the masticatory and tongue muscles) and compares their characteristics with those of other muscles. The developmental origin of the masticatory muscles is the somitomeres, whereas the tongue and other muscles, such as the trunk (deep muscles of the back, body wall muscles) and limb muscles, originate from the somites. The program controlling the early stages of masticatory myogenesis, such as the specification and migration of muscle progenitor cells, is distinctly different from those in trunk and limb myogenesis. Tongue myogenesis follows a similar regulatory program to that for limb myogenesis. Myogenesis and synaptogenesis in the masticatory muscles are delayed in comparison with other muscles and are not complete even at birth, whereas the development of tongue muscles proceeds faster than those of other muscles and ends at around birth. The regulatory programs for masticatory and tongue myogenesis seem to depend on the developmental origins of the muscles, i.e., the origin being either a somite or somitomere, whereas myogenesis and synaptogenesis seem to progress to serve the functional requirements of the masticatory and tongue muscles.

  19. Embryonic and postnatal development of the layer I-directed ("matrix") thalamocortical system in the rat.

    PubMed

    Galazo, Maria J; Martinez-Cerdeño, Verónica; Porrero, César; Clascá, Francisco

    2008-02-01

    Inputs to the layer I apical dendritic tufts of pyramidal cells are crucial in "top-down" interactions in the cerebral cortex. A large population of thalamocortical cells, the "matrix" (M-type) cells, provides a direct robust input to layer I that is anatomically and functionally different from the thalamocortical input to layer VI. The developmental timecourse of M-type axons is examined here in rats aged E (embryonic day) 16 to P (postnatal day) 30. Anterograde techniques were used to label axons arising from 2 thalamic nuclei mainly made up of M-type cells, the Posterior and the Ventromedial. The primary growth cones of M-type axons rapidly reached the subplate of dorsally situated cortical areas. After this, interstitial branches would sprout from these axons under more lateral cortical regions to invade the overlying cortical plate forming secondary arbors. Moreover, retrograde labeling of M-type cell somata in the thalamus after tracer deposits confined to layer I revealed that large numbers of axons from multiple thalamic nuclei had already converged in a given spot of layer I by P3. Because of early ingrowth in such large numbers, interactions of M-type axons may significantly influence the early development of cortical circuits.

  20. Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions

    PubMed Central

    Brinegar, Amy E; Xia, Zheng; Loehr, James Anthony; Li, Wei; Rodney, George Gerald

    2017-01-01

    Postnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here, we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first 2 weeks after birth are particularly dynamic for differential gene expression and alternative splicing transitions, and calcium-handling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of the three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin target Nfatc3, and/or affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development. PMID:28826478

  1. Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions.

    PubMed

    Brinegar, Amy E; Xia, Zheng; Loehr, James Anthony; Li, Wei; Rodney, George Gerald; Cooper, Thomas A

    2017-08-11

    Postnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here, we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first 2 weeks after birth are particularly dynamic for differential gene expression and alternative splicing transitions, and calcium-handling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of the three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin target Nfatc3, and/or affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development.

  2. CD90 and CD105 expression in the mouse ovary and testis at different stages of postnatal development.

    PubMed

    Tepekoy, Filiz; Ozturk, Saffet; Sozen, Berna; Ozay, Recep S; Akkoyunlu, Gokhan; Demir, Necdet

    2015-12-01

    CD90 (i.e., THY1) and CD105 (i.e., endoglin) are glycoproteins known as mesenchymal stem cell markers that are expressed in various cell types including male and female gonadal cells. We aimed to determine ovarian and testicular expression of CD90 and CD105 in various cell types during postnatal development in mice. The present study was carried out on male (C57BL/6) and female (Balb/C) mice during critical stages of gonadal development. Immunohistochemical localization of CD90 and CD105 was determined in the ovaries obtained at postnatal days (PND) -1, -7, -21 and -60 and in the testes obtained at PND6, -8, -16, -20, -29, -32 and -88. The relative expression of CD90 and CD105 was evaluated by ImageJ software and data were analyzed by analysis of variance. The relative expression of CD90 and CD105 varied during postnatal development and increased significantly in the adult ovary (PND60) and testis (PND88) compared to the early postnatal gonads. In the ovaries, the expression of CD90 was significantly higher in somatic cells in comparison to germ cell compartments. In the testis, CD90 expression was greater in germ cells and Sertoli cells compared to other cell types. Expression of CD105 was higher in germ cells than somatic cells of both the ovary and testis. In addition to different expression of CD90 and CD105 during various developmental stages, also their altered expression in particular cell types suggests specific roles of these glycoproteins in physiological processes of mouse gonads.

  3. Postnatal Leptin Promotes Organ Maturation and Development in IUGR Piglets

    PubMed Central

    Attig, Linda; Brisard, Daphné; Larcher, Thibaut; Mickiewicz, Michal; Guilloteau, Paul; Boukthir, Samir; Niamba, Claude-Narcisse; Gertler, Arieh; Djiane, Jean; Monniaux, Danielle; Abdennebi-Najar, Latifa

    2013-01-01

    Babies with intra-uterine growth restriction (IUGR) are at increased risk for experiencing negative neonatal outcomes due to their general developmental delay. The present study aimed to investigate the effects of a short postnatal leptin supply on the growth, structure, and functionality of several organs at weaning. IUGR piglets were injected from day 0 to day 5 with either 0.5 mg/kg/d leptin (IUGRLep) or saline (IUGRSal) and euthanized at day 21. Their organs were collected, weighed, and sampled for histological, biochemical, and immunohistochemical analyses. Leptin induced an increase in body weight and the relative weights of the liver, spleen, pancreas, kidneys, and small intestine without any changes in triglycerides, glucose and cholesterol levels. Notable structural and functional changes occurred in the ovaries, pancreas, and secondary lymphoid organs. The ovaries of IUGRLep piglets contained less oogonia but more oocytes enclosed in primordial and growing follicles than the ovaries of IUGRSal piglets, and FOXO3A staining grade was higher in the germ cells of IUGRLep piglets. Within the exocrine parenchyma of the pancreas, IUGRLep piglets presented a high rate of apoptotic cells associated with a higher trypsin activity. In the spleen and the Peyer’s patches, B lymphocyte follicles were much larger in IUGRLep piglets than in IUGRSal piglets. Moreover, IUGRLep piglets showed numerous CD79+cells in well-differentiated follicle structures, suggesting a more mature immune system. This study highlights a new role for leptin in general developmental processes and may provide new insight into IUGR pathology. PMID:23741353

  4. Role of sensory-motor cortex activity in postnatal development of corticospinal axon terminals in the cat.

    PubMed

    Friel, Kathleen M; Martin, John H

    2005-04-25

    The initial pattern of corticospinal (CS) terminations, as axons grow into the spinal gray matter, bears little resemblance to the pattern later in development and in maturity. This is because of extensive axon pruning and local axon terminal growth during early postnatal development. Pruning is driven by activity-dependent competition between the CS systems on each side during postnatal weeks (PW) 3-7. It is not known whether CS axon terminal growth and final topography are activity dependent. We examined the activity dependence of CS axon terminal growth and topography at different postnatal times. We inactivated sensory-motor cortex by infusion of the gamma-aminobutyric acid type A (GABA(A)) agonist muscimol and traced CS axons from the inactivated side. Inactivation between PW5 and PW7 produced permanent changes in projection topography, reduced local axon branching, and prevented development of dense clusters of presynaptic sites, which are normally characteristic of CS terminals. Inactivation at younger (PW3-5) and older (PW8-12) ages did not affect projection topography but impeded development of local axon branching and presynaptic site clusters. These effects were not due to increased cortical cell death during inactivation. Neural activity plays an important role in determining the morphology of CS terminals during the entire period of development, but, for the projection topography, the role of activity is exercised during a very brief period. This points to a complex, and possibly independent, regulation of termination topography and terminal morphology. Surprisingly, when a CS neuron's activity is blocked during early development, it does not recover lost connections later in development once activity resumes.

  5. Early postnatal rat ventricle resection leads to long‐term preserved cardiac function despite tissue hypoperfusion

    PubMed Central

    Zogbi, Camila; Saturi de Carvalho, Ana E. T.; Nakamuta, Juliana S.; Caceres, Viviane de M.; Prando, Silvana; Giorgi, Maria C. P.; Rochitte, Carlos E.; Meneghetti, Jose C.; Krieger, Jose E.

    2014-01-01

    Abstract One‐day‐old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long‐term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End‐Diastolic Pressure–Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long‐term preservation of cardiac function despite tissue hypoperfusion. PMID:25168870

  6. Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study

    PubMed Central

    Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

    2015-01-01

    Objective To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Study design Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Results Mean length-for-age z score was −0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m2; 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (−41.5 g per twofold increase in ferritin; 95% CI −78 to −5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of −0.06 per 20 nmol/L; 95% CI −0.11 to −0.01) was observed. Conclusions Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. PMID:25246090

  7. Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats.

    PubMed

    Brake, Wayne G; Zhang, Tie Yuan; Diorio, Josie; Meaney, Michael J; Gratton, Alain

    2004-04-01

    While many experiment with drugs, relatively few individuals develop a true addiction. We hypothesized that, in rats, such individual differences in the actions of addictive drugs might be determined by postnatal rearing conditions. To test this idea, we investigated whether stimulant- and stress-induced activation of nucleus accumbens dopamine transmission and dopamine-dependent behaviours might differ among adults rats that had been either repeatedly subjected to prolonged maternal separation or a brief handling procedure or left undisturbed (non-handled) during the first 14 days of life. We found that, in comparison with their handled counterparts, maternally separated and non-handled animals are hyperactive when placed in a novel setting, display a dose-dependent higher sensitivity to cocaine-induced locomotor activity and respond to a mild stressor (tail-pinch) with significantly greater increases in nucleus accumbens dopamine levels. In addition, maternally separated animals were found to sensitize to the locomotor stimulant action of amphetamine when repeatedly stressed under conditions that failed to sensitize handled and non-handled animals. Finally, quantitative receptor autoradiography revealed a lower density of nucleus accumbens-core and striatal dopamine transporter sites in maternally separated animals. Interestingly, we also found greatly reduced D(3) dopamine receptor binding and mRNA levels in the nucleus accumbens-shell of handled animals. Together, these findings provide compelling evidence that disruptions in early postnatal rearing conditions can lead to profound and lasting changes in the responsiveness of mesocorticolimbic dopamine neurons to stress and psychostimulants, and suggest a neurobiological basis for individual differences in vulnerability to compulsive drug taking.

  8. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    PubMed Central

    Lim, Wei Ling; Idris, Marshita Mohd; Kevin, Felix Suresh; Soga, Tomoko; Parhar, Ishwar S.

    2016-01-01

    Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13–20. Confocal imaging was used to examine the spine density of EGFP–GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP–GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood. PMID:27630615

  9. The effects of stress during early postnatal periods on behavior and hippocampal neuroplasticity markers in adult male mice.

    PubMed

    van der Kooij, M A; Grosse, J; Zanoletti, O; Papilloud, A; Sandi, C

    2015-12-17

    Infancy is a critical period for brain development. Emerging evidence indicates that stress experienced during that period can have long-term programming effects on the brain and behavior. However, whether different time periods represent different vulnerabilities to the programming of different neurobehavioral domains is not yet known. Disrupted maternal care is known to interfere with neurodevelopmental processes and may lead to the manifestation of behavioral abnormalities in adulthood. Mouse dams confronted with insufficient bedding/nesting material have been shown to provide fragmented maternal care to their offspring. Here, we compared the impact of this model of early-life stress (ELS) during different developmental periods comprising either postnatal days (PNDs) 2-9 (ELS-early) or PND 10-17 (ELS-late) on behavior and hippocampal cell adhesion molecules in male mice in adulthood. ELS-early treatment caused a permanent reduction in bodyweight, whereas this reduction only occurred transiently during juvenility in ELS-late mice. Anxiety was only affected in ELS-late mice, while cognition and sociability were equally impaired in both ELS-treated groups. We analyzed hippocampal gene expression of the γ2 subunit of the GABAa receptor (Gabrg2) and of genes encoding cell adhesion molecules. Gabrg2 expression was increased in the ventral hippocampus in ELS-late-treated animals and was correlated with anxiety-like behavior in the open-field (OF) test. ELS-early-treated animals exhibited an increase in nectin-1 expression in the dorsal hippocampus, and this increase was associated with the social deficits seen in these animals. Our findings highlight the relevance of developmental age on stress-induced long-term behavioral alterations. They also suggest potential links between early stress-induced alterations in hippocampal Gabrg2 expression and the developmental programming of anxiety and between changes in hippocampal nectin-1 expression and stress-induced social

  10. Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary.

    PubMed

    Asadi-Azarbaijani, Babak; Santos, Regiane R; Jahnukainen, Kirsi; Braber, Saskia; van Duursen, Majorie B M; Toppari, Jorma; Saugstad, Ola D; Nurmio, Mirja; Oskam, Irma C

    2017-03-01

    Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (P<0.01), oogonia (p<0.01) and germline clusters (P<0.05), decreased activation of primordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats

    PubMed Central

    Navarro, Daniela; Alvarado, Mayvi; Navarrete, Francisco; Giner, Manuel; Obregon, Maria Jesus; Manzanares, Jorge; Berbel, Pere

    2015-01-01

    Thyroid hormones are fundamental for the expression of genes involved in the development of the CNS and their deficiency is associated with a wide spectrum of neurological diseases including mental retardation, attention deficit-hyperactivity disorder and autism spectrum disorders. We examined in rat whether developmental and early postnatal hypothyroidism affects the distribution of vesicular glutamate transporter-1 (VGluT1; glutamatergic) and vesicular inhibitory amino acid transporter (VGAT; GABAergic) immunoreactive (ir) boutons in the hippocampus and somatosensory cortex, and the behavior of the pups. Hypothyroidism was induced by adding 0.02% methimazole (MMI) and 1% KClO4 to the drinking water starting at embryonic day 10 (E10; developmental hypothyroidism) and E21 (early postnatal hypothyroidism) until day of sacrifice at postnatal day 50. Behavior was studied using the acoustic prepulse inhibition (somatosensory attention) and the elevated plus-maze (anxiety-like assessment) tests. The distribution, density and size of VGluT1-ir and VGAT-ir boutons in the hippocampus and somatosensory cortex was abnormal in MMI pups and these changes correlate with behavioral changes, as prepulse inhibition of the startle response amplitude was reduced, and the percentage of time spent in open arms increased. In conclusion, both developmental and early postnatal hypothyroidism significantly decreases the ratio of GABAergic to glutamatergic boutons in dentate gyrus leading to an abnormal flow of information to the hippocampus and infragranular layers of the somatosensory cortex, and alter behavior in rats. Our data show cytoarchitectonic alterations in the basic excitatory hippocampal loop, and in local inhibitory circuits of the somatosensory cortex and hippocampus that might contribute to the delayed neurocognitive outcome observed in thyroid hormone deficient children born in iodine deficient areas, or suffering from congenital hypothyroidism. PMID:25741243

  12. Postnatal Light Effects on Pup Stress Axis Development Are Independent of Maternal Behavior

    PubMed Central

    Coleman, Georgia; Canal, Maria M.

    2017-01-01

    Postnatal environment shapes brain development during key critical periods. We have recently found that postnatal light environment has long-term effects on the stress and circadian systems, which can lead to altered stress responses, circadian behavior and a depressive phenotype in adulthood. However, it is still unclear how light experience affects the postnatal development of specific stress markers in the pup brain and the role played by maternal behavior and stress. To test this, we raised mice under either light-dark cycles (LD), constant light (LL) or constant darkness (DD) during the suckling stage. After weaning, all mice were exposed to LD until adulthood. Results show that postnatal light environment does not have any significant effects on dam stress levels (plasma corticosterone concentration, Arginine-vasopressin and Glucocorticoid receptor (GR) protein expression in the brain) or maternal behavior, including licking and grooming. Light environment does not have a major effect on litter characteristics or pup growth either. Interestingly, light environment during the suckling stage significantly impacted Corticotrophin-releasing hormone (CRH) and Gr mRNA expression in pup brain during development. Furthermore, a difference in Crh mRNA expression between LL- and DD-raised mice was still observed in adulthood, long after the exposure to abnormal light environments had stopped. Taken together, these data suggest that the long-term effects of postnatal light environment on the pups' stress system cannot be attributed to alterations in either maternal behavior and/or stress axis function. Instead, postnatal light experience may act directly on the pup stress axis and/or indirectly via circadian system alterations. PMID:28239333

  13. Postnatal Light Effects on Pup Stress Axis Development Are Independent of Maternal Behavior.

    PubMed

    Coleman, Georgia; Canal, Maria M

    2017-01-01

    Postnatal environment shapes brain development during key critical periods. We have recently found that postnatal light environment has long-term effects on the stress and circadian systems, which can lead to altered stress responses, circadian behavior and a depressive phenotype in adulthood. However, it is still unclear how light experience affects the postnatal development of specific stress markers in the pup brain and the role played by maternal behavior and stress. To test this, we raised mice under either light-dark cycles (LD), constant light (LL) or constant darkness (DD) during the suckling stage. After weaning, all mice were exposed to LD until adulthood. Results show that postnatal light environment does not have any significant effects on dam stress levels (plasma corticosterone concentration, Arginine-vasopressin and Glucocorticoid receptor (GR) protein expression in the brain) or maternal behavior, including licking and grooming. Light environment does not have a major effect on litter characteristics or pup growth either. Interestingly, light environment during the suckling stage significantly impacted Corticotrophin-releasing hormone (CRH) and Gr mRNA expression in pup brain during development. Furthermore, a difference in Crh mRNA expression between LL- and DD-raised mice was still observed in adulthood, long after the exposure to abnormal light environments had stopped. Taken together, these data suggest that the long-term effects of postnatal light environment on the pups' stress system cannot be attributed to alterations in either maternal behavior and/or stress axis function. Instead, postnatal light experience may act directly on the pup stress axis and/or indirectly via circadian system alterations.

  14. Development of immunity in early life.

    PubMed

    Goenka, Anu; Kollmann, Tobias R

    2015-06-01

    The immune system in early life goes through rapid and radical changes. Early life is also the period with the highest risk of infections. The foetal immune system is programmed to coexist with foreign antigenic influences in utero, and postnatally to rapidly develop a functional system capable of distinguishing helpful microbes from harmful pathogens. Both host genetics and environmental influences shape this dramatic transition and direct the trajectory of the developing immune system into early childhood and beyond. Given the malleability of the immune system in early life, interventions aimed at modulating this trajectory thus have the potential to translate into considerable reductions in infectious disease burden with immediate as well as long-lasting benefit. However, an improved understanding of the underlying molecular drivers of early life immunity is prerequisite to optimise such interventions and transform the window of early life vulnerability into one of opportunity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  15. Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology.

    PubMed

    Louveau, I; Perruchot, M-H; Bonnet, M; Gondret, F

    2016-11-01

    Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants. In contrast to other tissues, the embryonic origin of adipose cells remains the subject of debate. Adipose cells arise from the recruitment of specific multipotent stem cells/progenitors named adipose tissue-derived stromal cells. Recent studies have highlighted the existence of a variety of those cells being able to differentiate into white, brown or brown-like/beige adipocytes. After commitment to the adipocyte lineage, progenitors undergo large changes in the expression of many genes involved in cell cycle arrest, lipid accumulation and secretory functions. Early nutrition can affect these processes during fetal and perinatal periods and can also influence or pre-determinate later growth of adipose tissue. How these changes may be related to adipose tissue functional maturity around birth and can influence newborn survival is discussed. Altogether, a better knowledge of fetal and postnatal adipose tissue development is important for various aspects of animal production, including neonatal survival, postnatal growth efficiency and health.

  16. Cerebellar hypoplasia in three sibling cats after intrauterine or early postnatal parvovirus infection.

    PubMed

    Aeffner, F; Ulrich, R; Schulze-Rückamp, L; Beineke, A

    2006-11-01

    The present report describes the case of an intrauterine or early postnatal parvovirus infection with subsequent cerebellar hypoplasia in three kittens from the same litter. Clinical examination of affected cats revealed neurologic signs indicative of cerebellar ataxia. Due to poor prognosis, animals were euthanised and submitted for necropsy. Post mortem examination demonstrated variable degrees of cerebellar hypoplasia. Histologically, brain lesions were characterised by segmental loss of the external and internal granular layer and decreased numbers of Purkinje cells. Reactive proliferation of astrocytes in the central nervous system was verified by the detection of GFAP-expressing glial cells in affected areas using immunohistochemistry. Furthermore, parvovirus antigen was detected immunohistochemically in neuronal cells of the cerebellum, but not in other parts of the brain and spinal cord or non-neuronal tissues. The present report demonstrates the usefulness of post mortem examination and detection of viral antigen by immunohistochemistry for the discrimination of neurologic disorders in feline species. Neurologic deficiencies due to cerebellar hypoplasia caused by in utero or perinatal feline parvovirus infection should be taken into consideration as differential diagnoses for ataxia in neonatal and juvenile cats.

  17. Multi-stability of circadian phase wave within early postnatal suprachiasmatic nucleus.

    PubMed

    Jeong, Byeongha; Hong, Jin Hee; Kim, Hyun; Choe, Han Kyoung; Kim, Kyungjin; Lee, Kyoung J

    2016-02-19

    The suprachiasmatic nucleus (SCN) is a group of cells that functions as a biological master clock. In different SCN cells, oscillations of biochemical markers such as the expression-level of clock genes, are not synchronized but instead form slow circadian phase waves propagating over the whole cell population spatio-temporal structure is a fixed property set by the anatomy of a given SCN. Here, we show that this is not the case in early postnatal SCN. Earlier studies presumed that their Based on bioluminescence imaging experiments with Per2-Luciferase mice SCN cultures which guided computer simulations of a realistic model of the SCN, we demonstrate that the wave is not unique but can be in various modes including phase- coherent oscillation, crescent-shaped wave, and most notably, a rotating pinwheel wave that conceptually resembles a wall clock with a rotating hand. Furthermore, mode transitions can be induced by a pulse of 38.5 °C temperature perturbation. Importantly, the waves support a significantly different period, suggesting that neither a spatially-fixed phase ordering nor a specialized pacemaker having a fixed period exist in these studied SCNs. These results lead to new important questions of what the observed multi-stability means for the proper function of an SCN and its arrhythmia.

  18. Multi-stability of circadian phase wave within early postnatal suprachiasmatic nucleus

    PubMed Central

    Jeong, Byeongha; Hong, Jin Hee; Kim, Hyun; Choe, Han Kyoung; Kim, Kyungjin; Lee, Kyoung J.

    2016-01-01

    The suprachiasmatic nucleus (SCN) is a group of cells that functions as a biological master clock. In different SCN cells, oscillations of biochemical markers such as the expression-level of clock genes, are not synchronized but instead form slow circadian phase waves propagating over the whole cell population spatio-temporal struc- ture is a fixed property set by the anatomy of a given SCN. Here, we show that this is not the case in early postnatal SCN. Earlier studies presumed that their Based on bioluminescence imaging experiments with Per2-Luciferase mice SCN cultures which guided computer simulations of a realistic model of the SCN, we demonstrate that the wave is not unique but can be in various modes including phase- coherent oscillation, crescent-shaped wave, and most notably, a rotating pinwheel wave that conceptually resembles a wall clock with a rotating hand. Furthermore, mode transitions can be induced by a pulse of 38.5 °C temperature perturbation. Importantly, the waves support a significantly different period, suggesting that neither a spatially-fixed phase ordering nor a specialized pacemaker having a fixed period exist in these studied SCNs. These results lead to new important questions of what the observed multi-stability means for the proper function of an SCN and its arrhythmia. PMID:26891917

  19. The effect of gestational ethanol exposure on voluntary ethanol intake in early postnatal and adult rats.

    PubMed

    Youngentob, Steven L; Molina, Juan C; Spear, Norman E; Youngentob, Lisa M

    2007-12-01

    Clinical and epidemiological studies provide strong data for a relationship between prenatal ethanol exposure and the risk for abuse in adolescent and young adult humans. However, drug-acceptance results in response to fetal exposure have differed by study, age at evaluation, and experimental animal. In the present study, the authors tested whether voluntary ethanol intake was enhanced in both the infantile and adult rat (15 and 90 days of age, respectively), as a consequence of chronic fetal drug experience. Experimental rats were exposed in utero by administering ethanol to a pregnant dam in a liquid diet during gestational Days 6-20. Compared with those for isocaloric pair-fed and ad lib chow control animals, the results for experimental animals demonstrated that fetal exposure significantly increased infantile affinity for ethanol ingestion without affecting intake patterns of an alternative fluid (water). Heightened affinity for ethanol was absent in adulthood. Moreover, the results argue against malnutrition as a principal factor underlying the infantile phenomenon. These data add to a growing literature indicative of heightened early postnatal acceptance patterns resulting from maternal use or abuse of ethanol during pregnancy.

  20. Effects of early postnatal gonadal steroids on extinction of a continuously food-rewarded running response.

    PubMed

    Enriquez, P; Calés, J M; Sánchez-Santed, F; Guillamón, A

    1991-01-01

    In the present work the existence of sex differences (Experiment 1) on the acquisition and extinction of a continuously reinforced response in a short and narrow runway (100 x 9 x 10 cm) were investigated. In addition to the investigation of the basic sex differences in Experiment 1, the effect of postpuberal gonadectomy of male and female rats and the role of the early postnatal gonadal steroids on these situations were also examined in Experiments 2 and 3, respectively. In all experiments, no sex differences were found in acquisition. However, males extinguished faster than female rats. Gonadectomy of both sexes in adulthood, although it increases their latencies in acquisition, did not affect the differences between sexes during extinction. In contrast, in Experiment 3 female androgenization and male orchidectomy on day one after birth reversed the direction of sex differences found between control rats in the extinction period. Our findings suggests that the observed sex differences in extinction may be due to an underlying sexual dimorphism in the response inhibition process.

  1. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies

    PubMed Central

    Yu, Grace Z.; Aye, Christina Y.L.; Lewandowski, Adam J.; Davis, Esther F.; Khoo, Cheen P.; Newton, Laura; Yang, Cheng T.; Al Haj Zen, Ayman; Simpson, Lisa J.; O’Brien, Kathryn; Cook, David A.; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M.; Watt, Suzanne M.

    2016-01-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (−17.7±16.4% versus −9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth. PMID:27456522

  2. Histological study on hippocampus, amygdala and cerebellum following low lead exposure during prenatal and postnatal brain development in rats.

    PubMed

    Barkur, Rajashekar Rao; Bairy, Laxminarayana K

    2016-06-01

    Neuropsychological studies in children who are exposed to lead during their early brain development have shown to develop behavioural and cognitive deficit. The aim of the present study was to assess the cellular damage in hippocampus, amygdala and cerebellum of rat pups exposed to lead during different periods of early brain development. Five groups of rat pups were investigated. (a) Control group (n = 8) (mothers of these rats were given normal drinking water throughout gestation and lactation), (b) pregestation lead-exposed group (n = 8) (mothers of these rats were exposed to 0.2% lead acetate in the drinking water for one month before conception), (c) gestation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout gestation [gestation day 01 to day 21]), (d) lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout lactation [postnatal day 01 to day 21]) and (e) gestation and lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate throughout gestation and lactation). On postnatal day 30, rat pups of all the groups were killed. Numbers of surviving neurons in the hippocampus, amygdala and cerebellum regions were counted using cresyl violet staining technique. Histological data indicate that lead exposure caused significant damage to neurons of hippocampus, amygdala and cerebellum regions in all lead-exposed groups except lactation lead-exposed group. The extent of damage to neurons of hippocampus, amygdala and cerebellum regions in lactation lead-exposed group was comparable to gestation and lactation groups even though the duration of lead exposure was much less in lactation lead-exposed group. To conclude, the postnatal period of brain development seems to be more vulnerable to lead neurotoxicity compared to prenatal period of brain development. © The Author(s) 2014.

  3. Attractive action of FGF-signaling contributes to the postnatal developing hippocampus.

    PubMed

    Cuccioli, V; Bueno, C; Belvindrah, R; Lledo, P-M; Martinez, S

    2015-04-01

    During brain development neural cell migration is a crucial, well-orchestrated, process, which leads to the proper whole brain structural organization. As development proceeds, new neurons are continuously produced, and this protracted neurogenesis is maintained throughout life in specialized germinative areas inside the telencephalon: the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. In the anterior SVZ, newly generated neurons migrate through long distances, along the rostral migratory stream (RMS), before reaching their final destinations in the olfactory bulb (OB). Intriguingly, recent observations pointed out the existence of other postnatal tangential routes of migration alternative to the RMS but still starting from the SVZ. The presence of such dynamic and heterogeneous cell movements contributes to important features in the postnatal brain such as neural cell replacement and plasticity in cortical regions. In this work, we asked whether a caudal migratory pathway starting from the caudal SVZ continues through life. Strikingly, in vivo analysis of this caudal migration revealed the presence of a postnatal contribution of SVZ to the hippocampus. In vitro studies of the caudal migratory stream revealed the role of FGF signaling in attracting caudally the migrating neuroblasts during postnatal stages. Our findings demonstrate a postnatal neuronal contribution from the caudal ganglionic eminence (CGE) CGE-SVZ to the hippocampus through an FGF-dependent migrating mechanism. All together our data emphasizes the emerging idea that a developmental program is still operating in discrete domains of the postnatal brain and may contribute to the regulation of neural cell replacement processes in physiological plasticity and/or pathological circumstances.

  4. Ozone-induced airway epithelial cell death, the neurokinin-1 receptor pathway, and the postnatal developing lung

    PubMed Central

    Murphy, Shannon R.; Oslund, Karen L.; Hyde, Dallas M.; Miller, Lisa A.; Van Winkle, Laura S.

    2014-01-01

    Children are uniquely susceptible to ozone because airway and lung growth continue for an extensive period after birth. Early-life exposure of the rhesus monkey to repeated ozone cycles results in region-specific disrupted airway/lung growth, but the mediators and mechanisms are poorly understood. Substance P (SP), neurokinin-1 receptor (NK-1R); and nuclear receptor Nur77 (NR4A1) are signaling pathway components involved in ozone-induced cell death. We hypothesize that acute ozone (AO) exposure during postnatal airway development disrupts SP/NK-1R/Nur77 pathway expression and that these changes correlate with increased ozone-induced cell death. Our objectives were to 1) spatially define the normal development of the SP/NK-1R/Nur77 pathway in conducting airways; 2) compare how postnatal age modulates responses to AO exposure; and 3) determine how concomitant, episodic ozone exposure modifies age-specific acute responses. Male infant rhesus monkeys were assigned at age 1 mo to two age groups, 2 or 6 mo, and then to one of three exposure subgroups: filtered air (FA), FA+AO (AO: 8 h/day × 2 days), or episodic biweekly ozone exposure cycles (EAO: 8 h/day × 5 days/14-day cycle+AO). O3 = 0.5 ppm. We found that 1) ozone increases SP/NK-1R/Nur77 pathway expression in conducting airways, 2) an ozone exposure cycle (5 days/cycle) delivered early at age 2 mo resulted in an airway that was hypersensitive to AO exposure at the end of 2 mo, and 3) continued episodic exposure (11 cycles) resulted in an airway that was hyposensitive to AO exposure at 6 mo. These observations collectively associate with greater overall inflammation and epithelial cell death, particularly in early postnatal (2 mo), distal airways. PMID:25063800

  5. Postnatal development of neurons, interneurons and glial cells in the substantia nigra of mice.

    PubMed

    Abe, Manami; Kimoto, Hiroki; Eto, Risa; Sasaki, Taeko; Kato, Hiroyuki; Kasahara, Jiro; Araki, Tsutomu

    2010-08-01

    We investigated postnatal alterations of neurons, interneurons and glial cells in the mouse substantia nigra using immunohistochemistry. Tyrosine hydroxylase (TH), neuronal nuclei (NeuN), parvalbumin (PV), neuronal nitric oxide synthase (nNOS), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba 1), CNPase (2',3'-cyclic nucleotide 3'-phosphodiesterase), brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) immunoreactivity were measured in 1-, 2-, 4- and 8-week-old mice. In the present study, the maturation of NeuN-immunopositive neurons preceded the production of TH in the substantia nigra during postnatal development in mice. Furthermore, the maturation of nNOS-immunopositive interneurons preceded the maturation of PV-immunopositive interneurons in the substantia nigra during postnatal development. Among astrocytes, microglia and oligodendrocytes, in contrast, the development process of oligodendrocytes is delayed in the substantia nigra. Our double-labeled immunohistochemical study suggests that the neurotrophic factors such as BDNF and GDNF secreted by GFAP-positive astrocytes may play some role in maturation of neurons, interneurons and glial cells of the substantia nigra during postnatal development in mice. Thus, our findings provide valuable information on the development processes of the substantia nigra.

  6. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats

    PubMed Central

    Beaudin, Stephane A.; Strupp, Barbara J.; Strawderman, Myla; Smith, Donald R.

    2016-01-01

    Background: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. Objectives: To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Methods: Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1–21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Results: Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. Conclusions: This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230–237; http://dx.doi.org/10.1289/EHP258 PMID:27384154

  7. Postnatal Ovary Development in the Rat: Morphologic Study and Correlation of Morphology to Neuroendocrine Parameters

    PubMed Central

    Picut, Catherine A.; Dixon, Darlene; Simons, Michelle L.; Stump, Donald G.; Parker, George A.; Remick, Amera K.

    2014-01-01

    Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic–pituitary–gonadal axis matures. During the neonatal stage (postnatal day [PND] 0–7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of “atypical” follicles occurs in the early infantile period (PND 8–14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15–20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their “atypical” appearance. The juvenile stage (PND 21–32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33–37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat. PMID:25107574

  8. Postnatal ovary development in the rat: morphologic study and correlation of morphology to neuroendocrine parameters.

    PubMed

    Picut, Catherine A; Dixon, Darlene; Simons, Michelle L; Stump, Donald G; Parker, George A; Remick, Amera K

    2015-04-01

    Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic-pituitary-gonadal axis matures. During the neonatal stage (postnatal day [PND] 0-7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of "atypical" follicles occurs in the early infantile period (PND 8-14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15-20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their "atypical" appearance. The juvenile stage (PND 21-32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33-37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat.

  9. Synaptic and intrinsic balancing during postnatal development in rat pups exposed to valproic acid in utero.

    PubMed

    Walcott, Elisabeth C; Higgins, Emily A; Desai, Niraj S

    2011-09-14

    Valproic acid (VPA) is among the most teratogenic of commonly prescribed anticonvulsants, increasing the risk in humans of major malformations and impaired cognitive development. Likewise, rats exposed prenatally to VPA exhibit a variety of neuroanatomical and behavioral abnormalities. Previous work has shown that pyramidal neuron physiology in young VPA-exposed animals is marked by two strong abnormalities: an impairment in intrinsic neuronal excitability and an increase in NMDA synaptic currents. In this study, we investigated these abnormalities across postnatal development using whole-cell patch recordings from layer 2/3 neurons of medial prefrontal cortex. We found that both abnormalities were at a peak soon after birth but were gradually corrected as animals matured, to the extent that normal excitability and NMDA currents had been restored by early adolescence. The manner in which this correction happened suggested coordination between the two processes. Using computational models fitted to the physiological data, we argue that the two abnormalities trade off against each other, with the effects on network activity of the one balancing the effects of the other. This may constitute part of the nervous system's homeostatic response to teratogenic insult: an attempt to maintain stability despite a strong challenge.

  10. Postnatal care.

    PubMed

    Bullough, C H

    1988-04-01

    Early contact between mother and baby and early breastfeeding are essential elements of postnatal care. They promote bonding and a better breastfeeding performance, and cannot be overemphasized. Thereafter, in hospital practice, the next essential is a separation of abnormal from normal cases so that those in greatest need may receive the care they require. Commonly occurring postnatal problems should be managed according to standard protocols, so that effective management can be instituted by midwives or junior medical staff as necessary. Special attention must be paid to those with severe puerperal sepsis. There should be a readiness to recognize and treat such rare but curable conditions as acute tubular necrosis. Proper advice to the mother and the recording of significant events of the pregnancy in a document kept by the mother is the doctor's final responsibility.

  11. [Morphofunctional and biochemical properties of erythrocytes in early postnatal ontogenesis in rats in norm and after prenatal stress].

    PubMed

    Golubeva, E K; Nazarov, S B; Tomilova, I K

    2011-07-01

    Morphofunctional and biochemical properties of erythrocyte membrane were investigated in early postnatal ontogenesis in rats in norm and after prenatal immobilization stress. The transient decrease of erythrocyte membranes stability was revealed in the control rats. The ability to erythrocyte transformation and the concentration of lipid peroxidation products are increased. It has been shown by an increase of percentage discocytes and lower lipid peroxidation level that the erythrocyte membrane of the rats after prenatal stress is more stable.

  12. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: Association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP.

    PubMed

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A; Sumikawa, Katumi

    2015-02-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-D-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity.

  13. Effects of early postnatal exposure to ethanol on retinal ganglion cell morphology and numbers of neurons in the dorsolateral geniculate in mice

    PubMed Central

    Dursun, Ilknur; Jakubowska-Doğru, Ewa; van der List, Deborah; Liets, Lauren C.; Coombs, Julie L.; Berman, Robert F.

    2012-01-01

    examined in RGCs, soma area was significantly reduced and dendritic tortuosity significantly increased. After neonatal exposure to ethanol a decrease in total dendritic field area and an increase in the mean branch angle were also observed. Interestingly, RGC dendrite elongation and a decrease in the spine density were observed in the IC group, as compared to both ethanol-exposed and pure control subjects. There were no significant effects of alcohol exposure on total retinal area. Conclusion Early postnatal ethanol exposure affects development of the visual system, reducing the numbers of neurons in the GCL and in the dLGN, and altering RGCs’ morphology. PMID:21651582

  14. Postnatal depression and infant growth and development in low income countries: a cohort study from Goa, India

    PubMed Central

    Patel, V; DeSouza, N; Rodrigues, M

    2003-01-01

    Background: Postnatal depression is a recognised cause of delayed cognitive development in infants in developed countries. Being underweight is common in South Asia. Aims: To determine whether postnatal depression contributes to poor growth and development outcomes in Goa, India. Methods: Cohort study for growth outcomes with nested case-control study for developmental outcomes. A total of 171 babies were weighed and measured at 6–8 weeks following birth. The following measures were used: Edinburgh Postnatal Depression Scale for maternal mood, and sociodemographic and infant health variables. Outcome measures were: weight (<5th centile), length (<5th centile), and Developmental Assessment Scale for Indian Infants scores at six months. Results: Postnatal depression was a strong, and independent, predictor of low weight and length and was significantly associated with adverse mental development quotient scores. Conclusions: This study provides evidence for the first time that postnatal depression, a potentially treatable disorder, is a cause of poor growth and development in South Asia. PMID:12495957

  15. Postnatal development and plasticity of specialized muscle fiber characteristics in the hindlimb.

    PubMed

    Garry, D J; Bassel-Duby, R S; Richardson, J A; Grayson, J; Neufer, P D; Williams, R S

    1996-01-01

    Recent progress in defining molecular components of pathways controlling early stages of myogenesis has been substantial, but regulatory factors that govern the striking functional specialization of adult skeletal muscle fibers in vertebrate organisms have not yet been identified. A more detailed understanding of the temporal and spatial patterns by which specialized fiber characteristics arise may provide clues to the identity of the relevant regulatory factors. In this study, we used immunohistochemical, in situ hybridization, and Northern blot analyses to examine the time course and spatial characteristics of expression of myoglobin protein and mRNA during development of the distal hindlimb in the mouse. In adult animals, myoglobin is expressed selectively in oxidative, mitochondria-rich, fatigue-resistant myofibers, and it provides a convenient marker for this particular subset of specialized fibers. We observed only minimal expression of myoglobin in the hindlimb prior to the second day after birth, but a rapid and large (50-fold) induction of this gene in the ensuing neonatal period. Myoglobin expression was limited, however, to fibers located centrally within the limb which coexpress myosin isoforms characteristic of type I, IIA, and IIX fibers. This induction of myoglobin expression within the early postnatal period was accompanied by increased expression of nuclear genes encoding mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial protein expression that can be induced in adult muscle fibers by continuous motor nerve stimulation. This comparison suggests that progressive locomotor activity of neonatal animals may provide signals which trigger the development of the specialized features of oxidative, fatigue-resistant skeletal muscle fibers.

  16. COORDINATED DEVELOPMENT OF THE SARCOPLASMIC RETICULUM AND T SYSTEM DURING POSTNATAL DIFFERENTIATION OF RAT SKELETAL MUSCLE

    PubMed Central

    Schiaffino, S.; Margreth, A.

    1969-01-01

    An electron microscope study has been carried out on rat psoas muscle, during the early postnatal stages of development. Among the several subcellular components, the sarcotubular system undergoes the most striking modifications during this period. In muscle fibers of the newborn rat, junctional contacts between the T system and the SR are sparse and are, mostly, longitudinally or obliquely oriented. The T tubules do not penetrate deeply into the muscle cell, as indicated by the predominantly peripheral location of the triads and the persistence, at these stages of development, of a highly branched subsarcolemmal system of tubules. Diadic associations of junctional SR elements with the plasma membrane are also occasionally observed. The early SR elaborations incompletely delineate the myofibrils, at both the A- and I-band level. Longitudinal sections show irregularly oriented SR tubules, running continuously over successive sarcomeres. Flattened junctional cisterns filled with granular material are sparse and laterally interconnected, at circumscribed sites, with the SR tubules. Between 1 and 2 wk postpartum, transversal triadic contacts are extensively established, at the A-I band level, and the SR network differentiates into two portions in register with the A and I band, respectively. At 10–15 days after birth, the SR provides a transversely continuous double sheet around the myofibrils at the I-band level, whereas it forms a single discontinuous layer at the A-band level. The relationship that these morphological modifications of the sarcotubular system may bear to previously described biochemical and physiological changes of rat muscle fibers after birth is discussed. PMID:5814005

  17. CD44 is a Marker for the Outer Pillar Cells in the Early Postnatal Mouse Inner Ear

    PubMed Central

    Puligilla, Chandrakala; Chan, Siaw-Lin; Timothy, Caroline; Depireux, Didier A.; Ahmed, Zubair; Wolf, Jeffrey; Eisenman, David J.; Friedman, Thomas B.; Riazuddin, Sheikh; Kelley, Matthew W.; Strome, Scott E.

    2010-01-01

    Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters’ cells in the Fgfr3P244R/+ mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells. Electronic supplementary material The online version of this article (doi:10.1007/s10162

  18. Changes in fine structure of pericytes and novel desmin-immunopositive perivascular cells during postnatal development in rat anterior pituitary gland.

    PubMed

    Jindatip, Depicha; Fujiwara, Ken; Horiguchi, Kotaro; Tsukada, Takehiro; Kouki, Tom; Yashiro, Takashi

    2013-09-01

    Pericytes are perivascular cells associated with capillaries. We previously demonstrated that pericytes, identified by desmin immunohistochemistry, produce type I and III collagens in the anterior pituitary gland of adult rats. In addition, we recently used desmin immunoelectron microscopy to characterize a novel type of perivascular cell, dubbed a desmin-immunopositive perivascular cell, in the anterior pituitary. These two types of perivascular cells differ in fine structure. The present study attempted to characterize the morphological features of pituitary pericytes and novel desmin-immunopositive perivascular cells during postnatal development, in particular their role in collagen synthesis. Desmin immunostaining revealed numerous perivascular cells at postnatal day 5 (P5) and P10. Transmission electron microscopy showed differences in the fine structure of the two cell types, starting at P5. Pericytes had well-developed rough endoplasmic reticulum and Golgi apparatus at P5 and P10. The novel desmin-immunopositive perivascular cells exhibited dilated cisternae of rough endoplasmic reticulum at P5-P30. In addition, during early postnatal development in the gland, a number of type I and III collagen-expressing cells were observed, as were high expression levels of these collagen mRNAs. We conclude that pituitary pericytes and novel desmin-immunopositive perivascular cells contain well-developed cell organelles and that they actively synthesize collagens during the early postnatal period.

  19. Cortical and Subcortical Connections of V1 and V2 in Early Postnatal Macaque Monkeys

    PubMed Central

    Baldwin, Mary K.L.; Kaskan, Peter M.; Zhang, Bin; Chino, Yuzo M.; Kaas, Jon H.

    2013-01-01

    Connections of primary (V1) and secondary (V2) visual areas were revealed in macaque monkeys ranging in age from 2 to 16 weeks by injecting small amounts of cholera toxin subunit B (CTB). Cortex was flattened and cut parallel to the surface to reveal injection sites, patterns of labeled cells, and patterns of cytochrome oxidase (CO) staining. Projections from the lateral geniculate nucleus and pulvinar to V1 were present at 4 weeks of age, as were pulvinar projections to thin and thick CO stripes in V2. Injections into V1 in 4- and 8-week-old monkeys labeled neurons in V2, V3, middle temporal area (MT), and dorsolateral area (DL)/V4. Within V1 and V2, labeled neurons were densely distributed around the injection sites, but formed patches at distances away from injection sites. Injections into V2 labeled neurons in V1, V3, DL/V4, and MT of monkeys 2-, 4-, and 8-weeks of age. Injections in thin stripes of V2 preferentially labeled neurons in other V2 thin stripes and neurons in the CO blob regions of V1. A likely thick stripe injection in V2 at 4 weeks of age labeled neurons around blobs. Most labeled neurons in V1 were in superficial cortical layers after V2 injections, and in deep layers of other areas. Although these features of adult V1 and V2 connectivity were in place as early as 2 postnatal weeks, labeled cells in V1 and V2 became more restricted to preferred CO compartments after 2 weeks of age. PMID:21800316

  20. Do families after early postnatal discharge need new ways to communicate with the hospital? A feasibilility study.

    PubMed

    Danbjørg, Dorthe Boe; Wagner, Lis; Clemensen, Jane

    2014-06-01

    the length of the postnatal hospital stay in Denmark as well as globally has been radically reduced over the past 10-20 years and this raises the challenge of finding new ways of providing observation and support to families discharged early, that they otherwise would be provided as inpatients. this study is to identify the nursing support needs of new parents and their infants during the first seven days post partum, by drawing on the experiences of all stakeholders' in early postnatal discharge from hospital, and thereby gaining new knowledge to investigate further whether telemedicine is a viable option in providing the required support. this article describes the first phase of a participatory design process. A qualitative approach guided the research process and the data analysis. Data were collected from participant observation, qualitative interviews with the new parents, focus groups interviews and a workshop attended by the new parents and health-care professionals. the total number of participants in this study was 37; nineteen parents and 18 health-care professionals from one hospital and three municipalities in Denmark. the investigation findings highlighted, amongst other aspects, the importance of individualised postnatal follow-up in which families have increased access to the health-care professionals and are provided with timely information tailored to their specific needs. the present study underscored that the families experiencing early discharge were not provided with seamless individualised follow-up support. They requested more availability from the health-care system to respond to their concerns and questions during the postnatal period. They experienced a barrier in attempting to contact health-care professionals following hospital discharge and they asked for new ways to communicate that would eliminate that barrier and meet their needs for more individualised and timely information and guidance. Copyright © 2013 Elsevier Ltd. All rights

  1. Effects of Afobazole on Postnatal Development of Rat Offspring.

    PubMed

    Bugaeva, L I; Denisova, T D; Sergeeva, S A; Morozova, Yu A; Kharlamov, I V

    2017-02-01

    Physical development, development of sensory and motor reflexes, behavioral and mnestic patterns were studied infantile and juvenile rat pups born by female rats receiving Afobazole during pregnancy. Physical development and development of sensory and motor reflexes in rats were completed without pathologies by the age of 2 months. During the infantile period, the rat pups demonstrated reduced body weight gain, delayed eye opening and pupillary response formation, decreased muscle force, and suppressed motor behavior. During the juvenile period, body weight gain and development of motor behavior were intensified. Females demonstrated later vagina opening and poorer mnestic responses. In males, the terms of sexual maturation were unchanged and processes of learning and memory retrieval were not impaired.

  2. Aquaporin-4 expression contributes to decreases in brain water content during mouse postnatal development.

    PubMed

    Li, Xiumiao; Gao, Junying; Ding, Jiong; Hu, Gang; Xiao, Ming

    2013-05-01

    The water channel protein aquaporin-4 (AQP4) is implicated to facilitate water efflux from the brain parenchyma into the blood and CSF, playing a critical role in maintaining brain water homeostasis. Nevertheless, its contribution to decreases in brain water content during postnatal development remains unknown. A quantitative Western blot analysis was performed to investigate developmental expression of AQP4 in the whole mouse brain and showed that AQP4 expression level in 1 week-old brain was only 21.3% of that in the adult brain, but significantly increased to 67.4% of the adult level by 2 weeks after birth. Statistical analysis demonstrated that increased AQP4 expression partially relates to decreased brain water content in postnatal mice (r(2)=0.92 and P=0.002). Moreover, AQP4 null mice had greater brain water content than littermate controls from 2 weeks up to adult age. Consistently, mature pattern of AQP4 localization at the brain-blood and brain-CSF interfaces were completed at approximately at 2 weeks after birth. In addition, AQP4 expression in the brain stem and hypothalamus was earlier than that in the cerebral cortex and cerebellum, suggesting a brain regional variation in developmental expression of AQP4. These results characterize the developmental feature of AQP4 expression in the postnatal brain and provide direct evidence for a role of AQP4 in postnatal brain water uptake.

  3. ALDEHYDE DEHYDROGENASES EXPRESSION DURING POSTNATAL DEVELOPMENT: LIVER VS. LUNG

    EPA Science Inventory

    Aldehydes are highly reactive molecules present in the environment, and can be produced during biotransformation of xenobiotics. Although the lung can be a major target for aldehyde toxicity, development of aldehyde dehydrogenases (ALDHs), which detoxify aldehydes, in lung has be...

  4. ALDEHYDE DEHYDROGENASES EXPRESSION DURING POSTNATAL DEVELOPMENT: LIVER VS. LUNG

    EPA Science Inventory

    Aldehydes are highly reactive molecules present in the environment, and can be produced during biotransformation of xenobiotics. Although the lung can be a major target for aldehyde toxicity, development of aldehyde dehydrogenases (ALDHs), which detoxify aldehydes, in lung has be...

  5. Study of prenatal and postnatal development of spleen of Gallus Domesticus (deshi chicken).

    PubMed

    Khalil, M; Sultana, S Z; Rahman, M; Mannan, S; Ahmed, S; Ara, Z G; Sultana, Z R; Chowdhury, A I

    2009-07-01

    Spleen is one of the secondary or peripheral lymphoid organs along with cecal tonsils in birds. The growth of the spleen of Gallus Domesticus (deshi chicken) from prenatal embryonic day fifteen (ED15) to postnatal day ninety (D90) were studied. In macroscopic study it was found that the shape of the spleen was rounded with slightly flattened from side to side at its middle part at prenatal period (ED15, ED18) and becomes rounded at postnatal stages of the deshi chicken (D90). Regarding position it lies close to the right side of the junction between proventriculus and gizzard and was similar in prenatal and postnatal stages. The result of the present study revealed that the mean diameter and weight of the spleen in deshi chicken gradually increases with increase of age, which were 2.00+/-0.136mm and 0.007+/-0.00gm respectively at ED15 stage and it reaches upto 10.40+/-0.331mm and .303+/-0.004gm respectively at day 90 (D90). It was observed that the differences of diameter & weight of the spleen between different ages were statistically significant (p<0.01). Histologically the spleen was surrounded by thin capsule in prenatal life, which gradually becomes thicker in postnatal life. The splenic pulps were not differentiated into white and red pulp on 15th day of embryonic life (ED15) but they were gradually differentiated into white and red pulp in the late prenatal (ED18) and postnatal period. The growth and development of spleen at each stage of the study period were found to be significantly high. Present study indicates that chicken splenic cell population, structure and function were similar to human spleen histologically. It was also found that the chicken embryo allows easy experimental access to all the stages of the splenic development, so the present study will be helpful for experimentation on lymphoid organs and to understand pathophysiology of immunological diseases of human.

  6. Enriched and Deprived Sensory Experience Induces Structural Changes and Rewires Connectivity during the Postnatal Development of the Brain

    PubMed Central

    Bengoetxea, Harkaitz; Ortuzar, Naiara; Bulnes, Susana; Rico-Barrio, Irantzu; Lafuente, José Vicente; Argandoña, Enrike G.

    2012-01-01

    During postnatal development, sensory experience modulates cortical development, inducing numerous changes in all of the components of the cortex. Most of the cortical changes thus induced occur during the critical period, when the functional and structural properties of cortical neurons are particularly susceptible to alterations. Although the time course for experience-mediated sensory development is specific for each system, postnatal development acts as a whole, and if one cortical area is deprived of its normal sensory inputs during early stages, it will be reorganized by the nondeprived senses in a process of cross-modal plasticity that not only increases performance in the remaining senses when one is deprived, but also rewires the brain allowing the deprived cortex to process inputs from other senses and cortices, maintaining the modular configuration. This paper summarizes our current understanding of sensory systems development, focused specially in the visual system. It delineates sensory enhancement and sensory deprivation effects at both physiological and anatomical levels and describes the use of enriched environment as a tool to rewire loss of brain areas to enhance other active senses. Finally, strategies to apply restorative features in human-deprived senses are studied, discussing the beneficial and detrimental effects of cross-modal plasticity in prostheses and sensory substitution devices implantation. PMID:22848849

  7. Characterization of spinal α-adrenergic modulation of nociceptive transmission and hyperalgesia throughout postnatal development in rats

    PubMed Central

    Walker, S M; Fitzgerald, M

    2007-01-01

    Background and purpose: The selective α2-adrenergic agonist dexmedetomidine is used clinically for analgesia and sedation, but effects in early life are not well characterized. Investigation of age-related effects of dexmedetomidine is important for evaluating responses to exogenously administered analgesics and provides insight into postnatal function of noradrenergic pathways. Experimental Approach: We examined effects of epidural dexmedetomidine in anaesthetized rat pups (3, 10 and 21 postnatal days) using a quantitative model of nociception and C-fibre induced hyperalgesia. Electromyographic recordings of withdrawal responses to hindpaw mechanical stimuli measured effects of dexmedetomidine upon the baseline reflex and the response to mustard oil application on the hindpaw (primary hyperalgesia) or hindlimb (secondary hyperalgesia). In addition, we compared epidural with systemic administration, examined effects of spinal transection and evaluated heart rate changes following dexmedetomidine. Key Results: Epidural dexmedetomidine dose-dependently prevented mustard oil-induced hyperalgesia at all ages but dose requirements were lower in the youngest pups. Higher doses also suppressed the baseline nociceptive reflex when given epidurally, but had no effect when given systemically. Analgesic efficacy was the same for primary and secondary hyperalgesia, and was not diminished by spinal cord transection. Conclusions and Implications: Our laboratory studies predict that spinally mediated α2-agonist analgesia would be effective throughout postnatal development, dose requirements would be lower in early life and selective anti-hyperalgesic effects could be achieved with epidural administration at doses lower than associated with antinociceptive or cardiovascular effects. Clinical trials of α2 agonists in neonates and infants should consider developmentally regulated changes. PMID:17533423

  8. Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat.

    PubMed

    Okada, Tomoo; Takahashi, Shigeru; Nagano, Nobuhiko; Yoshikawa, Kayo; Usukura, Yukihiro; Hosono, Shigeharu

    2015-01-01

    The concept of the developmental origins of health and disease is based on studies by Barker et al. They proposed a hypothesis that undernutrition in utero permanently changes the body's structure, function, and metabolism in ways that lead to atherosclerosis and insulin resistance in later life. In addition, profound effects on the extent of body fatness and insulin sensitivity are demonstrated, if there is a "mismatch" between prenatal and postnatal environments. In previous studies, undernutrition in utero has been evaluated simply by birth weight itself or birth weight for gestational age, and the degree of mismatch has been estimated by postnatal rapid weight gain. Recently, we investigated subcutaneous fat accumulation in small-for-gestational-age infants and found that a rapid catch-up in skinfold thickness developed prior to the body weight catch-up. Furthermore, insulin-like growth factor-I and lipoprotein lipase mass concentrations also demonstrate rapid increase during the neonatal period with fat accumulation. Investigating the precise mechanisms of developmental origins of health and disease including mediating metabolic and hormonal factors may provide a new approach to prevent atherosclerosis and insulin resistance. Better management of undernutrition during gestation and neonatal growth during the early postnatal period is an important theme for future health.

  9. Compound equation developed for postnatal growth of birds and mammals

    NASA Technical Reports Server (NTRS)

    Laird, A. K.

    1968-01-01

    Compound growth equation was developed in which the rate of this linear growth process is regarded as proportional to the mass already attained at any instant by an underlying Gompertz process. This compound growth model was fitted to the growth data of a variety of birds and mammals of both sexes.

  10. [Postnatal development of sensory nerve endings in the hairless nose skin of the cat].

    PubMed

    Halata, Z

    1981-01-01

    The postnatal development of sensory nerve endings has been studied in the skin of the planum nasale of the cat. The Merkel nerve endings develop in the prenatal period; after birth some redundant axons perish. Up to the third postnatal day, sporadic Merkel cells and nerve terminals still can be observed in the stratum papillare of the dermis. The free nerve endings in the dermis appear before birth. In the postnatal period the nerve fibres as well as the nerve endings ramify. A few of them come into contact with the stratum basale of the epidermis, others may perish. Most of these nerve endings are located in the stratum papillare of the dermis. The simple encapsulated corpuscles with an inner core develop after birth. In the depth of the dermis, the corpuscles are arranged mainly in groups, in the stratum papillare, however, they are more isolated. The development of those corpuscles, located in the depth of the dermis, already begins before birth and finishes mostly about the 39th postnatal day. The development of the corpuscles in the stratum papillare starts later and ends between the 3rd and 4th month. The nerve terminal of the corpuscle changes only slightly during development. It elongates, becomes thicker, and the number of mitochondria increases. During all stages it sends cytoplasmic spines in between the lamellar system of the inner core. The inner core is formed by cytoplasmic lamellae of the peripheric glial cells. In the course of development the number of cytoplasmic lamellae increases, they become thinner and gradually each one will be covered by a basal lamina. A mature corpuscle possesses an inner core with one or two longitudinal clefts. These clefts occur more frequently in corpuscles with complete capsules. The connective tissue cells primarily form a primitive capsule around the inner core. During development the layers of the capsule increase in number. Mature corpuscles have a one- to four-layered capsule. The capsular cells are then

  11. Tiny moments of great importance: the Marte Meo method applied in the context of early mother-infant interaction and postnatal depression. Utilizing Daniel Stern's theory of 'schemas of being with' in understanding empirical findings and developing a stringent Marte Meo methodology.

    PubMed

    Vik, Kari; Rohde, Rolf

    2014-01-01

    This paper provides an overview of basic Marte Meo video interaction guidance concepts and describes the therapeutic performance of the method applied in the context of early mother-infant interaction and postnatal depression. Weight is put upon the importance of the therapeutic relationship. Further Marte Meo therapy is understood in the light of Daniel Stern's theory of 'schemas of being with' and accompanied by clinical vignettes from therapy sessions. The empirical basis for the paper is a study of postnatal depression, mother-infant interaction and video guidance, carried out in Southern Norway. The study examined Marte Meo from a phenomenological perspective. Marte Meo was offered to mothers with either postnatal depression or depressive symptoms. In in-depth interviews the participants reported that the Marte Meo method, 'from the outside looking in', increased their reflections about their infants and their own mental states as well as their sensitive interaction with their newborn. Their mothering was improved and they reported feeling less depressed. We argue that Marte Meo methodology can guide new mothers with depressive symptoms, and contribute to the creation of new schemas of being together.

  12. Phospholipase D Family Member 4, a Transmembrane Glycoprotein with No Phospholipase D Activity, Expression in Spleen and Early Postnatal Microglia

    PubMed Central

    Yoshikawa, Fumio; Banno, Yoshiko; Otani, Yoshinori; Yamaguchi, Yoshihide; Nagakura-Takagi, Yuko; Morita, Noriyuki; Sato, Yumi; Saruta, Chihiro; Nishibe, Hirozumi; Sadakata, Tetsushi; Shinoda, Yo; Hayashi, Kanehiro; Mishima, Yuriko; Baba, Hiroko; Furuichi, Teiichi

    2010-01-01

    -carrying, transmembrane glycoprotein localized in the endoplasmic reticulum and Golgi apparatus. The spatiotemporally restricted expression patterns suggested that PLD4 might play a role in common function(s) among microglia during early postnatal brain development and splenic marginal zone cells. PMID:21085684

  13. Postnatal development attunes olfactory bulb mitral cells to high-frequency signaling.

    PubMed

    Yu, Yiyi; Burton, Shawn D; Tripathy, Shreejoy J; Urban, Nathaniel N

    2015-11-01

    Mitral cells (MCs) are a major class of principal neurons in the vertebrate olfactory bulb, conveying odor-evoked activity from the peripheral sensory neurons to olfactory cortex. Previous work has described the development of MC morphology and connectivity during the first few weeks of postnatal development. However, little is known about the postnatal development of MC intrinsic biophysical properties. To understand stimulus encoding in the developing olfactory bulb, we have therefore examined the development of MC intrinsic biophysical properties in acute slices from postnatal day (P)7-P35 mice. Across development, we observed systematic changes in passive membrane properties and action potential waveforms consistent with a developmental increase in sodium and potassium conductances. We further observed developmental decreases in hyperpolarization-evoked membrane potential sag and firing regularity, extending recent links between MC sag heterogeneity and firing patterns. We then applied a novel combination of statistical analyses to examine how the evolution of these intrinsic biophysical properties specifically influenced the representation of fluctuating stimuli by MCs. We found that immature MCs responded to frozen fluctuating stimuli with lower firing rates, lower spike-time reliability, and lower between-cell spike-time correlations than more mature MCs. Analysis of spike-triggered averages revealed that these changes in spike timing were driven by a developmental shift from broad integration of inputs to more selective detection of coincident inputs. Consistent with this shift, generalized linear model fits to MC firing responses demonstrated an enhanced encoding of high-frequency stimulus features by mature MCs.

  14. Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia–Ischemia

    PubMed Central

    Jantzie, Lauren L.; Corbett, Christopher J.; Firl, Daniel J.; Robinson, Shenandoah

    2015-01-01

    Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia–ischemia (TSHI) in Sprague–Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants. PMID:24722771

  15. Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia-Ischemia.

    PubMed

    Jantzie, Lauren L; Corbett, Christopher J; Firl, Daniel J; Robinson, Shenandoah

    2015-09-01

    Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) in Sprague-Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants.

  16. The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor cells.

    PubMed

    Homman-Ludiye, Jihane; Merson, Tobias D; Bourne, James A

    2012-01-01

    The postnatal neocortex has traditionally been considered a non-neurogenic region, under non-pathological conditions. A few studies suggest, however, that a small subpopulation of neural cells born during postnatal life can differentiate into neurons that take up residence within the neocortex, implying that postnatal neurogenesis could occur in this region, albeit at a low level. Evidence to support this hypothesis remains controversial while the source of putative neural progenitors responsible for generating new neurons in the postnatal neocortex is unknown. Here we report the identification of self-renewing multipotent neural progenitor cells (NPCs) derived from the postnatal day 14 (PD14) marmoset monkey primary visual cortex (V1, striate cortex). While neuronal maturation within V1 is well advanced by PD14, we observed cells throughout this region that co-expressed Sox2 and Ki67, defining a population of resident proliferating progenitor cells. When cultured at low density in the presence of epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF-2), dissociated V1 tissue gave rise to multipotent neurospheres that exhibited the ability to differentiate into neurons, oligodendrocytes and astrocytes. While the capacity to generate neurones and oligodendrocytes was not observed beyond the third passage, astrocyte-restricted neurospheres could be maintained for up to 6 passages. This study provides the first direct evidence for the existence of multipotent NPCs within the postnatal neocortex of the nonhuman primate. The potential contribution of neocortical NPCs to neural repair following injury raises exciting new possibilities for the field of regenerative medicine.

  17. Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The 'EDEN mother-child' cohort (study of pre- and early postnatal determinants of the child's development and health)

    PubMed Central

    Drouillet, Peggy; Forhan, Anne; De Lauzon-Guillain, Blandine; Thiébaugeorges, Olivier; Goua, Valérie; Magnin, Guillaume; Schweitzer, Michel; Kaminski, Monique; Ducimetière, Pierre; Charles, Marie-Aline

    2009-01-01

    Background Recent studies suggest a benefit of seafood and n-3 Fatty Acids (FA) intake on fetal growth and infant development. Objectives To study the association between FA intake and fetal growth in French pregnant women. Design Pregnant women included in the EDEN mother-child cohort study answered food frequency questionnaires on their usual diet 1) in the year prior to pregnancy and 2) during the last three months of pregnancy (n=1439). Conversion into nutrient intakes was performed using data on portion size and a French food composition table. Associations between maternal FA intakes and several neonatal anthropometric measurements were studied using linear regressions adjusted for center, mother’s age, smoking habits, height, parity, gestational age and newborn’s sex. Due to significant interaction, analyses were stratified according to maternal pre-pregnancy overweight status. Results Neither total lipid nor saturated, monounsaturated or polyunsaturated (PUFA) fat intake were significantly associated with newborn size. In overweight women only (n=366), a high pre-pregnancy n-3FA intake (% n-3FA/PUFA) was positively associated with newborn’s birthweight (p=0.01), head, arm and wrist circumferences and sum of skinfolds (p<0.04). A substitution of one percent of n-3FA per day before pregnancy by other PUFA was related to an average decrease in birthweight of 60 g (p=0.01). Relationships with n-3FA intake at the end of pregnancy were weaker and not significant. Conclusions A high pre-pregnancy ratio n-3FA/PUFA may sustain fetal growth in overweight women. Follow-up of the children may help determine whether this has beneficial consequences for the child’s health and development. PMID:18631416

  18. Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The 'EDEN mother-child' cohort (study of pre- and early postnatal determinants of the child's development and health).

    PubMed

    Drouillet, Peggy; Forhan, Anne; De Lauzon-Guillain, Blandine; Thiébaugeorges, Olivier; Goua, Valérie; Magnin, Guillaume; Schweitzer, Michel; Kaminski, Monique; Ducimetière, Pierre; Charles, Marie-Aline

    2009-02-01

    Recent studies suggest a benefit of seafood and n-3 fatty acid intake on fetal growth and infant development. The objective was to study the association between fatty acid intake and fetal growth in pregnant French women. Pregnant women included in the EDEN mother-child cohort study completed FFQ on their usual diet: (1) in the year before pregnancy and (2) during the last 3 months of pregnancy (n 1439). Conversion into nutrient intakes was performed using data on portion size and a French food composition table. Associations between maternal fatty acid intakes and several neonatal anthropometric measurements were studied using linear regressions adjusted for centre, mother's age, smoking habits, height, parity, gestational age and newborn's sex. Due to significant interaction, analyses were stratified according to maternal pre-pregnancy overweight status. Neither total lipid nor SFA, MUFA or PUFA intake was significantly associated with newborn size. In overweight women only (n 366), a high pre-pregnancy n-3 fatty acid intake (% PUFA) was positively associated with the newborn's birth weight (P=0.01), head, arm and wrist circumferences and sum of skinfolds (P<0.04). A substitution of 1% of n-3 fatty acids per d before pregnancy by other PUFA was related to an average decrease in birth weight of 60 g (P=0.01). Relationships with n-3 fatty acid intake at the end of pregnancy were weaker and not significant. We concluded that a high pre-pregnancy n-3 fatty acid:PUFA ratio may sustain fetal growth in overweight women. Follow-up of the children may help determine whether this has beneficial consequences for the child's health and development.

  19. The vitamin C transporter SVCT2 is down-regulated during postnatal development of slow skeletal muscles.

    PubMed

    Sandoval, Daniel; Ojeda, Jorge; Low, Marcela; Nualart, Francisco; Marcellini, Sylvain; Osses, Nelson; Henríquez, Juan Pablo

    2013-06-01

    Vitamin C plays key roles in cell homeostasis, acting as a potent antioxidant as well as a positive modulator of cell differentiation. In skeletal muscle, the vitamin C/sodium co-transporter SVCT2 is preferentially expressed in oxidative slow fibers. Besides, SVCT2 is up-regulated upon the early fusion of primary myoblasts. However, our knowledge of the postnatal expression profile of SVCT2 remains scarce. Here we have analyzed the expression of SVCT2 during postnatal development of the chicken slow anterior and fast posterior latissimus dorsi muscles, ranging from day 7 to adulthood. SVCT2 expression is consistently higher in the slow than in the fast muscle at all stages. After hatching, SVCT2 expression is significantly down-regulated in the anterior latissimus dorsi, which nevertheless maintains a robust slow phenotype. Taking advantage of the C2C12 cell line to recapitulate myogenesis, we confirmed that SVCT2 is expressed in a biphasic fashion, reaching maximal levels upon early myoblasts fusion and decreasing during myotube growth. Together, these findings suggest that the dynamic expression levels of SVCT2 could be relevant for different features of skeletal muscle physiology, such as muscle cell formation, growth and activity.

  20. Early postnatal GFAP-expressing cells produce multilineage progeny in cerebrum and astrocytes in cerebellum of adult mice.

    PubMed

    Guo, Zhibao; Wang, Xijuan; Xiao, Jun; Wang, Yihui; Lu, Hong; Teng, Junfang; Wang, Wei

    2013-09-26

    Early postnatal GFAP-expressing cells are thought to be immature astrocytes. However, it is not clear if they possess multilineage capacity and if they can generate different lineages (astrocytes, neurons and oligodendrocytes) in the brain of adult mice. In order to identify the fate of astroglial cells in the postnatal brain, hGFAP-Cre-ER(T2) transgenic mice were crossed with the R26R Cre reporter mouse strains which exhibit constitutive expression of β-galactosidase (β-gal). Mice carrying the hGFAP-Cre-ER(T2)/R26R transgene were treated with Tamoxifen to induce Cre recombination in astroglial cells at postnatal (P) day 6 and Cre recombinase-expressing cells were identified by X-gal staining. Immunohistochemical staining was used to identify the type(s) of these reporter-tagged cells. Sixty days after recombination, X-gal-positive cells in different cerebral regions of the adult mice expressed the astroglial markers Blbp and GFAP, the neuronal marker NeuN, the oligodendrocyte precursor cell marker NG2 and the mature oligodendrocyte marker CC1. X-gal-positive cells in the cerebellum coexpressed the astroglial marker Blbp, but not the granule cell marker NeuN, Purkinje cell marker Calbindin or oligodendrocyte precursor cell marker NG2. Our genetic fate mapping data demonstrated that early postnatal GFAP-positive cells possessed multilineage potential and eventually differentiated into neurons, astrocytes, and oligodendrocyte precursor cells in the cerebrum and into astrocytes (including Bergmann glia) in the cerebellum of adult mice.

  1. Postnatal foraging demands alter adrenocortical activity and psychosocial development.

    PubMed

    Lyons, D M; Kim, S; Schatzberg, A F; Levine, S

    1998-05-01

    Mother squirrel monkeys stop carrying infants at earlier ages in high-demand (HD) conditions where food is difficult to find relative to low-demand (LD) conditions. To characterize these transitions in psychosocial development, from 10- to 21-weeks postpartum we collected measures of behavior, adrenocortical activity, and social transactions coded for initiator (mother or infant), goal (make-contact or break-contact), and outcome (success or failure). Make-contact attempts were most often initiated by HD infants, but mothers often opposed these attempts and less than 50% were successful. Break-contact attempts were most often initiated by LD infants, but mothers often opposed these attempts and fewer LD than HD infant break-contact attempts were successful. Plasma levels of cortisol were significantly higher in HD than LD mothers, but differences in adrenocortical activity were less consistent in their infants. HD and LD infants also spent similar amounts of time nursing on their mothers and feeding on solid foods. By rescheduling some transitions in development (carry-->self-transport), and not others (nursing-->self-feeding), mothers may have partially protected infants from the immediate impact of an otherwise stressful foraging task.

  2. Expression of macrophage migration inhibitory factor in the mouse neocortex and posterior piriform cortices during postnatal development.

    PubMed

    Zhang, Wei; Li, Lingling; Wang, Jiutao; An, Lei; Hu, Xinde; Xie, Jiongfang; Yan, Runchuan; Chen, Shulin; Zhao, Shanting

    2014-11-01

    Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in a vast array of cellular and biological processes. Abnormal expression of MIF has been implicated in many neurological diseases, including Parkinson's disease, epilepsy, Alzheimer's Disease, stroke, and neuropathic pain. However, the expression patterns of mif transcript and MIF protein from the early postnatal period through adulthood in the mouse brain are still poorly understood. We therefore investigated the temporal and spatial expression of MIF in the mouse neocortex during postnatal development in detail and partially in posterior piriform cortices (pPC). As determined by quantitative real-time PCR (qPCR), mif transcript gradually increased during development, with the highest level noted at postnatal day 30 (P30) followed by a sharp decline at P75. In contrast, Western blotting results showed that MIF increased constantly from P7 to P75. The highest level of MIF was at P75, while the lowest level of MIF was at P7. Immunofluorescence histochemistry revealed that MIF-immunoreactive (ir) cells were within the entire depth of the developed neocortex, and MIF was heterogeneously distributed among cortical cells, especially at P7, P14, P30, and P75; MIF was abundant in the pyramidal layer within pPC. Double immunostaining showed that all the mature neurons were MIF-ir and all the intensely stained MIF-ir cells were parvalbumin positive (Pv +) at adult. Moreover, it was demonstrated that MIF protein localized in the perikaryon, processes, presynaptic structures, and the nucleus in neurons. Taken together, the developmentally regulated expression and the subcellular localization of MIF should form a platform for an analysis of MIF neurodevelopmental biology and MIF-related nerve diseases.

  3. Postnatal development of nestin positive neurons in rat basal forebrain: different onset and topography with choline acetyltransferase and parvalbumin expression.

    PubMed

    Guo, Kai-Hua; Li, Dong-Pei; Gu, Huai-Yu; Jie-Xu; Yao, Zhi-Bin

    2014-06-01

    Our previous studies identified a sub-population of cholinergic neurons which express nestin in the rostral part of the basal forebrain (BF) in normal adult rats. In the present study, the postnatal developmental patterns of nestin, choline acetyl transferase (ChAT) and parvalbumin (PV) positive neurons were explored by means of immunohistochemistry combined with immunofluorescence double label methods. Compared with early onset of ChAT expression (from P1) and delayed onset of PV expression (from P16), nestin positive activity was detected in the BF from P9 and co-expressed by parts of the ChAT positive neurons within the same region during the whole postnatal development process. However, ChAT and PV were not coexpressed by the neurons within the medial septum-diagonal band of Broca (MS-DBB) of BF. These results might imply a composite of separate development patterns displayed by different subpopulations of cholinergic neurons (nestin positive cholinergic neurons and nestin negative cholinergic neurons) within this region. Moreover, the topographic distribution of nestin, ChAT and PV positive neurons also showed different characteristics. In summary, our present study revealed a remarkable timing and topographic difference on the postnatal development of the nestin expression within the MS-DBB of BF compared with ChAT and PV expression. It is further suggested that nestin is re-expressed by cholinergic neurons in the BF after differentiation but not persisted from neuronal precursor cells. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  4. Cross-fostering effect on postnatal development of rat pups exposed to methamphetamine during gestation and preweaning periods.

    PubMed

    Pometlová, Marie; Hrubá, Lenka; Slamberová, Romana; Rokyta, Richard

    2009-04-01

    There are studies showing that drug abuse during pregnancy may have a long-term effect on progeny of drug-abusing mothers. Our previous work demonstrated that prenatal and/or postnatal methamphetamine injections impair maternal behavior. The purpose of the present study was to assess the effect of prenatal methamphetamine or stress exposure and postnatal breeding on postnatal development of rat pups. Female rats were injected with methamphetamine (5 mg/kg daily) or physiological saline prior, during and after gestation. Absolute controls did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received some of her own and some of the pups from the mothers with the other two treatments. Pups were weighted daily for the entire lactation period. Postural motor reaction development was examined daily by righting reflex between postnatal day 1 and 12. On postnatal day 15 homing test examining pups' nest-seeking behavior was performed. On postnatal day 23 rotarod and bar-holding tests were used to investigate sensorimotor coordination of pups. We demonstrated that prenatal methamphetamine exposure impairs performance of sensorimotor tests (righting reflex on surface and rotarod test). Moreover, the effect of methamphetamine as well as the effect of prenatal stress induced by saline injections was affected by postnatal breeding conditions in sensorimotor tests as well as in the test of homing. Our results support the hypothesis that the variation in rat maternal care could serve as a mechanism for a nongenomic behavioral mode of transmission of traits.

  5. Early leptin intervention reverses perturbed energy balance regulating hypothalamic neuropeptides in the pre- and postnatal calorie-restricted female rat offspring.

    PubMed

    Gibson, Leena Caroline; Shin, Bo-Chul; Dai, Yun; Freije, William; Kositamongkol, Sudatip; Cho, John; Devaskar, Sherin U

    2015-06-01

    Pre- and postnatal calorie restriction is associated with postnatal growth restriction, reduced circulating leptin concentrations, and perturbed energy balance. Hypothalamic regulation of energy balance demonstrates enhanced orexigenic (NPY, AgRP) and diminished anorexigenic (POMC, CART) neuropeptide expression (PN21), setting the stage for subsequent development of obesity in female Sprague-Dawley rats. Leptin replenishment during the early postnatal period (PN2-PN8) led to reversal of the hypothalamic orexigenic:anorexigenic neuropeptide ratio at PN21 by reducing only the orexigenic (NPY, AgRP), without affecting the anorexigenic (POMC, CART) neuropeptide expression. This hypothalamic effect was mediated via enhanced leptin receptor (ObRb) signaling that involved increased pSTAT3/STAT3 but reduced PTP1B. This was further confirmed by an increase in body weight at PN21 in response to intracerebroventricular administration of antisense ObRb oligonucleotides (PN2-PN8). The change in the hypothalamic neuropeptide balance in response to leptin administration was associated with increased oxygen consumption, carbon dioxide production, and physical activity, which resulted in increased milk intake (PN14) with no change in body weight. This is in contrast to the reduction in milk intake with no effect on energy expenditure and physical activity observed in controls. We conclude that pre- and postnatal calorie restriction perturbs hypothalamic neuropeptide regulation of energy balance, setting the stage for hyperphagia and reduced energy expenditure, hallmarks of obesity. Leptin in turn reverses this phenotype by increasing hypothalamic ObRb signaling (sensitivity) and affecting only the orexigenic arm of the neuropeptide balance. © 2015 Wiley Periodicals, Inc.

  6. Postnatal development of collagen structure in ovine articular cartilage

    PubMed Central

    2010-01-01

    Background Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly parallel to the articular surface near the articular surface. Recent studies into collagen fibre orientation in stillborn and juvenile animals showed that this structure is absent at birth. Since the collagen structure is an important factor for AC mechanics, the absence of the adult Benninghoff structure has implications for perinatal AC mechanobiology. The current objective is to quantify the dynamics of collagen network development in a model animal from birth to maturity. We further aim to show the presence or absence of zonal differentiation at birth, and to assess differences in collagen network development between different anatomical sites of a single joint surface. We use quantitative polarised light microscopy to investigate properties of the collagen network and we use the sheep (Ovis aries) as our model animal. Results Predominant collagen orientation is parallel to the articular surface throughout the tissue depth for perinatal cartilage. This remodels to the Benninghoff structure before the sheep reach sexual maturity. Remodelling of predominant collagen orientation starts at a depth just below the future transitional zone. Tissue retardance shows a minimum near the articular surface at all ages, which indicates the presence of zonal differentiation at all ages. The absolute position of this minimum does change between birth and maturity. Between different anatomical sites, we find differences in the dynamics of collagen remodelling, but no differences in adult collagen structure. Conclusions The collagen network in articular cartilage remodels between birth and sexual maturity from a network with predominant orientation parallel to the articular surface to a

  7. Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure.

    PubMed

    Legrand, M; Elie, C; Stefani, J; N Florès; Culeux, C; Delissen, O; Ibanez, C; Lestaevel, P; Eriksson, P; Dinocourt, C

    2016-01-01

    The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40mg/L and 120mg/L and of GD18 fetuses exposed at 120mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120mg/L DU, but not at PND0 and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network.

  8. MicroRNAome of Porcine Pre- and Postnatal Development

    PubMed Central

    Gu, Yiren; Zhang, Kai; Lang, Qiulei; Chen, Lei; Guan, Jiuqiang; Luo, Zonggang; Chen, Haosi; Li, Yang; Li, Qinghai; Li, Xiang; Jiang, An-an; Shuai, Surong; Wang, Jinyong; Zhu, Qi; Zhou, Xiaochuan; Gao, Xiaolian; Li, Xuewei

    2010-01-01

    The domestic pig is of enormous agricultural significance and valuable models for many human diseases. Information concerning the pig microRNAome (miRNAome) has been long overdue and elucidation of this information will permit an atlas of microRNA (miRNA) regulation functions and networks to be constructed. Here we performed a comprehensive search for porcine miRNAs on ten small RNA sequencing libraries prepared from a mixture of tissues obtained during the entire pig lifetime, from the fetal period through adulthood. The sequencing results were analyzed using mammalian miRNAs, the precursor hairpins (pre-miRNAs) and the first release of the high-coverage porcine genome assembly (Sscrofa9, April 2009) and the available expressed sequence tag (EST) sequences. Our results extend the repertoire of pig miRNAome to 867 pre-miRNAs (623 with genomic coordinates) encoding for 1,004 miRNAs, of which 777 are unique. We preformed real-time quantitative PCR (q-PCR) experiments for selected 30 miRNAs in 47 tissue-specific samples and found agreement between the sequencing and q-PCR data. This broad survey provides detailed information about multiple variants of mature sequences, precursors, chromosomal organization, development-specific expression, and conservation patterns. Our data mining produced a broad view of the pig miRNAome, consisting of miRNAs and isomiRs and a wealth of information of pig miRNA characteristics. These results are prelude to the advancement in pig biology as well the use of pigs as model organism for human biological and biomedical studies. PMID:20634961

  9. Effects of microgravity on myogenic factor expressions during postnatal development of rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Inobe, Manabu; Inobe, Ikuko; Adams, Gregory R.; Baldwin, Kenneth M.; Takeda, Shin'Ichi

    2002-01-01

    To clarify the role of gravity in the postnatal development of skeletal muscle, we exposed neonatal rats at 7 days of age to microgravity. After 16 days of spaceflight, tibialis anterior, plantaris, medial gastrocnemius, and soleus muscles were removed from the hindlimb musculature and examined for the expression of MyoD-family transcription factors such as MyoD, myogenin, and MRF4. For this purpose, we established a unique semiquantitative method, based on RT-PCR, using specific primers tagged with infrared fluorescence. The relative expression of MyoD in the tibialis anterior and plantaris muscles and that of myogenin in the plantaris and soleus muscles were significantly reduced (P < 0.001) in the flight animals. In contrast, MRF4 expression was not changed in any muscle. These results suggest that MyoD and myogenin, but not MRF4, are sensitive to gravity-related stimuli in some skeletal muscles during postnatal development.

  10. Effects of microgravity on myogenic factor expressions during postnatal development of rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Inobe, Manabu; Inobe, Ikuko; Adams, Gregory R.; Baldwin, Kenneth M.; Takeda, Shin'Ichi

    2002-01-01

    To clarify the role of gravity in the postnatal development of skeletal muscle, we exposed neonatal rats at 7 days of age to microgravity. After 16 days of spaceflight, tibialis anterior, plantaris, medial gastrocnemius, and soleus muscles were removed from the hindlimb musculature and examined for the expression of MyoD-family transcription factors such as MyoD, myogenin, and MRF4. For this purpose, we established a unique semiquantitative method, based on RT-PCR, using specific primers tagged with infrared fluorescence. The relative expression of MyoD in the tibialis anterior and plantaris muscles and that of myogenin in the plantaris and soleus muscles were significantly reduced (P < 0.001) in the flight animals. In contrast, MRF4 expression was not changed in any muscle. These results suggest that MyoD and myogenin, but not MRF4, are sensitive to gravity-related stimuli in some skeletal muscles during postnatal development.

  11. Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development.

    PubMed

    Badri, Mohammed K; Zhang, Honghao; Ohyama, Yoshio; Venkitapathi, Sundharamani; Kamiya, Nobuhiro; Takeda, Haruko; Ray, Manas; Scott, Greg; Tsuji, Takehito; Kunieda, Tetsuo; Mishina, Yuji; Mochida, Yoshiyuki

    2016-08-01

    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ∼20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Ellis van Creveld2 is required for postnatal craniofacial bone development

    PubMed Central

    Badri, Mohammed K.; Zhang, Honghao; Ohyama, Yoshio; Venkitapathi, Sundharamani; Kamiya, Nobuhiro; Takeda, Haruko; Ray, Manas; Scott, Greg; Tsuji, Takehito; Kunieda, Tetsuo; Mishina, Yuji; Mochida, Yoshiyuki

    2016-01-01

    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3- and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ~20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. PMID:27090777

  13. Effect of ozone on the postnatal development of lamb mucociliary apparatus

    SciTech Connect

    Mariassy, A.T.; Abraham, W.M.; Phipps, R.J.; Sielczak, M.W.; Wanner, A. )

    1990-06-01

    We determined whether exposure to O3 early in the postnatal period impairs the normal development of the mucociliary apparatus in lambs and whether such changes lead to prolonged abnormalities in mucociliary function. Lambs were exposed to air (controls) or to 1 ppm O3 for 4 h/day for 5 days during the 1st wk of life. Tracheal mucus velocity (TMV), a marker of lung mucociliary clearance, was measured in vivo at birth (0 wk) and up to 24 wk later, and tracheal secretory function was measured (in vitro) and the morphology of the tracheal mucosa was determined at 0 and 2 wk in both groups. In the control group, TMV increased 94% from 0 to 2 wk (P less than 0.05), continued to increase until reaching a plateau at 8 wk, and then remained constant from 8 to 24 wk. In contrast, O3-exposed lambs showed a 24% decrease in TMV from 0 to 2 wk (P less than 0.05 vs. control), and throughout the remaining time TMV remained below (P less than 0.05) that observed in control lambs. O3 exposure partially prevented the age-dependent decrease in basal secretion of tracheal macromolecules normally observed between 0 and 2 wk. These changes in secretory function were associated with a significant increase in tissue conductance (37%, P less than 0.05 vs. 0 wk), predominantly the result of active chloride secretion. The functional changes induced by O3 were associated with a retardation of the normal morphological development of the tracheal epithelium.

  14. Post-natal development of the electromotor system in a pulse gymnotid electric fish.

    PubMed

    Pereira, Ana Carolina; Rodríguez-Cattaneo, Alejo; Castelló, María E; Caputi, Angel A

    2007-03-01

    Some fish emit electric fields generated by the coordinated activation of electric organs. Such discharges are used for exploring the environment and for communication. This article deals with the development of the electric organ and its discharge in Gymnotus, a pulse genus in which brief discharges are separated by regular silent intervals. It is focused on the anatomo-functional study of fish sized between 10 and 300 mm from the species of Gymnotus, in which electrogenic mechanisms are best known. It was shown that: (1) electroreception and electromotor control is present from early larval stages; (2) there is a single electric organ from larval to adult stages; (3) pacemaker rhythmicity becomes similar to that of the adult when the body length becomes greater than 45 mm and (4) there is a consistent developmental profile of the electric organ discharge in which waveform components are added according to a programmed sequence. The analysis of these data allowed us to identify three main periods in post-natal development of electrogenesis: (1) before fish reach 55 mm in length, when maturation of neural structures is the main factor determining a characteristic sequence of changes observed in the discharge timing and waveform; (2) between 55 and 100 mm in length, when peripheral maturation of the effector cells and changes in post-effector mechanisms due to the fish's growth determine minor changes in waveform and the increase in amplitude of the discharge and (3) beyond 100 mm in length, when homothetic growth of the fish body explains the continuous increase in electric power of the discharge.

  15. Tooth-bone morphogenesis during postnatal stages of mouse first molar development.

    PubMed

    Lungová, Vlasta; Radlanski, Ralf J; Tucker, Abigail S; Renz, Herbert; Míšek, Ivan; Matalová, Eva

    2011-06-01

    The first mouse molar (M1) is the most common model for odontogenesis, with research particularly focused on prenatal development. However, the functional dentition forms postnatally, when the histogenesis and morphogenesis of the tooth is completed, the roots form and the tooth physically anchors into the jaw. In this work, M1 was studied from birth to eruption, assessing morphogenesis, proliferation and apoptosis, and correlating these with remodeling of the surrounding bony tissue. The M1 completed crown formation between postnatal (P) days 0-2, and the development of the tooth root was initiated at P4. From P2 until P12, cell proliferation in the dental epithelium reduced and shifted downward to the apical region of the forming root. In contrast, proliferation was maintained or increased in the mesenchymal cells of the dental follicle. At later stages, before tooth eruption (P20), cell proliferation suddenly ceased. This withdrawal from the cell cycle correlated with tooth mineralization and mesenchymal differentiation. Apoptosis was observed during all stages of M1 postnatal morphogenesis, playing a role in the removal of cells such as osteoblasts in the mandibular region and working together with osteoclasts to remodel the bone around the developing tooth. At more advanced developmental stages, apoptotic cells and bodies accumulated in the cell layers above the tooth cusps, in the path of eruption. Three-dimensional reconstruction of the developing postnatal tooth and bone indicates that the alveolar crypts form by resorption underneath the primordia, whereas the ridges form by active bone growth between the teeth and roots to form a functional complex.

  16. Ciliogenesis in normal human kidney development and post-natal life.

    PubMed

    Saraga-Babić, Mirna; Vukojević, Katarina; Bočina, Ivana; Drnašin, Kristina; Saraga, Marijan

    2012-01-01

    Ciliogenesis in developing and post-natal human kidneys appears to influence cell proliferation and differentiation, apico-basal cell polarity, and tubular lumen formation. We have analyzed the appearance of primary cilia and differentiation of kidney cells in ten human conceptuses aged 6-22 weeks and in one 5-year-old kidney, using a double immunofluorescence labeling technique for α-tubulin, γ-tubulin, Oct-4, and Ki-67 and by electron microscopy. Immature forms of nephrons and ampullae were characterized by intense cell proliferation, which subsequently decreased during development. Primary cilia appeared on the surfaces of non-proliferating cells in developing nephrons, gradually increasing in length from 0.59 μm in renal vesicles to 0.81 μm in the S-forms of nephrons, ultimately reaching 3.04 μm in length in mature fetal and post-natal nephrons. Ciliary length increased from 0.59 μm in ampullae to 1.28 μm in post-natal collecting tubules. Mesenchymal to epithelial transformation of kidney cells coincided with the appearance of apico-basal polarity, both gap and tight junctions, and lumen formation. Up-regulation of Oct-4 expression correlated with the onset of kidney cell differentiation. Our results demonstrate the importance of proper primary cilia lengthening and Oct-4 expression for the normal development of fetal and post-natal kidneys and of apico-basal polarity for normal tubular lumen formation. Disturbances in these processes are associated with ciliopathies.

  17. Quantitative changes of nitrergic neurons during postnatal development of chicken myenteric plexus*

    PubMed Central

    Yang, Ping; Gandahi, Jameel Ahmed; Zhang, Qian; Zhang, Lin-li; Bian, Xun-guang; Wu, Li; Liu, Yi; Chen, Qiu-sheng

    2013-01-01

    Objective: Information regarding the development of the enteric nervous system (ENS) is important for understanding the functional abnormalities of the gut. Because fertilized chicken eggs provide easy access to embryos, chicken models have been widely used to study embryonic development of myenteric plexus; however, no study has been focused on the postnatal period. The aim of this study was to perform a qualitative and quantitative analysis of the nitrergic neurons in the myenteric plexus of developing chickens in the postnatal period. Methods: Whole-mount preparations of the myenteric plexus were made in 7-d, 15-d, and 40-d old (adult) chickens of either sex (n=15). The myenteric plexus was studied after nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry using light microscopy, digital photography, and Image-Pro Plus 6.0 software. The numbers of positively stained neurons and ganglia were counted in the duodenum, jejunum, ileum, caecum, and colon in the different age groups. Data were expressed as mean±standard deviation (SD), and statistical analysis was performed using a one-way analysis of variance (ANOVA) test. Results: The positively stained neurons showed various morphologies and staining intensities, and formed bead-shaped and U-shaped arrangements in the myenteric plexus. The densities of neurons and ganglia increased with age. However, the number of positive neurons per ganglion increased. The number of NADPH-d-positive neurons was highest in the colon, followed by the ileum, the jejunum, the duodenum, and the caeca in all age groups. Conclusions: Developmental changes in the myenteric plexus of chickens continue in the postnatal period, indicating that the maturation process of the gastrointestinal function is gradual. In addition, no significant difference is happening among different intestinal segments during postnatal development, suggesting that the function of different intestinal segments had been determined after

  18. Tooth-bone morphogenesis during postnatal stages of mouse first molar development

    PubMed Central

    Lungová, Vlasta; Radlanski, Ralf J; Tucker, Abigail S; Renz, Herbert; Míšek, Ivan; Matalová, Eva

    2011-01-01

    The first mouse molar (M1) is the most common model for odontogenesis, with research particularly focused on prenatal development. However, the functional dentition forms postnatally, when the histogenesis and morphogenesis of the tooth is completed, the roots form and the tooth physically anchors into the jaw. In this work, M1 was studied from birth to eruption, assessing morphogenesis, proliferation and apoptosis, and correlating these with remodeling of the surrounding bony tissue. The M1 completed crown formation between postnatal (P) days 0–2, and the development of the tooth root was initiated at P4. From P2 until P12, cell proliferation in the dental epithelium reduced and shifted downward to the apical region of the forming root. In contrast, proliferation was maintained or increased in the mesenchymal cells of the dental follicle. At later stages, before tooth eruption (P20), cell proliferation suddenly ceased. This withdrawal from the cell cycle correlated with tooth mineralization and mesenchymal differentiation. Apoptosis was observed during all stages of M1 postnatal morphogenesis, playing a role in the removal of cells such as osteoblasts in the mandibular region and working together with osteoclasts to remodel the bone around the developing tooth. At more advanced developmental stages, apoptotic cells and bodies accumulated in the cell layers above the tooth cusps, in the path of eruption. Three-dimensional reconstruction of the developing postnatal tooth and bone indicates that the alveolar crypts form by resorption underneath the primordia, whereas the ridges form by active bone growth between the teeth and roots to form a functional complex. PMID:21418206

  19. Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

    PubMed Central

    2017-01-01

    Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

  20. Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb.

    PubMed

    Liu, Annie; Urban, Nathaniel N

    2017-01-01

    Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB.

  1. Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats

    PubMed Central

    2016-01-01

    Prestin is the motor protein expressed in the cochlear outer hair cells (OHCs) of mammalian inner ear. The electromotility of OHCs driven by prestin is responsible for the cochlear amplification which is required for normal hearing in adult animals. Postnatal expression of prestin and activity of OHCs may contribute to the maturation of hearing in rodents. However, the temporal and spatial expression of prestin in cochlea during the development is not well characterized. In the present study, we examined the expression and function of prestin from the OHCs in apical, middle, and basal turns of the cochleae of postnatal rats. Prestin first appeared at postnatal day 6 (P6) for basal turn, P7 in middle turn, and P9 for apical turn of cochlea. The expression level increased progressively over the next few days and by P14 reached the mature level for all three segments. By comparison with the time course of the development of auditory brainstem response for different frequencies, our data reveal that prestin expression synchronized with the hearing development. The present study suggests that the onset time of hearing may require the expression of prestin and is determined by the mature function of OHCs. PMID:28097024

  2. Peripheral chemoreceptors: postnatal development and cytochemical findings in Sudden Infant Death Syndrome.

    PubMed

    Porzionato, Andrea; Macchi, Veronica; Parenti, Anna; Matturri, Luigi; De Caro, Raffaele

    2008-03-01

    The aim of the present study is to give a review of the postnatal development of peripheral chemoreceptors - carotid body, paraganglia, and pulmonary neuroendocrine cells (PNEC) - with implications in Sudden Infant Death Syndrome (SIDS). In the postnatal period, the hypoxic chemosensitivity of the carotid body gradually develops. Changes include proliferation of type I and II cells, increased numbers of dense core vesicles and K+ channels, and modifications of neurotransmitter/neuromodulator and receptor expression. Chromaffin paraganglia show increased expression of nitric oxide synthase and neuropeptides, and increased innervation. Innervation of PNEC develops fully only in the first postnatal period, after which their density falls. The neuropeptides produced by PNEC also changes, with increased expression of calcitonin gene-related peptide and neuropeptide YY and reduced expression of calcitonin and gastrin-releasing peptide. Most of the findings in the carotid body of SIDS victims, i.e., decrease in type I cells and dense cytoplasmic granules, and increase in progenitor cells, indicates immaturity of the carotid body, which may play a role in SIDS in the form of underlying biologic vulnerability. Aorticopulmonary paraganglia hyperplasia and increase of PNEC are also found in SIDS, and may be epiphenomena of alterations of the respiratory function with a pathogenetical role in SIDS. A comprehensive view of the pathogenesis of SIDS should also arise from the integration of peripheral chemoreceptors findings with neuro- and cardiopathologic ones.

  3. Underestimated contribution of skeletal muscle in ornithine metabolism during mouse postnatal development.

    PubMed

    Ladeuix, Benjamin; Duchamp, Claude; Levillain, Olivier

    2014-01-01

    Ornithine aminotransferase (L-ornithine 2-oxoacid aminotransferase, OAT) is widely expressed in organs, but studies in mice have focused primarily on the intestine, kidney and liver because of the high OAT-specific activity in these tissues. This study aimed to investigate OAT activity in adult mouse tissues to assess the potential contribution to ornithine metabolism and to determine OAT control during postnatal development. OAT activity was widely distributed in mouse tissues. Sexual dimorphism was observed for most tissues in adults, with greater activity in females than in males. The contribution of skeletal muscles to total OAT activity (34% in males and 27% in females) was the greatest (50%) of the investigated tissues in pre-weaned mice and was similar to that of the liver in adults. OAT activity was found to be regulated in a tissue-specific manner during postnatal development in parallel with large changes in the plasma testosterone and corticosterone levels. After weaning, OAT activity markedly increased in the liver but dropped in the skeletal muscle and adipose tissue. Anticipating weaning for 3 days led to an earlier reduction of OAT activity in skeletal muscles. Orchidectomy in adults decreased OAT activity in the liver but increased it in skeletal muscle and adipose tissue. We concluded that the contribution of skeletal muscle to mouse ornithine metabolism may have been underestimated. The regulation of OAT in skeletal muscles differs from that in the liver. The present findings suggest important and tissue-specific metabolic roles for OAT during postnatal development in mice.

  4. Histologic Features of Postnatal Development of Immune System Organs in the Sprague-Dawley Rat.

    PubMed

    Parker, George A; Picut, Catherine A; Swanson, Cynthia; Toot, Jonathan D

    2015-08-01

    The immune system of the rat undergoes substantial functional and morphological development during the postnatal period. Some aspects of this development are genetically predetermined, while other aspects depend on environmental influences. Detailed information on postnatal development is important in the interpretation of histopathologic findings in juvenile toxicology and pubertal assay studies, as well as other studies conducted in juvenile rats. Studies were conducted to provide detailed characterization of histologic features of the major functional compartments of immune system organs in male and female Sprague-Dawley rats at weekly intervals from the day of birth through postnatal day (PND) 42. Maturation of the individual immune system organs occurred across a range of ages, with histologic maturation of T-cell-related compartments typically occurring prior to maturation of B-cell-related compartments. The sequence of histologic maturation was bone marrow and thymus on PND 14, mesenteric lymph node on PND 21, Peyer's patches and bronchus-associated lymphoid tissue on PND 28, mandibular lymph node, nasopharynx-associated lymphoid tissue, and diffuse mucosal mononuclear cell population of small intestine on PND 35, and spleen on PND 42. An estimation of functional maturation can be made based on the morphological indications of maturity of each compartment of immune system organs, but histologic indications of maturity do not confirm functional immunocompetence.

  5. Early postnatal response of the spinal nucleus of the bulbocavernosus and target muscles to testosterone in male gerbils.

    PubMed

    Hadi Mansouri, S; Siegford, Janice M; Ulibarri, Catherine

    2003-05-14

    This study examined the response of the spinal nucleus of the bulbocavernosus (SNB) and the bulbocavernosus (BC) muscle, to testosterone in male Mongolian gerbils (Meriones unguiculatus) during the early postnatal period. Male gerbil pups were given testosterone propionate (TP) or vehicle for 2 days, then perfused on postnatal day (PND) 3, 5, 10 or 15. The BC and levator ani (LA) muscles were removed, weighed, and sectioned. Cross-sections of BC muscle fibers were measured and muscle fiber morphology examined. Spinal cords were removed and coronally sectioned in order to count and measure the SNB motoneurons. Following TP treatment, male pups of all ages had significantly heavier BC-LA muscles and larger fibers in the BC muscle compared to age-matched controls. The increase in muscle weight following TP treatment was greatest at PND10, while fiber size increased to a similar degree at all ages suggesting that hyperplasia as well as hypertrophy was responsible for the increase in muscle mass at this time. SNB motoneurons increased significantly in number and size with age and TP treatment. We hypothesize that the increase in SNB motoneuron number during normal ontogeny that can be augmented by TP treatment and represents an unusual means of establishing sexual dimorphism in the nervous system of a mammal through cell recruitment to the motor pool of a postnatal animal.

  6. Morphology of non-sensory epithelium during post-natal development of the rabbit vomeronasal organ.

    PubMed

    Elgayar, S A M; Eltony, S A; Othman, M A

    2014-08-01

    The vomeronasal organ (VNO), because of its ability to detect pheromones, has an important role in many social and sexual behaviours in mammals. It also mediates defensive behaviours through detection of protein pheromone homologues. A detailed morphological description of the post-natal development of the 'non-sensory' epithelium (NSE) of the female rabbit is recorded. Histological techniques were used to study the NSE of the VNO in post-natal development of female rabbits. The study focused on the following post-natal ages: newborn, 1 week, 2 weeks and 1 month (five animals each) beside to two adult animals. The rabbit VNO was surrounded externally by bony capsule and internally by cartilaginous capsule. NSE was pseudostratified columnar partially ciliated epithelium without goblet cells. In addition to basal cells, NSE contained ciliated and three types of non-ciliated columnar cells (dark, pale and light). At birth, dark cells may have primary cilia. By 1 month, the cytoplasm became lighter with less free ribosomes. The pale cells had electron-lucent cytoplasm, which contained a few organelles. Mitotic figures were observed in basal and columnar cells, particularly during the first 2 weeks of post-natal development. Light columnar cells were common during the first week. Numerous leucocytes and a few nerve endings were detected intra-epithelial. Scanning electron microscope revealed a gradual increase in height of microvilli of non-ciliated cells. Ciliated cells had cilia and microvilli. Cells were arranged singly, in clumps or in a dense population of cells. The rabbit VNO-NSE had a unique morphological structure.

  7. [The cyclic organization of sleep in early ontogenesis in different conditions of intrauterine fetus development].

    PubMed

    Evsiukova, I I

    2013-02-01

    The modern data about sleep development in early ontogenesis of newborns infants are presented. EEG-polysomnographic studies in newborns with different perinatal pathology document patterns of postnatal brain maturation have diagnostic and prognostic value.

  8. The importance of selenium in the prenatal and postnatal development of calves and lambs.

    PubMed

    Bostedt, H; Schramel, P

    1990-02-01

    Selenium deficiency is responsible for Zenker type muscle degeneration in calves, lambs, and foals in the prenatal and postnatal stages of development. Investigations have shown that the selenium GSH Px, and vitamin E content of the maternal and fetal parts of the placenta in cattle are different. Similarly, low concentrations of selenium are present in milk from cows and sheep. In addition to an inadequate supply of selenium and vitamin E as a contributory cause of fetal nutritive muscular dystrophy (FNMD), it is assumed that a placental transport block and/or impaired selenium metabolism in the placenta are also responsible. Postnatal nutritive muscular dystrophy, however, is attributed to either acute selenium and vitamin E deficiency in basic feed or impaired plant absorption of selenium as a result of antagonistic elements, such as sulphur.

  9. Expression of TLR2 and TLR4 in murine small intestine during postnatal development.

    PubMed

    Inoue, Ryo; Yajima, Takaji; Tsukahara, Takamitsu

    2017-02-01

    The important role played by the gut microbiota in host immunity is mediated, in part, through toll-like receptors (TLRs). We evaluated the postnatal changes in expression of TLR2 and TLR4 in the murine small intestine and assessed how expression is influenced by gut microbiota. The expression of TLR2 and TLR4 in the murine small intestine was highly dynamic during development. The changes were especially profound during the suckling period, with the maximal mRNA levels detected in the mid-suckling period. Immunohistochemical and flow-cytometric analyses indicated that the changes in TLR2 and TLR4 expression involve primarily epithelial cells. The germ-free mice showed minor changes in TLR2/TLR4 mRNA and TLR2 protein during the suckling period. This study demonstrated that the postnatal expression of TLR2 and TLR4 in small intestinal epithelial cells is dynamic and depends on the presence of commensal intestinal microbiota.

  10. Proteomic studies of rat tibialis anterior muscle during postnatal growth and development.

    PubMed

    Sun, Hualin; Zhu, Ting; Ding, Fei; Hu, Nan; Gu, Xiaosong

    2009-12-01

    In this study, a proteomic analysis consisting of two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry was accomplished to investigate the complex protein expression patterns in rat tibialis anterior muscle during postnatal 3-month period. We determined the time-dependent expression alterations of 107 protein spots, among which 53 protein spots were identified. These identified proteins included skeletal contractile proteins, metabolic enzymes, chaperone, intermediate filament, and signal transduction proteins. The time-dependent expression of three proteins, such as Mylpf, desmin, and RKIP, was confirmed by Western blot analysis and immunohistochemistry. The functional implication of these expression changes was also discussed. We further analyzed the linkage and interactions among the differentially expressed proteins (MAPK1, RKIP, AHSG, etc.). Collectively, the results might add to the understanding of the molecular mechanisms regulating postnatal growth and development of rat tibialis anterior muscle.

  11. The Impact of the in utero and Early Postnatal Environments on Grey and White Matter Volume: A Study with Adolescent Monozygotic Twins.

    PubMed

    Levesque, Melissa L; Fahim, Cherine; Ismaylova, Elmira; Verner, Marie-Pier; Casey, Kevin F; Vitaro, Frank; Brendgen, Mara; Dionne, Ginette; Boivin, Michel; Tremblay, Richard E; Booij, Linda

    2015-01-01

    Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development.

  12. Early postnatal diets affect the bioregional small intestine microbiome and ileal metabolome in neonatal piglets

    USDA-ARS?s Scientific Manuscript database

    Exclusive breastfeeding is known to be protective against gastrointestinal disorders and may modify gut development. Although the gut microbiome has been implicated, little is known about how early diet impacts the small intestinal microbiome, and how microbial shifts impact gut metabolic physiology...

  13. Postnatal development of layer III pyramidal cells in the primary visual, inferior temporal, and prefrontal cortices of the marmoset.

    PubMed

    Oga, Tomofumi; Aoi, Hirosato; Sasaki, Tetsuya; Fujita, Ichiro; Ichinohe, Noritaka

    2013-01-01

    Abnormalities in the processes of the generation and/or pruning of dendritic spines have been implicated in several mental disorders including autism and schizophrenia. We have chosen to examine the common marmoset (Callithrix jacchus) as a primate model to explore the processes. As a first step, we studied the postnatal development of basal dendritic trees and spines of layer-III pyramidal cells in the primary visual sensory cortex (V1), a visual association cortex (inferior temporal area, TE), and a prefrontal cortex (area 12, PFC). Basal dendrites in all three areas were longer in adulthood compared with those in the newborn. In particular, rapid dendritic growth occurred in both TE and PFC around the second postnatal month. This early growth spurt resulted in much larger dendritic arbors in TE and PFC than in V1. The density of the spines along the dendrites peaked at 3 months of age and declined afterwards in all three areas: the degree of spine pruning being greater in V1 than in TE and PFC. The estimates of the total numbers of spines in the basal dendrites of a single pyramidal cell were larger in TE and PFC than in V1 throughout development and peaked around 3 months after birth in all three areas. These developmental profiles of spines and dendrites will help in determining assay points for the screening of molecules involved in spinogenesis and pruning in the marmoset cortex.

  14. Melatonin secretion during postnatal development in wild and domestic female lambs.

    PubMed

    Gómez-Brunet, A; Santiago-Moreno, J; Chemineau, P; Malpaux, B; López-Sebastián, A

    2010-05-01

    This study examines the patterns of melatonin secretion during postnatal development in wild (mouflon; n = 7) and domestic (Spanish Merino; n = 6) female lambs under their natural photoperiod conditions. The aim was to determine whether these types of sheep which differ in the timing of puberty, also differ in the establishment of daily melatonin secretory rhythms and/or in the nocturnal plasma melatonin secretion. In addition, the time when the lambs first reached nocturnal levels of melatonin similar to adults was also evaluated. For this purpose, the melatonin secretion in lambs was compared with those of their mothers. A day/night (D/N) difference in plasma melatonin concentration was noticed as early as 1 day after birth in the Merino female lambs (D: 5.9 +/- 1.0 pg/ml compared to N: 22.0 +/- 3.3 pg/ml; p < 0.05), and by 1 week after birth in the mouflon female lambs (D: 4.9 +/- 0.3 pg/ml compared to N: 56.9 +/- 15.3 pg/ml; p < 0.05). An effect of the genotype (p < 0.05) and age (p < 0.01) was detected on mean nocturnal plasma melatonin concentrations, which were lower in the Merino than in the mouflon lambs. Night-time plasma concentration of melatonin was also high in mouflon than in Merino mothers (p < 0.05). No differences were detected between the wild genotype and the domestic one in the time when the lambs first reached nocturnal levels of melatonin similar to those of their mothers.

  15. Postnatal development of neuronal responses to frequency-modulated tones in chinchilla auditory cortex.

    PubMed

    Brown, Trecia A; Harrison, Robert V

    2010-01-14

    Responses to cortical neurons to frequency-modulated (FM) stimuli have been described in various adult animal models. Here, we ask whether FM coding at the cortical level is innate or if it is influenced by postnatal environmental experience. We report on the FM response properties of neurons in core auditory cortex of newborn (P3), 1-month-old (P28) and adult (>1-year-old) anesthetized chinchillas (Chinchilla laniger). Upward and downward linear FM sweeps spanning frequencies from 0.1 to 20 kHz were presented monaurally at speeds of 0.05 to 0.82 kHz/ms. Results indicated that neurons in neonatal pups were responsive to FM stimulation. While we observed a developmental increase in the selectivity of units for FM sweep direction (p<0.01, one-way ANOVA), selectivity for sweep speed appeared to be established early in development. Chinchilla pup neurons also demonstrated single-peak (single dominant response during FM sweep presentation) and multi-peak (multiple distinct responses during FM sweep) temporal response patterns to FM stimuli similar to those observed in adults. A developmental increase in the proportion of multi-peak units closely paralleled a previously reported increase in the complexity of pure tone receptive fields. We suggest that units in core auditory cortex of the chinchilla are not uniquely activated by FM sounds but that FM responses are largely predictable based on how changing frequency stimuli interact with the tonal receptive fields of neurons in the auditory cortex.

  16. Study of fetal and postnatal morphological development of the brain sulci.

    PubMed

    Nishikuni, Koshiro; Ribas, Guilherme Carvalhal

    2013-01-01

    The surface of the developing fetal brain undergoes significant morphological changes during fetal growth. The purpose of this study was to evaluate the morphological development of the brain sulci from the fetal to the early postnatal period. Two hundred fourteen brain hemispheres from 107 human brain specimens were examined to evaluate the timing of sulcal formation, from its appearance to its complete development. These brains were obtained from cadavers ranging in age from 12 weeks of gestation to 8 months of postnatal life. The order of appearance of the cerebral sulci, and the number and percentages of specimens found in this study were as follows: longitudinal cerebral fissure at 12 weeks (10/10, 100%); callosal sulcus at 12 weeks (10/10, 100%); hippocampal sulcus at 15 weeks (7/10, 70%); lateral sulcus at 17 weeks (20/22, 90.9%); circular insular sulcus at 17 weeks (18/22, 81.8%); olfactory sulcus at 17 weeks (18/22, 81.8%); calcarine sulcus at 17 weeks (14/22, 63.6%); parietooccipital sulcus at 17 weeks (11/22, 50%); cingulate sulcus at 19 weeks (16/20, 80%); central sulcus at 21 weeks (22/38, 57.9%); orbital sulcus at 22 weeks (9/16, 56.2%); lunate sulcus at 24 ± 2 weeks (12/16, 75%); collateral sulcus at 24 ± 2 weeks (8/16, 50%); superior frontal sulcus at 25 ± 2 weeks (5/6, 83.3%); rhinal sulcus at 25 ± 2 weeks (3/6, 50%); precentral sulcus at 26 ± 3 weeks (2/4, 50%); postcentral sulcus at 26 ± 3 weeks (2/4, 50%); superior temporal sulcus at 26 ± 3 weeks (2/4, 50%); central insular sulcus at 29 ± 2 weeks (4/4, 100%); intraparietal sulcus at 29 ± 2 weeks (2/4, 50%); paraolfactory sulcus at 29 ± 2 weeks (2/4, 50%); inferior frontal sulcus at 30 ± 3 weeks (2/4, 50%); transverse occipital sulcus at 30 ± 3 weeks (2/4, 50%); occipitotemporal sulcus at 30 ± 3 weeks (2/4, 50%); marginal branch of the cingulate sulcus at 30 ± 3 weeks (2/4, 50%); paracentral sulcus at 30 ± 3 weeks (2/4, 50%); subparietal sulcus at 30 ± 3 weeks (2/4, 50%); inferior

  17. The postnatal development of the alimentary canal in the opossum. II. Stomach.

    PubMed Central

    Krause, W J; Cutts, J H; Leeson, C R

    1976-01-01

    The postnatal development of the gastric mucosa in the opossum has been traced with the light, transmission and scanning electron microscopes. The formation of fovea and gastric glands occurs simultaneously during the postnatal period. During the first 60 postnatal days the developing gastric glands are composed of undifferentiated cells, parietal cells and scattered endocrine cells. Chief cells are not present until just before weaning (13 cm, i.e. ca. 75 days). Juvenile and adult animals show only a small population of chief cells, and these are confined to the bases of the gastric glands. The pH of stomach contents ranges from 6-0 to 6-5 until the time of appearance of solid food within the stomach, when it drops to 2-0-2-5. The surface cells lining the gastric lumen contain a considerable amount of what appears to be lipid during the first 3 weeks after birth, and this may indicate that the gastric mucosa is involved in the absorption of lipid during this period. The mode of lipid absorption appears to be different from that described for the intestinal tract of several other species. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 21 Fig. 22 Fig. 23 Fig. 24 Fig. 25 Fig. 26 Fig. 27 Fig. 28 PMID:1034628

  18. The expression and localization of inhibin isotypes in mouse testis during postnatal development

    PubMed Central

    Kim, Yujin; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Kim, Jong Choon; Bae, Chun-Sik; Kim, Seungjoon; Shin, Taekyun; Kim, Sung-Ho

    2008-01-01

    Inhibin, which is important for normal gonadal function, acts on the pituitary gonadotropins to suppress follicle-stimulating hormone (FSH) secretion. The level and cellular localization of the inhibin isotypes, α, βA and βB, in the testis of mice were examined during postnatal development in order to determine if inhibin expression is related to testicular maturation. Mouse testes were sampled on postnatal days (PNDs) 1, 3, 6, 18, 48 and 120, and analyzed by Western blotting and immunofluorescence. Western blot analysis showed very low levels of inhibin α, βA and βB expression in the testes at days 1 to 6 after birth. The levels then increased gradually from PND 18 to 48-120, and there were significant peaks at PND 48. Inhibin α, βA and βB were detected in testicular cells during postnatal development using immunohistochemistry. The immunoreactivity of inhibin α was rarely observed in testicular cells during PND 1 to 6, or in the cytoplasmic process of Sertoli cells surrounding the germ cells and interstitial cells during PND 18 to 120. Inhibin βA and βB immunoreactivity was rarely observed in the testis from PND 1 to 6. On the other hand, it was observed in some spermatogonial cells, as well as in the interstitial space between PND 48 and PND 120. We conclude that the expression of inhibin isotypes increases progressively in the testis of mice with increasing postnatal age, suggesting that inhibin is associated with a negative feedback signal for FSH in testicular maturation. PMID:19043308

  19. Effects of 0. 6-Gy prenatal X irradiation on postnatal neurophysiologic development in the Wistar rat

    SciTech Connect

    Jensh, R.P.; Brent, R.L.

    1986-04-01

    Forty-one pregnant Wistar strain rats were irradiated with 0.6-Gy X rays or were sham irradiated on the 9th or 17th days of gestation to determine if this dosage level would result in alterations in postnatal neurophysiologic development. Half of the mothers were sacrificed at term, and the developmental status of 221 newborns was evaluated. The remaining mothers delivered and raised their litters. The 161 offspring were observed for the age of attainment of the following physiologic parameters: pinna detachment, eye opening, testes opening. Offspring were also tested for the acquisition of the following selected reflexes: surface righting, negative geotaxis, auditory startle, air righting, and visual placing. Term fetal weight was lower than the controls in the group irradiated on the 9th day but was recuperable postnatally. None of the 9 developmental tests performed postnatally were abnormal in the animals irradiated on the 9th day. Thus, at least with regard to these measures, the surviving embryos exposed during the all-or-none period could not be differentiated from the controls. Offspring irradiated on the 17th day exhibited retarded growth which persisted during neonatal life. The three-day-mean neonatal weight was significantly lower in the group irradiated on the 17th day compared to controls. There were no significant maternal body weight or organ/weight differences between the groups. Rats exposed in utero on the 17th day had a significantly delayed acquisition of air righting. These results demonstrate that 0.6-Gy in utero irradiation on the 17th day of gestation can cause subtle alterations in growth and development of the Wistar strain rat during postnatal life.

  20. Postnatal Exposure to Methyl Mercury from Fish Consumption: a Review and New Data from the Seychelles Child Development Study

    PubMed Central

    Myers, Gary J.; Thurston, Sally W.; Pearson, Alexander T.; Davidson, Philip W.; Cox, Christopher; Shamlaye, Conrad F.; Cernichiari, Elsa; Clarkson, Thomas W.

    2009-01-01

    Background Fish is an important source of nutrition worldwide. Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain development after birth and thus adversely affect children’s developmental outcomes. We reviewed postnatal MeHg exposure and the associations that have been published to determine the issues associated with it and then carried out a series of analyses involving alternative metrics of postnatal MeHg exposure in the Seychelles Child Development Study (SCDS) Main Cohort. Methods The SCDS is a prospective longitudinal evaluation of prenatal MeHg exposure from fish consumption. The Main Cohort includes 779 subjects on whom recent postnatal exposure data were collected at the 6, 19, 29, 66, and 107 month evaluations. We examined the association of recent postnatal MeHg exposure with multiple 66 and 107-month outcomes and then used three types of alternative postnatal exposure metrics to examine their association with the children’s intelligence quotient (IQ) at 107 months of age. Results Recent postnatal exposure at 107 months of age was adversely associated with four endpoints, three in females only. One alternative postnatal metric was beneficially associated with 9-year IQ in males only. Conclusions We found several associations between postnatal MeHg biomarkers and children’s developmental endpoints. However, as has been the case with prenatal MeHg exposure in the SCDS Main Cohort study, no consistent pattern of associations emerged to support a causal relationship. PMID:19442817

  1. Early Postnatal Exposure to Cigarette Smoke Leads to Later Airway Inflammation in Asthmatic Mice

    PubMed Central

    Huang, Fei; Cheng, Hang; Zhang, Yu-tong; Ju, Yang-hua; Li, Ya-nan

    2017-01-01

    Background and objective Asthma is one of the most common airway inflammatory diseases. In most cases, asthma development is related to ubiquitous harmful environmental exposure factors in early-life. Previous studies have indicated that smoking can promote asthma development and increase the difficulty of asthma control. The aim of this study was to determine the effects of early-life CS exposure on ovalbumin (OVA)-sensitized asthmatic mice. Methods Pathological and immunological functions were analyzed in an adult asthma mice model in which mice were sensitized with OVA combined with early-life CS exposure. Results Mice exposed to CS for only 5 weeks demonstrated significantly reduced pulmonary compliance, increased airway inflammation, and augmented cellular and humoral immune responses. In addition, CS inhalation was sufficient to facilitate OVA sensitization and challenge asthmatic development. Meanwhile, CS exposure amplified regulatory T cell-mediated immunity inhibition, but still did not offset the increased effector T cell-mediated inflammatory response. Conclusion Early-life CS exposure is significantly associated with later pulmonary injury and aggravation of T-cell immunologic derangement in asthmatic mice. PMID:28135326

  2. Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.

    PubMed

    Trofimov, S S; Voronina, T A; Guzevatykh, L S

    2005-06-01

    We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity.

  3. Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties.

    PubMed

    McMurray, Matthew S; Oguz, Ipek; Rumple, Ashley M; Paniagua, Beatriz; Styner, Martin A; Johns, Josephine M

    2015-01-01

    Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance, data must be carefully collected using translational methods. The goal of this study was two-fold: (1) to determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging, and (2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1-20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus pallidus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures but does not

  4. Early Program Development

    NASA Image and Video Library

    2004-04-15

    During the Space Shuttle development phase, Marshall plarners concluded a Heavy Lift Launch Vehicle (HLLV) would be needed for successful Space Industrialization. Shown here in this 1976's artist's conception is an early version of the HLLV during launch.

  5. Postnatal development of a segmental switch enables corticospinal tract transmission to spinal forelimb motor circuits.

    PubMed

    Chakrabarty, Samit; Martin, John H

    2010-02-10

    Development of skilled movements and the corticospinal tract (CST) begin prenatally and continue postnatally. Because the CST is required for skilled movements in maturity, it is accepted that motor skills cannot occur until the CST develops a mature organization. We recently showed that the CST plays an essential role in postnatal development of interneurons comprising the spinal circuits it engages. We proposed that CST signals are more effectively transmitted to ventral motor circuits after interneuron maturation, thereby enabling expression of CST motor functions, suggesting development of a segmental switch promoting transmission. We tested this by recording CST-evoked focal synaptic potentials, extracellularly, in the cervical enlargement of cats before and after interneuron maturation [postnatal week 5 (PW5) to PW7]. We compared monosynaptic CST amplitude input to segmental circuits with oligosynaptic ventral horn responses, as a measure of CST-evoked segmental response transmission from input to output. The M1 primary motor cortex was unilaterally inactivated between PW5 and PW7 to determine activity dependence. CST interneuron contacts were identified using confocal microscopy. CST terminals contact diverse interneuron classes. CST stimulation strongly activated ventral motor circuits at the ages when both interneurons and CST spinal terminations have developed a mature phenotype, supporting development of segmental transmission of CST signals. CST activity blockade impeded development of effective segmental transmission by the inactivated CST and created a novel path for transmission from the ipsilateral, unaffected, CST. Our findings show that development of segmental CST signal transmission regulates nascent CST motor control functions and provide insight into systems-level mechanisms for protracted motor skill development.

  6. Chronic overexpression of cerebral Epo improves the ventilatory response to acute hypoxia during the postnatal development.

    PubMed

    Caravagna, Céline; Gasser, Edith M Schneider; Ballot, Orlane; Joseph, Vincent; Soliz, Jorge

    2015-08-01

    Clinicians observed that the treatment of premature human newborns for anemia with erythropoietin (Epo) also improved their respiratory autonomy. This observation is in line with our previous in vitro studies showing that acute and chronic Epo stimulation enhances fictive breathing of brainstem-spinal cord preparations of postnatal day 3-4 mice during hypoxia. Furthermore, we recently reported that the antagonization of the cerebral Epo (by using the soluble Epo receptor; sEpoR) significantly reduced the basal ventilation and the hypoxic ventilatory response of 10 days old mice. In this study, we used transgenic (Tg21) mice to investigate the effect of the chronic cerebral Epo overexpression on the modulation of the normoxic and hypoxic ventilatory drive during the post-natal development. Ventilation was evaluated by whole body plethysmography at postnatal ages 3 (P3), 7 (P7), 15 (P15) and 21 (P21). In addition Epo quantification was performed by RIA and mRNA EpoR was evaluated by qRT-PCR. Our results showed that compared to control animals the chronic Epo overexpression stimulates the hypoxic (but not the normoxic) ventilation assessed as VE/VO2 at the ages of P3 and P21. More interestingly, we observed that at P7 and P15 the chronic Epo stimulation of ventilation was attenuated by the down regulation of the Epo receptor in brainstem areas. We conclude that Epo, by stimulating ventilation in brainstem areas crucially helps tolerating physiological (e.g., high altitude) and/or pathological (e.g., respiratory disorders, prematurity, etc.) oxygen deprivation at postnatal ages.

  7. Influence of intrauterine growth restriction on airway development in fetal and postnatal sheep.

    PubMed

    Wignarajah, Dharshini; Cock, Megan L; Pinkerton, Kent E; Harding, Richard

    2002-06-01

    Epidemiologic studies suggest that intrauterine growth restriction (IUGR) can lead to impaired lung function, yet little information exists on the effects of IUGR on airway development. Our objectives were to characterize morphometrically effects of IUGR on airway structure in the fetus and to determine whether alterations persist into postnatal life. We used two groups of sheep, each with appropriate controls; a fetal group was subjected to IUGR by restriction of placental function from 120 to 140 d (term approximately 147 d), and a postnatal group, killed 8 wk after birth, was subjected to IUGR from 120 d to birth at term. In both fetuses and postnatal lambs, IUGR did not alter lung weight relative to body weight. In IUGR fetuses, the luminal areas and basement membrane perimeters of the trachea and larger bronchi (generations 0-8, trachea = 0) were smaller than in controls. Airway wall areas, relative to basement membrane perimeters, were reduced in IUGR fetuses compared with controls, largely due to reduced areas of cartilage and epithelium. At 8 wk after birth, there were no significant differences in airway dimensions between IUGR and control lambs. However, the number of profiles of bronchial submucosal glands, relative to basement membrane perimeters, was lower in IUGR lambs than in controls and the area of epithelial mucin was increased. We conclude that restriction of fetal growth during late gestation impairs the growth of bronchial walls that could affect airway compliance in the immediate postnatal period. Although airway growth deficits are reversed by 8 wk, alterations in mucus elements persist.

  8. [Parenteral nutrition in premature infants: practical aspects to optimize postnatal growth and development].

    PubMed

    Senterre, T; Rigo, J

    2013-09-01

    Nutrition and growth are still a major challenge in neonatal intensive care. Many studies have demonstrated that premature infants frequently develop severe cumulative nutritional deficit during the first weeks of life. This malnutrition is the primary etiology of postnatal growth restriction, which is still universally described in very premature infants. Furthermore, both postnatal nutritional deficit and postnatal growth restriction have been associated with adverse long-term outcome in adulthood. Due to their immaturity, premature infants are frequently not fed by the enteral route. Therefore, parenteral nutrition remains an essential therapy in neonatology. Most recent recommendations suggest starting parenteral nutrition as soon as possible after birth with a minimum of 40 kcal/kg/day with around 2-3g/kg/day of amino acids and 1g/kg/day of lipids. Afterwards, intake should increase rapidly during the first week of life, up to 90-120 kcal/kg/day with around 3.5 g/kg/day amino acids and 3g/kg/day of lipids. There is great heterogeneity in parenteral nutrition practices among neonatal units, with frequent discrepancies. This article discusses the principal theoretical aspects of parenteral nutrition in premature infants, the guidelines, and the opportunity to optimize nutritional support routinely, especially in very premature infants. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Postnatal development of retrosplenial projections to the parahippocampal region of the rat

    PubMed Central

    Sugar, Jørgen; Witter, Menno P

    2016-01-01

    The rat parahippocampal region (PHR) and retrosplenial cortex (RSC) are cortical areas important for spatial cognition. In PHR, head-direction cells are present before eye-opening, earliest detected in postnatal day (P)11 animals. Border cells have been recorded around eye-opening (P16), while grid cells do not obtain adult-like features until the fourth postnatal week. In view of these developmental time-lines, we aimed to explore when afferents originating in RSC arrive in PHR. To this end, we injected rats aged P0-P28 with anterograde tracers into RSC. First, we characterized the organization of RSC-PHR projections in postnatal rats and compared these results with data obtained in the adult. Second, we described the morphological development of axonal plexus in PHR. We conclude that the first arriving RSC-axons in PHR, present from P1 onwards, already show a topographical organization similar to that seen in adults, although the labeled plexus does not obtain adult-like densities until P12. DOI: http://dx.doi.org/10.7554/eLife.13925.001 PMID:27008178

  10. Development and psychometric testing of the Chinese Postnatal Risk Factors Questionnaire (CPRFQ) for postpartum depression.

    PubMed

    Yan, Xiaoyu; Lu, Jun; Shi, Shenxun; Wang, Ximei; Zhao, Rui; Yan, Yuan; Chen, Gang

    2015-04-01

    This article describes the development and psychometric assessment of the Chinese Postnatal Risk Factors Questionnaire (CPRFQ). There were four phases in this process: (1) the items were generated using a literature review and a focus group, (2) content validity was evaluated by an expert panel, (3) a pilot study was conducted with 45 postpartum women to refine the scale, and (4) a convenience sample of 256 postpartum women in China was recruited to complete the questionnaire. Construct validity was established by exploratory factor analysis; a four-factor structure of the scale was accepted (social and family, personality and relationship, mother and infant, maternal feelings and 'doing the month'). These factors explained 47.46 % of the variance. Pearson's correlation coefficient was conducted to test convergent validity with the Edinburgh Postnatal Depression Scale (EPDS) (r = 0.54; p < 0.001). The Cronbach's alpha coefficient of the four subscales ranged from 0.58 to 0.71. The final 18-item version of the questionnaire is potentially a valuable tool for assessing postnatal risk factors in Chinese postpartum mothers.

  11. The effect of low-to-moderate-dose ethanol consumption on rat mammary gland structure and function and early postnatal growth of offspring.

    PubMed

    Probyn, Megan E; Lock, Emma-Kate; Anderson, Stephen T; Walton, Sarah; Bertram, John F; Wlodek, Mary E; Moritz, Karen M

    2013-05-15

    High levels of alcohol consumption during pregnancy can lead to growth deficits in early postnatal life. However, the effects of low-to-moderate alcohol consumption during pregnancy are less clearly defined. The aim of this study was to determine whether low-to-moderate ethanol (EtOH) consumption throughout pregnancy in the rat alters maternal mammary gland morphology and milk protein levels, thereby affecting lactation and the growth of pups after birth. Sprague-Dawley rats were fed an ad libitum liquid diet ± 6% vol/vol EtOH throughout pregnancy. Mammary glands from dams were collected at embryonic day (E) 20 or postnatal day (PN) 1, and expression of milk proteins (α-lactalbumin, β-casein, and whey acidic protein) was examined. In addition, relative amounts of alveoli, lactiferous ducts, adipose tissue, and blood vessels were determined at PN1. A subset of rats gave birth, and offspring growth and milk intake were recorded. Mammary gland weight was unaltered by EtOH, and stereological analysis showed no differences in gland structure compared with control. Although there were no significant changes in mammary gland gene expression at the RNA level, protein levels of α-lactalbumin were increased and whey acidic protein were decreased by EtOH. Offspring of EtOH-fed dams consumed less milk than controls in the lactational period; however, this did not alter their early postnatal growth. Overall, it appears that low-to-moderate-dose prenatal EtOH exposure does not significantly alter mammary gland development but may alter the composition of the various proteins found within the milk in a manner that maintains overall pup growth.

  12. Post-natal development of type 1 cannabinoid receptor immunoreactivity in the rat hippocampus.

    PubMed

    Morozov, Yury M; Freund, Tamás F

    2003-09-01

    Type 1 cannabinoid receptors, selectively located on axon terminals of GABAergic interneurons in the hippocampus, are known to be involved in endocannabinoid-mediated retrograde synaptic signalling. The question arises whether type 1 cannabinoid receptors appear on these axons during early post-natal life, when GABAergic transmission is still depolarizing, and whether there are any developmental changes in the cellular or subcellular expression pattern. Here we demonstrate, using single and double immunocytochemical methods at the light and electron microscopic levels, that type 1 cannabinoid receptors are expressed only on the membrane of axon terminals and pre-terminal axons but not on the soma-dendritic membrane at all examined timepoints between post-natal days 0 and 20, similar to the adult distribution. All type 1 cannabinoid receptor-positive boutons formed symmetric synapses. Granular labelling in the somata was already strong at post-natal day 0 and corresponded to multivesicular bodies, lysosomes, Golgi apparatus and rough endoplasmic reticulum. The type 1 cannabinoid receptor-positive axons were shown to originate largely from cholecystokinin-immunoreactive basket and bistratified neurons throughout the hippocampus (90% of all type 1 cannabinoid receptor-containing cells) and dentate gyrus (70% of all type 1 cannabinoid receptor-containing cells). The remaining cells have not been identified but probably belong to the somatostatin- and/or neuropeptide Y-containing subsets, as cholecystokinin-negative, type 1 cannabinoid receptor-positive axons have been observed in strata moleculare and lacunosum-moleculare of the dentate gyrus and CA1-3, respectively, where these neurons are known to arborize. No cell types were found that expressed type 1 cannabinoid receptors transiently at some developmental stage. We conclude that the cellular and subcellular pattern of type 1 cannabinoid receptor expression during early post-natal life is similar to the adult

  13. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep

    PubMed Central

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID:27257993

  14. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep.

    PubMed

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights.

  15. Risk of Learning and Behavioral Disorders Following Prenatal and Early Postnatal Exposure to Tetrachloroethylene (PCE)-contaminated Drinking Water

    PubMed Central

    Janulewicz, Patricia A; White, Roberta F; Winter, Michael R; Weinberg, Janice M; Gallagher, Lisa E; Vieira, Veronica; Webster, Thomas F; Aschengrau, Ann

    2008-01-01

    This population-based retrospective cohort study examined the association between developmental disorders of learning, attention and behavior and prenatal and early postnatal drinking water exposure to tetrachloroethylene (PCE) on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Mothers completed a questionnaire on disorders of attention, learning and behavior in their children and on potential confounding variables. The final cohort consisted of 2,086 children. Results of crude and multivariate analyses showed no association between prenatal exposure and receiving tutoring for reading or math, being placed on an Individual Education Plan, or repeating a school grade (adjusted Odds Ratios (OR)=1.0–1.2). There was also no consistent pattern of increased risk for receiving a diagnosis of Attention Deficit Disorder (ADD) or Hyperactive Disorder (HD), special class placement for academic or behavioral problems, or lower educational attainment. Modest associations were observed for the latter outcomes only in the low exposure group (e.g., adjusted ORs for ADD were 1.4 and 1.0 for low and high exposure, respectively). (All ORs are based on an unexposed referent group.) Results for postnatal exposure through age five years were similar to those for prenatal exposure. We conclude that prenatal and early postnatal PCE exposure is not associated with disorders of attention, learning and behavior identified on the basis of questionnaire responses and at the exposure levels experienced by this population. PMID:18353612

  16. Early postnatal stress alters extracellular signal-regulated kinase signaling in the corticolimbic system modulating emotional circuitry in adult rats.

    PubMed

    Ishikawa, Shuhei; Saito, Yasuhiro; Yanagawa, Yoshiki; Otani, Satoru; Hiraide, Sachiko; Shimamura, Kei-ichi; Matsumoto, Machiko; Togashi, Hiroko

    2012-01-01

    The present study elucidated whether early life stress alters the extracellular signal-regulated kinase (ERK) pathway that underlies fear retrieval and fear extinction based on a contextual fear conditioning paradigm, using a juvenile stress model. Levels of phospho-ERK (pERK), the active form of ERK, increased after fear retrieval in the hippocampal CA1 region but not in the medial prefrontal cortex (mPFC). ERK activation in the CA1 following fear retrieval was not observed in adult rats who received aversive footshock (FS) stimuli during the second postnatal period (2wFS), which exhibited low levels of freezing. In fear extinction, pERK levels in the CA1 were increased by repeated extinction trials, but they were not altered after extinction retrieval. In contrast, pERK levels in the mPFC did not change during extinction training, but were enhanced after extinction retrieval. These findings were compatible in part with electrophysiological data showing that synaptic transmission in the CA1 field and mPFC was enhanced during extinction training and extinction retrieval, respectively. ERK activation in the CA1 and mPFC associated with extinction processes did not occur in rats that received FS stimuli during the third postnatal period (3wFS), which exhibited sustained freezing behavior. The repressed ERK signaling and extinction deficit observed in the 3wFS group were ameliorated by treatment with the partial N-methyl-D-aspartate receptor agonist D-cycloserine. These findings suggest that early postnatal stress induced the downregulation of ERK signaling in distinct brain regions through region-specific regulation, which may lead to increased behavioral abnormalities or emotional vulnerabilities in adulthood.

  17. Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease.

    PubMed

    Lewis, Brandon W; Sultana, Razia; Sharma, Rahul; Noël, Alexandra; Langohr, Ingeborg; Patial, Sonika; Penn, Arthur L; Saini, Yogesh

    2017-08-01

    Secondhand smoke (SHS) exposure has been linked to the worsening of ongoing lung diseases. However, whether SHS exposure affects the manifestation and natural history of imminent pediatric muco-obstructive airway diseases such as cystic fibrosis remains unclear. To address these questions, we exposed Scnn1b transgenic (Scnn1b-Tg(+)) mice to SHS from postnatal day (PND) 3-21 and lung phenotypes were examined at PND22. Although a majority of filtered air (FA)-exposed Scnn1b-Tg(+) (FA-Tg(+)) mice successfully cleared spontaneous bacterial infections by PND22, the SHS-exposed Scnn1b-Tg(+) (SHS-Tg(+)) mice failed to resolve these infections. This defect was associated with suppressed antibacterial defenses, i.e., phagocyte recruitment, IgA secretion, and Muc5b expression. Whereas the FA-Tg(+) mice exhibited marked mucus obstruction and Th2 responses, SHS-Tg(+) mice displayed a dramatic suppression of these responses. Mechanistically, downregulated expression of IL-33, a stimulator of type II innate lymphoid cells, in lung epithelial cells was associated with suppression of neutrophil recruitment, IgA secretions, Th2 responses, and delayed bacterial clearance in SHS-Tg(+) mice. Cessation of SHS exposure for 21 d restored previously suppressed responses, including phagocyte recruitment, IgA secretion, and mucous cell metaplasia. However, in contrast with FA-Tg(+) mice, the SHS-Tg(+) mice had pronounced epithelial necrosis, alveolar space consolidation, and lymphoid hyperplasia; indicating lagged unfavorable effects of early postnatal SHS exposure in later life. Collectively, our data show that early postnatal SHS exposure reversibly suppresses IL-33 levels in airspaces which, in turn, results in reduced neutrophil recruitment and diminished Th2 response. Our data indicate that household smoking may predispose neonates with muco-obstructive lung disease to bacterial exacerbations. Copyright © 2017 by The American Association of Immunologists, Inc.

  18. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice.

    PubMed

    Yanai, Shogo; Hirano, Tetsushi; Omotehara, Takuya; Takada, Tadashi; Yoneda, Naoki; Kubota, Naoto; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2017-07-07

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

  19. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice

    PubMed Central

    YANAI, Shogo; HIRANO, Tetsushi; OMOTEHARA, Takuya; TAKADA, Tadashi; YONEDA, Naoki; KUBOTA, Naoto; YAMAMOTO, Anzu; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

    2017-01-01

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life. PMID:28579575

  20. A systematic approach towards the development of quality indicators for postnatal care after discharge in Flanders, Belgium.

    PubMed

    Helsloot, Kaat; Walraevens, Mieke; Besauw, Saskia Van; Van Parys, An-Sofie; Devos, Hanne; Holsbeeck, Ann Van; Roelens, Kristien

    2017-05-01

    to develop a set of quality indicators for postnatal care after discharge from the hospital, using a systematic approach. key elements of qualitative postnatal care were defined by performing a systematic review and the literature was searched for potential indicators (step 1). The potential indicators were evaluated by five criteria (validity, reliability, sensitivity, feasibility and acceptability) and by making use of the 'Appraisal of Guidelines for Research and Evaluation', the AIRE-instrument (step 2). In a modified Delphi-survey, the quality indicators were presented to a panel of experts in the field of postnatal care using an online tool (step 3). The final results led to a Flemish model of postnatal care (step 4). Flanders, Belgium PARTICIPANTS: health care professionals, representatives of health care organisations and policy makers with expertise in the field of postnatal care. after analysis 57 research articles, 10 reviews, one book and eight other documents resulted in 150 potential quality indicators in seven critical care domains. Quality assessment of the indicators resulted in 58 concept quality indicators which were presented to an expert-panel of health care professionals. After two Delphi-rounds, 30 quality indicators (six structure, 17 process, and seven outcome indicators) were found appropriate to monitor and improve the quality of postnatal care after discharge from the hospital. KEY CONCLUSIONS AND IMPLICATIONS FOR CLINICAL PRACTICE: the quality indicators resulted in a Flemish model of qualitative postnatal care that was implemented by health authorities as a minimum standard in the context of shortened length of stay. Postnatal care should be adjusted to a flexible length of stay and start in pregnancy with an individualised care plan that follows mother and new-born throughout pregnancy, childbirth and postnatal period. Criteria for discharge and local protocols about the organisation and content of care are essential to facilitate