bcl-x is expressed in embryonic and postnatal neural tissues and functions to prevent neuronal cell death.

Previous studies have implicated the bcl-2 protooncogene as a potential regulator of neuronal survival. However, mice lacking functional bcl-2 exhibited normal development and maintenance of the central nervous system (CNS). Since bcl-2 appears dispensable for neuronal survival, we have examined the expression and function of bcl-x, another member of the bcl-2 family of death regulatory genes. Bcl-2 is expressed in neuronal tissues during embryonic development but is down-regulated in the adult CNS. In contrast, Bcl-xL expression is retained in neurons of the adult CNS. Two different forms of bcl-x mRNA and their corresponding products, Bcl-xL and Bcl-x beta, were expressed in embryonic and adult neurons of the CNS. Microinjection of bcl-xL and bcl-x beta cDNAs into primary sympathetic neurons inhibited their death induced by nerve growth factor withdrawal. Thus, Bcl-x proteins appear to play an important role in the regulation of neuronal survival in the adult CNS.

Clathrin isoform CHC22, a component of neuromuscular and myotendinous junctions, binds sorting nexin 5 and has increased expression during myogenesis and muscle regeneration

The muscle isoform. of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear to be distinct from those of well-characterized clathrin-coated vesicles. In mature muscle CHC22 is preferentially concentrated at neuromuscular and myotendinous junctions, suggesting a role at sarcolemmal contacts with extracellular matrix. During myoblast differentiation, CHC22 expression is increased, initially localized with desmin and nestin and then preferentially segregated to the poles of fused myoblasts. CHC22 expression is also increased in regenerating muscle fibers with the same time course as embryonic myosin, indicating a role in muscle repair. CHC22 binds to sorting nexin 5 through a coiled-coil domain present in both partners, which is absent in CHC17 and coincides with the region on CHC17 that binds the regulatory light-chain subunit. These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions.

Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle

There is growing evidence that 1,25-dihydroxyvitamin D-3 is involved in normal brain development. The aim of this study was to examine the impact of prenatal and postnatal hypovitaminosis D on prepulse inhibition (PPI) of acoustic startle in adult rats. We compared six groups of rats: control rats with normal vitamin D throughout life and normal litter size (Litter); control rats with normal vitamin D but with a reduced litter size of two (Control); offspring from reduced litters of vitamin D deplete mothers who were repleted at birth (Birth), repleted at weaning (Weaning) or remained on a deplete diet until 10 weeks of age (Life); or control rats that were placed on a vitamin D-deficient diet from 5 to 10 weeks of age (Adult). All rats were tested in acoustic startle chambers at 5 and 10 weeks of age for acoustic startle responses and for PPI. There were no significant group differences at 5 weeks of age on the acoustic startle response or on PPI. At 10 weeks of age, rats in the Life group only had impaired PPI despite having normal acoustic startle responses. We conclude that combined prenatal and chronic postnatal hypovitaminosis D, but not early life hypovitaminosis D, alters PPI. (C) 2004 Elsevier Inc. All rights reserved.

An evaluation of a telephone-based postnatal support intervention for infant feeding in a regional Australian city

Background: Postnatal breastfeeding support in the form of home visits is difficult to accommodate in regional Australia, where hospitals often deal with harsh economic constraints in a context where they are required to provide services to geographically, dispersed consumers. This study evaluated a predominately telephone-based support service called the Infant Feeding Support Service. Methods: A prospective cohort design was used to compare data for 696 women giving birth in two regional hospitals (one public, one private) and participating in the support service between January and July 2003 with data from a cohort of 625 women who gave birth in those hospitals before the introduction of the support service. Each mother participating in the support service was assigned a lactation consultant. First contact occurred 48 hours after discharge, and approximately it weekly thereafter for 4 it weeks. Breastfeeding duration was measured at 3 months postpartum. Results: For women from the private hospital, the support service improved exclusive breastfeeding duration to 4.5 weeks postpartum, but these improvements were not evident at 3 months postpartum. No effects were observed for mothers from the public hospital. Quantitative and qualitative data demonstrated high levels of client satisfaction with the support service. Conclusions: This small-scale, predominately telephone-based intervention provided significant, although apparently context-sensitive, improvements to exclusive breastfeeding duration.

In utero and postnatal maternal smoking and asthma in adolescence

Background: Asthma in early childhood has been associated with maternal smoking during pregnancy and parental smoking soon after birth. However, less is known about these exposures and the development of asthma symptoms in adolescence. Methods: Data were taken from the Mater University Study, of Pregnancy, a large birth cohort study of mothers and children enrolled in Brisbane, Australia, beginning in 1981. Smoking was assessed at 2 stages during pregnancy and at the 6-month and 5-year follow-up visits. Asthma was assessed from maternal reports that were provided when the child was age 14 years. We conducted multivariable multinomial logistic regression analyses to assess the effect of maternal smoking on asthma symptoms. Results: There was a strong sex interaction such that girls whose mothers had smoked heavily (20 or more cigarettes per day) in pregnancy and at the 6-month follow up had increased odds of experiencing asthma symptoms at age 14 (odds ratio = 1.96; 95% confidence interval = 1.25-3.08). The contribution of heavy smoking during pregnancy appeared to be stronger than heavy smoking after the birth. No similar associations were seen for boys. Conclusion: Female adolescents whose mothers smoked heavily during the fetal period and the early months of life have increased risk of asthma symptoms in adolescence. In utero exposure to heavy smoking was found to have a stronger effect than postnatal environmental tobacco exposure.

Postnatal developmental expression of the PDZ scaffolds Na+-H+ exchanger regulatory factors 1 and 2 in the rat cochlea

Sensory transduction in the mammalian cochlea requires the maintenance of specialized fluid compartments with distinct ionic compositions. This is achieved by the concerted action of diverse ion channels and transporters, some of which can interact with the PDZ scaffolds, Na+-H+ exchanger regulatory factors 1 and 2 (NHERF-1, NHERF-2). Here, we report that NHERF-1 and NHERF-2 are widely expressed in the rat cochlea, and that their expression is developmentally regulated. Reverse transcription/polymerase chain reaction (RT-PCR) and Western blotting initially confirmed the RNA and protein expression of NHERFs. We then performed immunohistochemistry on cochlea during various stages of postnatal development. Prior to the onset of hearing (P8), NHERF-1 immunolabeling was prominently polarized to the apical membrane of cells lining the endolymphatic compartment, including the stereocilia and cuticular plates of the inner and outer hair cells, marginal cells of the stria vascularis, Reissner's epithelia, and tectorial membrane. With maturation (P21, P70), NHERF-1 immunolabeling was reduced in the above structures, whereas labeling increased in the apical membrane of the interdental cells of the spiral limbus and the inner and outer sulcus cells, Hensen's cells, the inner and outer pillar cells, Deiters cells, the inner border cells, spiral ligament fibrocytes, and spiral ganglion neurons (particularly type II). NHERF-1 expression in strial basal and intermediate cells was persistent. NHERF-2 immunolabeling was similar to that for NHERF-1 during postnatal development, with the exception of expression in the synaptic regions beneath the outer hair cells. NHERF-1 and NHERF-2 co-localized with glial fibrillary acidic protein and vimentin in glia. The cochlear localization of NHERF scaffolds suggests that they play important roles in the developmental regulation of ion transport, homeostasis, and auditory neurotransmission.

Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice

Sox7, Sox17 and Sox18 constitute group F of the Sox family of HMG box transcription factor genes. Dominant-negative mutations in Sox18 underlie the cardiovascular defects observed in ragged mutant mice. By contrast, Sox18(-/-) mice are viable and fertile, and display no appreciable anomaly in their vasculature, suggesting functional compensation by the two other SoxF genes. Here, we provide direct evidence for redundant function of Sox17 and Sox18 in postnatal neovascularization by generating Sox17(+/-)-Sox18(-/-) double mutant mice. Whereas Sox18(-/-) and Sox17(+/-)-Sox18(+/)-mice showed no vascular defects, approximately half of the Sox17(+/-)-Sox18(-/-) pups died before postnatal day 21 (P21). They showed reduced neovascularization in the liver sinusoids and kidney outer medulla vasa recta at P7, which most likely caused the ischemic necrosis observed by P14 in hepatocytes and renal tubular epithelia. Those that survived to adulthood showed similar, but milder, vascular anomalies in both liver and kidney, and females were infertile with varying degrees of vascular abnormalities in the reproductive organs. These anomalies corresponded with sites of expression of Sox7 and Sox17 in the developing postnatal vasculature. In vitro angiogenesis assays, using primary endothelial cells isolated from the P7 livers, showed that the Sox17(+/-)-Sox18(-/-)endothelial cells were defective in endothelial sprouting and remodeling of the vasculature in a phenotype-dependent manner. Therefore, our findings indicate that Sox17 and Sox18, and possibly all three SoxF genes, are cooperatively involved in mammalian vascular development.

Adult cortical plasticity depends on an early postnatal critical period

Development of the cerebral cortex is influenced by sensory experience during distinct phases of postnatal development known as critical periods. Disruption of experience during a critical period produces neurons that lack specificity for particular stimulus features, such as location in the somatosensory system. Synaptic plasticity is the agent by which sensory experience affects cortical development. Here, we describe, in mice, a developmental critical period that affects plasticity itself. Transient neonatal disruption of signaling via the C-terminal domain of "disrupted in schizophrenia 1" (DISC1)-a molecule implicated in psychiatric disorders-resulted in a lack of long-term potentiation (LTP) (persistent strengthening of synapses) and experience-dependent potentiation in adulthood. Long-term depression (LTD) (selective weakening of specific sets of synapses) and reversal of LTD were present, although impaired, in adolescence and absent in adulthood. These changes may form the basis for the cognitive deficits associated with mutations in DISC1 and the delayed onset of a range of psychiatric symptoms in late adolescence.

Appetite regulatory mechanisms and food intake in mice are sensitive to mismatch in diets between pregnancy and postnatal periods

Human and animal studies suggest that obesity in adulthood may have its origins partly during prenatal development. One of the underlying causes of obesity is the perturbation of hypothalamic mechanisms controlling appetite. We determined mRNA levels of genes that regulate appetite, namely neuropeptide Y (NPY), pro-opiomelanocortin (POMC) and the leptin receptor isoform Ob-Rb, in the hypothalamus of adult mouse offspring from pregnant dams fed a protein-restricted diet, and examined whether mismatched post-weaning high-fat diet altered further expression of these gene transcripts. Pregnant MF1 mice were fed either normal protein (C, 18% casein) or protein-restricted (PR, 9% casein) diet throughout pregnancy. Weaned offspring were fed to adulthood a high-fat (HF; 45% kcal fat) or standard chow (21% kcal fat) diet to generate the C/HF, C/C, PR/HF and PR/C groups. Food intake and body weight were monitored during this period. Hypothalamic tissues were collected at 16 weeks of age for analysis of gene expression by real time RT-PCR. All HF-fed offspring were observed to be heavier vs. C groups regardless of the maternal diet during pregnancy. In the PR/HF males, but not in females, daily energy intake was reduced by 20% vs. the PR/C group (p <0.001). In PR/HF males, hypothalamic mRNA levels were lower vs. the PR/C group for NPY (p <0.001) and Ob-Rb (p <0.05). POMC levels were similar in all groups. In females, mRNA levels for these transcripts were similar in all groups. Our results suggest that adaptive changes during prenatal development in response to maternal dietary manipulation may have long-term sex-specific consequences on the regulation of appetite and metabolism following post-weaning exposure to an energy-rich nutritional environment. © 2008 Elsevier B.V. All rights reserved.

Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure

A key factor in the use of assisted reproductive technologies (ART) for diverse species is the safety of procedures for long-term health. By using a mouse model, we have investigated the effect of in vitro culture and embryo transfer (ET) of superovulated embryos on postnatal growth and physiological activity compared with that of embryos developing in vivo. Embryo culture from two-cell to blastocyst stages in T6 medium either with or without a protein source reduced blastocyst trophectoderm and inner cell mass cell number compared with that of embryos developing in vivo. Embryo culture and ET had minimal effects on postnatal growth when compared with in vivo development with an equivalent litter size. However, embryo culture, and to a lesser extent ET, led to an enhanced systolic blood pressure at 21 weeks compared with in vivo development independent of litter size, maternal origin, or body weight. Moreover, activity of enzymatic regulators of cardiovascular and metabolic physiology, namely, serum angiotensin-converting enzyme and the gluconeogenesis controller, hepatic phosphoeno/pyruvate carboxykinase, were significantly elevated in response to embryo culture and/or ET in female offspring at 27 weeks, independent of maternal factors and postnatal growth. These animal data indicate that postnatal physiological criteria important in cardiovascular and metabolic health may be more sensitive to routine ART procedures than growth. © 2007 by The National Academy of Sciences of the USA.

The influence of mouse Ped gene expression on postnatal development

The Ped (preimplantation embryo development) gene, whose product is Qa-2 protein, is correlated with a faster rate of preimplantation development (Ped fast phenotype) in mice that express Qa-2 protein compared with mice with an absence of Qa-2 protein (Ped slow phenotype). In the current study, we have used two congenic mouse strains differentially expressing the Ped gene, strain B6.K1 (Ped slow; Qa-2 negative) and strain B6.K2 (Ped fast; Qa-2 positive), to investigate the effects of Ped gene expression on postnatal growth profiles, systolic blood pressure and adult organ allometry. At birth, B6.K1 mice were moderately lighter than B6.K2 mice. B6.K1 mice became heavier during postnatal life (P