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Sample records for postnatal plp promoter

  1. 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.

  2. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    SciTech Connect

    Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun

    2015-04-03

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

  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. Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.

    PubMed

    Kostallari, Enis; Baba-Amer, Yasmine; Alonso-Martin, Sonia; Ngoh, Pamela; Relaix, Frederic; Lafuste, Peggy; Gherardi, Romain K

    2015-04-01

    The satellite cells, which serve as adult muscle stem cells, are both located beneath myofiber basement membranes and closely associated with capillary endothelial cells. We observed that 90% of capillaries were associated with pericytes in adult mouse and human muscle. During post-natal growth, newly formed vessels with their neuroglial 2 proteoglycan (NG2)-positive pericytes became progressively associated with the post-natal muscle stem cells, as myofibers increased in size and satellite cells entered into quiescence. In vitro, human muscle-derived pericytes promoted myogenic cell differentiation through insulin-like growth factor 1 (IGF1) and myogenic cell quiescence through angiopoietin 1 (ANGPT1). Diphtheria toxin-induced ablation of muscle pericytes in growing mice led both to myofiber hypotrophy and to impaired establishment of stem cells quiescence. Similar effects were observed following conditional in vivo deletion of pericyte Igf1 and Angpt1 genes, respectively. Our data therefore demonstrate that, by promoting post-natal myogenesis and stem cell quiescence, pericytes play a key role in the microvascular niche of satellite cells.

  5. Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation

    PubMed Central

    Stark, Danny A.; Coffey, Nathan J.; Pancoast, Hannah R.; Arnold, Laura L.; Walker, J. Peyton D.; Vallée, Joanne; Robitaille, Richard; Garcia, Michael L.

    2015-01-01

    Each adult mammalian skeletal muscle has a unique complement of fast and slow myofibers, reflecting patterns established during development and reinforced via their innervation by fast and slow motor neurons. Existing data support a model of postnatal "matching" whereby predetermined myofiber type identity promotes pruning of inappropriate motor axons, but no molecular mechanism has yet been identified. We present evidence that fiber type–specific repulsive interactions inhibit innervation of slow myofibers by fast motor axons during both postnatal maturation of the neuromuscular junction and myofiber reinnervation after injury. The repulsive guidance ligand ephrin-A3 is expressed only on slow myofibers, whereas its candidate receptor, EphA8, localizes exclusively to fast motor endplates. Adult mice lacking ephrin-A3 have dramatically fewer slow myofibers in fast and mixed muscles, and misexpression of ephrin-A3 on fast myofibers followed by denervation/reinnervation promotes their respecification to a slow phenotype. We therefore conclude that Eph/ephrin interactions guide the fiber type specificity of neuromuscular interactions during development and adult life. PMID:26644518

  6. Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation.

    PubMed

    Stark, Danny A; Coffey, Nathan J; Pancoast, Hannah R; Arnold, Laura L; Walker, J Peyton D; Vallée, Joanne; Robitaille, Richard; Garcia, Michael L; Cornelison, D D W

    2015-12-07

    Each adult mammalian skeletal muscle has a unique complement of fast and slow myofibers, reflecting patterns established during development and reinforced via their innervation by fast and slow motor neurons. Existing data support a model of postnatal "matching" whereby predetermined myofiber type identity promotes pruning of inappropriate motor axons, but no molecular mechanism has yet been identified. We present evidence that fiber type-specific repulsive interactions inhibit innervation of slow myofibers by fast motor axons during both postnatal maturation of the neuromuscular junction and myofiber reinnervation after injury. The repulsive guidance ligand ephrin-A3 is expressed only on slow myofibers, whereas its candidate receptor, EphA8, localizes exclusively to fast motor endplates. Adult mice lacking ephrin-A3 have dramatically fewer slow myofibers in fast and mixed muscles, and misexpression of ephrin-A3 on fast myofibers followed by denervation/reinnervation promotes their respecification to a slow phenotype. We therefore conclude that Eph/ephrin interactions guide the fiber type specificity of neuromuscular interactions during development and adult life.

  7. 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.

  8. Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex.

    PubMed

    Chattopadhyaya, Bidisha; Baho, Elie; Huang, Z Josh; Schachner, Melitta; Di Cristo, Graziella

    2013-04-03

    GABAergic basket interneurons form perisomatic synapses, which are essential for regulating neural networks, and their alterations are linked to various cognitive dysfunction. Maturation of basket synapses in postnatal cortex is activity dependent. In particular, activity-dependent downregulation of polysialiac acid carried by the neural cell adhesion molecule (NCAM) regulates the timing of their maturation. Whether and how NCAM per se affects GABAergic synapse development is unknown. Using single-cell genetics to knock out NCAM in individual basket interneurons in mouse cortical slice cultures, at specific developmental time periods, we found that NCAM loss during perisomatic synapse formation impairs the process of basket cell axonal branching and bouton formation. However, loss of NCAM once the synapses are already formed did not show any effect. We further show that NCAM120 and NCAM140, but not the NCAM180 isoform, rescue the phenotype. Finally, we demonstrate that a dominant-negative form of Fyn kinase mimics, whereas a constitutively active form of Fyn kinase rescues, the effects of NCAM knockdown. Altogether, our data suggest that NCAM120/NCAM140-mediated Fyn activation promotes GABAergic synapse maturation in postnatal cortex.

  9. Targeted Deletion of the Antisilencer/Enhancer (ASE) Element from Intron 1 of the Myelin Proteolipid Protein Gene (Plp1) in Mouse Reveals that the Element Is Dispensable for Plp1 Expression in Brain during Development and Remyelination

    PubMed Central

    Pereira, Glauber B.; Meng, Fanxue; Kockara, Neriman T.; Yang, Baoli; Wight, Patricia A.

    2012-01-01

    Myelin proteolipid protein gene (Plp1) expression is temporally regulated in brain, which peaks during the active myelination period of CNS development. Previous studies with Plp1-lacZ transgenic mice demonstrated that (mouse) Plp1 intron 1 DNA is required for high levels of expression in oligodendrocytes. Deletion-transfection analysis revealed the intron contains a single positive regulatory element operative in the N20.1 oligodendroglial cell line, which was named ASE (antisilencer/enhancer) based on its functional properties in these cells. To investigate the role of the ASE in vivo, the element was deleted from the native gene in mouse using a Cre/lox strategy. While removal of the ASE from Plp1-lacZ constructs profoundly decreased expression in transfected oligodendroglial cell lines (N20.1 and Oli-neu), the element was dispensable to achieve normal levels of Plp1 gene expression in mouse during development (except perhaps at postnatal day 15) and throughout the remyelination period following cuprizone-induced (acute) demyelination. Thus, it is possible that the ASE is nonfunctional in vivo, or that loss of the ASE from the native gene in mouse can be compensated for by the presence of other regulatory elements within the Plp1 gene. PMID:23157328

  10. 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.

  11. Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone.

    PubMed

    Relucio, Jenne; Menezes, Michael J; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Colognato, Holly

    2012-10-01

    The laminin family of extracellular matrix proteins are expressed broadly during embryonic brain development, but are enriched at ventricular and pial surfaces where laminins mediate radial glial attachment during corticogenesis. In the adult brain, however, laminin distribution is restricted, yet is found within the vascular basal lamina and associated fractones of the ventricular zone (VZ)-subventricular zone (SVZ) stem cell niche, where laminins regulate adult neural progenitor cell proliferation. It remains unknown, however, if laminins regulate the wave of oligodendrogenesis that occurs in the neonatal/early postnatal VZ-SVZ. Here we report that Lama2, the gene that encodes the laminin α2-subunit, regulates postnatal oligodendrogenesis. At birth, Lama2-/- mice had significantly higher levels of dying oligodendrocyte progenitor cells (OPCs) in the OPC germinal zone of the dorsal SVZ. This translated into fewer OPCs, both in the dorsal SVZ well as in an adjacent developing white matter tract, the corpus callosum. In addition, intermediate progenitor cells that give rise to OPCs in the Lama2-/- VZ-SVZ were mislocalized and proliferated nearer to the ventricle surface. Later, delays in oligodendrocyte maturation (with accompanying OPC accumulation), were observed in the Lama2-/- corpus callosum, leading to dysmyelination by postnatal day 21. Together these data suggest that prosurvival laminin interactions in the developing postnatal VZ-SVZ germinal zone regulate the ability, or timing, of oligodendrocyte production to occur appropriately.

  12. TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation.

    PubMed

    Alpern, Daniil; Langer, Diana; Ballester, Benoit; Le Gras, Stephanie; Romier, Christophe; Mengus, Gabrielle; Davidson, Irwin

    2014-09-10

    The functions of the TAF subunits of mammalian TFIID in physiological processes remain poorly characterised. In this study, we describe a novel function of TAFs in directing genomic occupancy of a transcriptional activator. Using liver-specific inactivation in mice, we show that the TAF4 subunit of TFIID is required for post-natal hepatocyte maturation. TAF4 promotes pre-initiation complex (PIC) formation at post-natal expressed liver function genes and down-regulates a subset of embryonic expressed genes by increased RNA polymerase II pausing. The TAF4-TAF12 heterodimer interacts directly with HNF4A and in vivo TAF4 is necessary to maintain HNF4A-directed embryonic gene expression at post-natal stages and promotes HNF4A occupancy of functional cis-regulatory elements adjacent to the transcription start sites of post-natal expressed genes. Stable HNF4A occupancy of these regulatory elements requires TAF4-dependent PIC formation highlighting that these are mutually dependent events. Local promoter-proximal HNF4A-TFIID interactions therefore act as instructive signals for post-natal hepatocyte differentiation.

  13. Expression of a novel member of the ATP1G1/PLM/MAT8 family, phospholemman-like protein (PLP) gene, in the developmental process of mouse cerebellum.

    PubMed

    Saito, S; Matoba, R; Kato, K; Matsubara, K

    2001-11-28

    We have identified a new member of the ATP1G1/PLM/MAT8 family, named phospholemman-like protein (PLP), from a mouse cerebellum cDNA library. The family consists of small transmembrane proteins that modulate the activities of some ion channels. The deduced amino acid sequence of PLP consists of 93 residues that contain the ATP1G1/PLM/MAT8 motif and a single transmembrane domain, and is most similar to the sequence of mouse phospholemman. In situ hybridization analysis showed that the PLP gene is highly expressed in cerebellar granule cells. PLP expression is elevated in the postnatal developing cerebellum. Thus, it may be implicated in the proliferation, differentiation, and axon elongation of granule cells as they mature and migrate to the internal granule layer.

  14. Wnt activation followed by Notch inhibition promotes mitotic hair cell regeneration in the postnatal mouse cochlea

    PubMed Central

    Li, Wenyan; Chen, Yan; Zhang, Shasha; Tang, Mingliang; Sun, Shan; Chai, Renjie; Li, Huawei

    2016-01-01

    Hair cell (HC) loss is the main cause of permanent hearing loss in mammals. Previous studies have reported that in neonatal mice cochleae, Wnt activation promotes supporting cell (SC) proliferation and Notch inhibition promotes the trans-differentiation of SCs into HCs. However, Wnt activation alone fails to regenerate significant amounts of new HCs, Notch inhibition alone regenerates the HCs at the cost of exhausting the SC population, which leads to the death of the newly regenerated HCs. Mitotic HC regeneration might preserve the SC number while regenerating the HCs, which could be a better approach for long-term HC regeneration. We present a two-step gene manipulation, Wnt activation followed by Notch inhibition, to accomplish mitotic regeneration of HCs while partially preserving the SC number. We show that Wnt activation followed by Notch inhibition strongly promotes the mitotic regeneration of new HCs in both normal and neomycin-damaged cochleae while partially preserving the SC number. Lineage tracing shows that the majority of the mitotically regenerated HCs are derived specifically from the Lgr5+ progenitors with or without HC damage. Our findings suggest that the co-regulation of Wnt and Notch signaling might provide a better approach to mitotically regenerate HCs from Lgr5+ progenitor cells. PMID:27564256

  15. Policy for Promotion of Women's Mental Health: Insight from Analysis of Policy on Postnatal Depression in Mexico.

    PubMed

    Place, Jean Marie S; Billings, Deborah L; Frongillo, Edward A; Blake, Christine E; Mann, Joshua R; deCastro, Filipa

    2016-03-01

    This article critically examines federal, state and facility-level policies, as well as clinical practice guidelines regarding postnatal depression in Mexico. Thirteen documents including national health plans, national action plans, federal and state laws and regulations, clinical practice guidelines, and public-sector healthcare facility policies were collected and evaluated according to whether they included a statement of intent and/or actions related to the care of women at risk for or experiencing postnatal depression. While postnatal depression is included in several policies in Mexico, it is not addressed in ways that guide actions to manage postnatal depression. Specific direction on postnatal depression in policies would bridge a gap in maternal mental healthcare given that medication, treatment, and timing of interventions is unique in the postpartum context.

  16. Type I TARPs promote dendritic growth of early postnatal neocortical pyramidal cells in organotypic cultures.

    PubMed

    Hamad, Mohammad I K; Jack, Alexander; Klatt, Oliver; Lorkowski, Markus; Strasdeit, Tobias; Kott, Sabine; Sager, Charlotte; Hollmann, Michael; Wahle, Petra

    2014-04-01

    The ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptors (AMPARs) have been implicated in the establishment of dendritic architecture. The transmembrane AMPA receptor regulatory proteins (TARPs) regulate AMPAR function and trafficking into synaptic membranes. In the current study, we employ type I and type II TARPs to modulate expression levels and function of endogenous AMPARs and investigate in organotypic cultures (OTCs) of rat occipital cortex whether this influences neuronal differentiation. Our results show that in early development [5-10 days in vitro (DIV)] only the type I TARP γ-8 promotes pyramidal cell dendritic growth by increasing spontaneous calcium amplitude and GluA2/3 expression in soma and dendrites. Later in development (10-15 DIV), the type I TARPs γ-2, γ-3 and γ-8 promote dendritic growth, whereas γ-4 reduced dendritic growth. The type II TARPs failed to alter dendritic morphology. The TARP-induced dendritic growth was restricted to the apical dendrites of pyramidal cells and it did not affect interneurons. Moreover, we studied the effects of short hairpin RNA-induced knockdown of endogenous γ-8 and showed a reduction of dendritic complexity and amplitudes of spontaneous calcium transients. In addition, the cytoplasmic tail (CT) of γ-8 was required for dendritic growth. Single-cell calcium imaging showed that the γ-8 CT domain increases amplitude but not frequency of calcium transients, suggesting a regulatory mechanism involving the γ-8 CT domain in the postsynaptic compartment. Indeed, the effect of γ-8 overexpression was reversed by APV, indicating a contribution of NMDA receptors. Our results suggest that selected type I TARPs influence activity-dependent dendritogenesis of immature pyramidal neurons.

  17. Immune responses against chimeric DNA and protein vaccines composed of plpEN-OmpH and PlpEC-OmpH from Pasteurella multocida A:3 in mice.

    PubMed

    Okay, Sezer; Ozcengiz, Erkan; Ozcengiz, Gülay

    2012-12-01

    Pasteurella multocida is a pathogenic bacterium causing many diseases that are of significant economic importance to livestock industries. Outer membrane protein H (ompH) gene and two fragments of Pasteurella lipoprotein E (plpE) gene, namely plpEN and plpEC, were cloned from P. multocida A:3. Three DNA vaccine formulations, namely pCMV-ompH, pCMV-plpEN-ompH and pCMV-plpEC-ompH and two protein-based prototype vaccines, alum adjuvanted PlpEN-OmpH and PlpEC-OmpH, were generated. Antibody levels were induced in mice vaccinated with chimeric DNA or protein vaccines. A significant (p < 0.05) increase in serum IFN-g titer was obtained by vaccination with 100 μg of pCMV-ompH, pCMV-plpEC-ompH and PlpEC-OmpH. DNA vaccines did not provide protection upon intraperitoneal challenge with 10 LD50 of live P. multocida A:3. However, 40% protection was conferred by 100 μg of PlpEC-OmpH which was not statistically significant. These results showed that plpEN-ompH and plpEC-ompH chimeric DNA vaccines and alum adjuvanted PlpEN-OmpH or PlpEC-OmpH protein vaccines were immunogenic but not protective against P. multocida A:3 in mice. Prime-boost strategies, i.e. priming with DNA vaccines and boost with protein formulations or different adjuvants can be utilized to obtain significant protection.

  18. 13 CFR 120.453 - Responsibilities of PLP Lenders for servicing and liquidating 7(a) loans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Responsibilities of PLP Lenders for servicing and liquidating 7(a) loans. 120.453 Section 120.453 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Lenders Preferred Lenders Program (plp) § 120.453...

  19. Expression of recombinant human lysozyme in transgenic chicken promotes the growth of Bifidobacterium in the intestine and improves postnatal growth of chicken.

    PubMed

    Wang, Hai; Wu, Hongping; Wang, Kejun; Cao, Zhichen; Yu, Kun; Lian, Ling; Lian, Zhengxing

    2016-12-01

    Lysozyme is one kind of antimicrobial proteins and often used as feed additive which can defend against pathogenic bacteria and enhance immune function of animals. In this study, we have injected the lentiviral vector expressing recombinant human lysozyme (rhLZ) gene into the blastoderm of chicken embryo to investigate the effect of recombinant human lysozyme on postnatal intestinal microbiota distribution and growth performance of chicken. Successfully, we generated 194 transgenic chickens identified by Southern blot with a positive transgenic rate of 24%. The average concentration of rhLZ was 29.90 ± 6.50 μg/mL in the egg white. Lysozyme in egg white of transgenic chickens had a significantly higher antibacterial activity than those of non-transgenic chickens by lysoplate assay (P < 0.05). The feces of transgenic and non-transgenic chickens were collected and five types of bacteria (Lactobacillus, Salmonella, Bifidobacterium, Staphylococcus aureus and Escherichia coli) were isolated and cultured to detect the impact of rhLZ on gut microbiota. Among the five bacteria, the number of Bifidobacterium in the intestine of those transgenic was significantly increased (P < 0.05). Moreover, the growth traits of the transgenic and non-transgenic chickens were analyzed. It was found that the 6-week shank length, 6-week weight and 18-week weight of transgenic chickens were significantly increased than that of non-transgenic chickens. The results demonstrated that rhLZ-transgenic chicken could promote the growth of Bifidobacterium in the intestine and improve the postnatal growth of chicken.

  20. The lateral membrane organization and dynamics of myelin proteins PLP and MBP are dictated by distinct galactolipids and the extracellular matrix.

    PubMed

    Ozgen, Hande; Schrimpf, Waldemar; Hendrix, Jelle; de Jonge, Jenny C; Lamb, Don C; Hoekstra, Dick; Kahya, Nicoletta; Baron, Wia

    2014-01-01

    In the central nervous system, lipid-protein interactions are pivotal for myelin maintenance, as these interactions regulate protein transport to the myelin membrane as well as the molecular organization within the sheath. To improve our understanding of the fundamental properties of myelin, we focused here on the lateral membrane organization and dynamics of peripheral membrane protein 18.5-kDa myelin basic protein (MBP) and transmembrane protein proteolipid protein (PLP) as a function of the typical myelin lipids galactosylceramide (GalC), and sulfatide, and exogenous factors such as the extracellular matrix proteins laminin-2 and fibronectin, employing an oligodendrocyte cell line, selectively expressing the desired galactolipids. The dynamics of MBP were monitored by z-scan point fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), while PLP dynamics in living cells were investigated by circular scanning FCS. The data revealed that on an inert substrate the diffusion rate of 18.5-kDa MBP increased in GalC-expressing cells, while the diffusion coefficient of PLP was decreased in sulfatide-containing cells. Similarly, when cells were grown on myelination-promoting laminin-2, the lateral diffusion coefficient of PLP was decreased in sulfatide-containing cells. In contrast, PLP's diffusion rate increased substantially when these cells were grown on myelination-inhibiting fibronectin. Additional biochemical analyses revealed that the observed differences in lateral diffusion coefficients of both proteins can be explained by differences in their biophysical, i.e., galactolipid environment, specifically with regard to their association with lipid rafts. Given the persistence of pathological fibronectin aggregates in multiple sclerosis lesions, this fundamental insight into the nature and dynamics of lipid-protein interactions will be instrumental in developing myelin regenerative strategies.

  1. Further genotype-phenotype correlation emerging from two families with PLP1 exon 4 skipping.

    PubMed

    Biancheri, Roberta; Grossi, Serena; Regis, Stefano; Rossi, Andrea; Corsolini, Fabio; Rossi, Daniela Paola; Cavalli, Pietro; Severino, Mariasavina; Filocamo, Mirella

    2014-03-01

    Proteolipid protein 1 (PLP1) gene-related disorders due to mutations in the PLP1 include a wide spectrum of X-linked disorders ranging from severe connatal Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). Duplications, deletions or point mutations in coding and noncoding regions of the PLP1 gene may occur. We report the clinical, neuroradiologic and molecular findings in six patients from two unrelated families. The affected males showed severe mental retardation, spastic tetraparesis, inability of walking and pes cavus at onset in early infancy. Brain magnetic resonance imaging (MRI) showed hypomyelination and brain atrophy. Nystagmus was never observed. The affected females showed adult-onset progressive spastic paraparesis leading to wheel-chair dependency and subtle white matter changes on brain MRI. Molecular studies in the two families identified two different intronic mutations, the novel c.622+2T>C and the known c.622+1G>A, leading to the skipping of PLP1-exon 4. The clinical presentation of the affected males did not consistently fit in any of the PLP1-related disorder subtypes (i.e., connatal or classic PMD, SPG2 and 'PLP1 null syndrome'), and in addition, the carrier females were symptomatic despite the severe clinical picture of their respective probands. This study provides new insight into the genotype-phenotype correlations of patients with PLP1 splice-site mutations.

  2. Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype

    PubMed Central

    Kuzdas-Wood, Daniela; Irschick, Regina; Theurl, Markus; Malsch, Philipp; Mair, Norbert; Mantinger, Christine; Wanschitz, Julia; Klimaschewski, Lars; Poewe, Werner; Stefanova, Nadia; Wenning, Gregor K.

    2015-01-01

    Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with (oligodendro-)glial cytoplasmic α-synuclein (α-syn) inclusions (GCIs). Peripheral neuropathies have been reported in up to 40% of MSA patients, the cause remaining unclear. In a transgenic MSA mouse model featuring GCI-like inclusion pathology based on PLP-promoter driven overexpression of human α-syn in oligodendroglia motor and non-motor deficits are associated with MSA-like neurodegeneration. Since α-syn is also expressed in Schwann cells we aimed to investigate whether peripheral nerves are anatomically and functionally affected in the PLP-α-syn MSA mouse model. Results To this end, heat/cold as well as mechanical sensitivity tests were performed. Furthermore, in vivo and ex vivo nerve conduction and the G-ratios of the sciatic nerve were analyzed, and thermosensitive ion channel mRNA expression in dorsal root ganglia (DRG) was assessed. The presence of human α-syn in Schwann cells was associated with subtle behavioral impairments. The G-ratio of the sciatic nerve, the conduction velocity of myelinated and unmyelinated primary afferents and the expression of thermosensitive ion channels in the sensory neurons, however, were similar to wildtype mice. Conclusion Our results suggest that the PNS appears to be affected by Schwann cell α-syn deposits in the PLP-α-syn MSA mouse model. However, there was no consistent evidence for functional PNS perturbations resulting from such α-syn aggregates suggesting a more central cause of the observed behavioral abnormalities. Nonetheless, our results do not exclude a causal role of α-syn in the pathogenesis of MSA associated peripheral neuropathy. PMID:26496712

  3. MAL Is a Regulator of the Recruitment of Myelin Protein PLP to Membrane Microdomains

    PubMed Central

    Bijlard, Marjolein; de Jonge, Jenny C.; Klunder, Bert; Nomden, Anita; Hoekstra, Dick; Baron, Wia

    2016-01-01

    In oligodendrocytes (OLGs), an indirect, transcytotic pathway is mediating transport of de novo synthesized PLP, a major myelin specific protein, from the apical-like plasma membrane to the specialized basolateral-like myelin membrane to prevent its premature compaction. MAL is a well-known regulator of polarized trafficking in epithelial cells, and given its presence in OLGs it was therefore of interest to investigate whether MAL played a similar role in PLP transport in OLGs, taking into account its timely expression in these cells. Our data revealed that premature expression of mCherry-MAL in oligodendrocyte progenitor cells interfered with terminal OLG differentiation, although myelin membrane formation per se was not impaired. In fact, also PLP transport to myelin membranes via the cell body plasma membrane was unaffected. However, the typical shift of PLP from TX-100-insoluble membrane domains to CHAPS-resistant, but TX-100-soluble membrane domains, seen in the absence of MAL expression, is substantially reduced upon expression of the MAL protein. Interestingly, not only in vitro, but also in developing brain a strongly diminished shift from TX-100 resistant to TX-100 soluble domains was observed. Consistently, the MAL-expression mediated annihilation of the typical membrane microdomain shift of PLP is also reflected by a loss of the characteristic surface expression profile of conformation-sensitive anti-PLP antibodies. Hence, these findings suggest that MAL is not involved in vesicular PLP trafficking to either the plasma membrane and/or the myelin membrane as such. Rather, we propose that MAL may regulate PLP’s distribution into distinct membrane microdomains that allow for lateral diffusion of PLP, directly from the plasma membrane to the myelin membrane once the myelin sheath has been assembled. PMID:27171274

  4. Maternal dietary loads of α-tocopherol depress protein kinase C signaling and synaptic plasticity in rat postnatal developing hippocampus and promote permanent deficits in adult offspring.

    PubMed

    Betti, Michele; Ambrogini, Patrizia; Minelli, Andrea; Floridi, Alessandro; Lattanzi, Davide; Ciuffoli, Stefano; Bucherelli, Corrado; Prospero, Emilia; Frontini, Andrea; Santarelli, Lory; Baldi, Elisabetta; Benetti, Fernando; Galli, Francesco; Cuppini, Riccardo

    2011-01-01

    Vitamin E (α-tocopherol) supplementation has been tested as prophylaxis against gestational disorders associated with oxidative damage. However, recent evidence showing that high maternal α-tocopherol intake can adversely affect offspring development raises concerns on the safety of vitamin E extradosages during pregnancy. Besides acting as an antioxidant, α-tocopherol depresses cell proliferation and modulates cell signaling through inhibiting protein kinase C (PKC), a kinase that is deeply involved in neural maturation and plasticity. Possible effects of α-tocopherol loads in the maturing brain, where PKC dysregulation is associated to developmental dysfunctions, are poorly known. Here, supranutritional doses of α-tocopherol were fed to pregnant and lactating dams to evaluate the effects on PKC signaling and morphofunctional maturation in offspring hippocampus. Results showed that maternal supplementation potentiates hippocampal α-tocopherol incorporation in offspring and leads to marked decrease of PKC phosphorylation throughout postnatal maturation, accompanied by reduced phosphorylation of growth-associated protein-43 and myristoylated alanine-rich C kinase substrate, two PKC substrates involved in neural development and plasticity. Although processes of neuronal maturation, synapse formation and targeting appeared unaffected, offspring of supplemented mothers displayed a marked reduction of long-term synaptic plasticity in juvenile hippocampus. Interestingly, this impairment persisted in adulthood, when a deficit in hippocampus-dependent, long-lasting spatial memory was also revealed. In conclusion, maternal supplementation with elevated doses of α-tocopherol can influence cell signaling and synaptic plasticity in developing hippocampus and promotes permanent adverse effects in adult offspring. The present results emphasize the need to evaluate the safety of supranutritional maternal intake of α-tocopherol in humans.

  5. Control of Human PLP1 Expression Through Transcriptional Regulatory Elements and Alternatively Spliced Exons in Intron 1

    PubMed Central

    Hamdan, Hamdan; Kockara, Neriman T.; Jolly, Lee Ann; Haun, Shirley

    2015-01-01

    *These authors contributed equally to this work.Although the myelin proteolipid protein gene (PLP1) encodes the most abundant protein in central nervous system (CNS) myelin, not much is known about the mechanisms that govern expression of the human gene (hPLP1). Much more is known about the processes that regulate Plp1 gene expression in rodents. From studies with Plp1-lacZ transgenic mice, it was determined that the first intron of mouse Plp1 (mPlp1) is required to attain high levels of expression in brain, concurrent with the active myelination period. Other studies have suggested that within mPlp1 intron 1 (>8 kb) lie several regions with enhancer-like activity. To test whether these sequences (and possibly others) in hPLP1 intron 1 are functional, deletion-transfection analysis was performed with hPLP1-lacZ constructs that contain various portions of the intron, or lack it altogether. Results presented here demonstrate the importance of hPLP1 intron 1 in achieving maximal levels of expression in the immortalized oligodendroglial cell line, Oli-neu. Deletion analysis indicates that the intron contains multiple positive regulatory elements which are active in Oli-neu cells. Some of these elements appear to be functionally conserved between human and mouse, while others are not. Furthermore, our studies demonstrate that multiple splice variants can be formed due to inclusion of extra (supplementary) exons from what is classically thought of as hPLP1 intron 1. Thus, splicing of these novel exons (which are not recognized as such in mPlp1 due to lack of conserved splice sites) must utilize factors common to both human and mouse since Oli-neu cells are of mouse origin. PMID:25694552

  6. Comparative wavelet, PLP, and LPC speech recognition techniques on the Hindi speech digits database

    NASA Astrophysics Data System (ADS)

    Mishra, A. N.; Shrotriya, M. C.; Sharan, S. N.

    2010-02-01

    In view of the growing use of automatic speech recognition in the modern society, we study various alternative representations of the speech signal that have the potential to contribute to the improvement of the recognition performance. In this paper wavelet based features using different wavelets are used for Hindi digits recognition. The recognition performance of these features has been compared with Linear Prediction Coefficients (LPC) and Perceptual Linear Prediction (PLP) features. All features have been tested using Hidden Markov Model (HMM) based classifier for speaker independent Hindi digits recognition. The recognition performance of PLP features is11.3% better than LPC features. The recognition performance with db10 features has shown a further improvement of 12.55% over PLP features. The recognition performance with db10 is best among all wavelet based features.

  7. The Major Myelin-Resident Protein PLP Is Transported to Myelin Membranes via a Transcytotic Mechanism: Involvement of Sulfatide

    PubMed Central

    Ozgen, Hande; Klunder, Bert; de Jonge, Jenny C.; Nomden, Anita; Plat, Annechien; Trifilieff, Elisabeth; de Vries, Hans; Hoekstra, Dick

    2014-01-01

    Myelin membranes are sheet-like extensions of oligodendrocytes that can be considered membrane domains distinct from the cell's plasma membrane. Consistent with the polarized nature of oligodendrocytes, we demonstrate that transcytotic transport of the major myelin-resident protein proteolipid protein (PLP) is a key element in the mechanism of myelin assembly. Upon biosynthesis, PLP traffics to myelin membranes via syntaxin 3-mediated docking at the apical-surface-like cell body plasma membrane, which is followed by subsequent internalization and transport to the basolateral-surface-like myelin sheet. Pulse-chase experiments, in conjunction with surface biotinylation and organelle fractionation, reveal that following biosynthesis, PLP is transported to the cell body surface in Triton X-100 (TX-100)-resistant microdomains. At the plasma membrane, PLP transiently resides within these microdomains and its lateral dissipation is followed by segregation into 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS)-resistant domains, internalization, and subsequent transport toward the myelin membrane. Sulfatide triggers PLP's reallocation from TX-100- into CHAPS-resistant membrane domains, while inhibition of sulfatide biosynthesis inhibits transcytotic PLP transport. Taking these findings together, we propose a model in which PLP transport to the myelin membrane proceeds via a transcytotic mechanism mediated by sulfatide and characterized by a conformational alteration and dynamic, i.e., transient, partitioning of PLP into distinct membrane microdomains involved in biosynthetic and transcytotic transport. PMID:25368380

  8. Crystal structures capture three states in the catalytic cycle of a pyridoxal phosphate (PLP) synthase.

    PubMed

    Smith, Amber Marie; Brown, William Clay; Harms, Etti; Smith, Janet L

    2015-02-27

    PLP synthase (PLPS) is a remarkable single-enzyme biosynthetic pathway that produces pyridoxal 5'-phosphate (PLP) from glutamine, ribose 5-phosphate, and glyceraldehyde 3-phosphate. The intact enzyme includes 12 synthase and 12 glutaminase subunits. PLP synthesis occurs in the synthase active site by a complicated mechanism involving at least two covalent intermediates at a catalytic lysine. The first intermediate forms with ribose 5-phosphate. The glutaminase subunit is a glutamine amidotransferase that hydrolyzes glutamine and channels ammonia to the synthase active site. Ammonia attack on the first covalent intermediate forms the second intermediate. Glyceraldehyde 3-phosphate reacts with the second intermediate to form PLP. To investigate the mechanism of the synthase subunit, crystal structures were obtained for three intermediate states of the Geobacillus stearothermophilus intact PLPS or its synthase subunit. The structures capture the synthase active site at three distinct steps in its complicated catalytic cycle, provide insights into the elusive mechanism, and illustrate the coordinated motions within the synthase subunit that separate the catalytic states. In the intact PLPS with a Michaelis-like intermediate in the glutaminase active site, the first covalent intermediate of the synthase is fully sequestered within the enzyme by the ordering of a generally disordered 20-residue C-terminal tail. Following addition of ammonia, the synthase active site opens and admits the Lys-149 side chain, which participates in formation of the second intermediate and PLP. Roles are identified for conserved Asp-24 in the formation of the first intermediate and for conserved Arg-147 in the conversion of the first to the second intermediate.

  9. Late postnatal development of intrinsic and synaptic properties promotes fast and precise signaling in the dorsal nucleus of the lateral lemniscus.

    PubMed

    Ammer, J J; Grothe, B; Felmy, F

    2012-02-01

    The dorsal nucleus of the lateral lemniscus (DNLL) is an auditory brain stem structure that generates a long-lasting GABAergic output, which is important for binaural processing. Despite its importance in binaural processing, little is known about the cellular physiology and the synaptic input kinetics of DNLL neurons. To assess the relevant physiological parameters of DNLL neurons, their late postnatal developmental profile was analyzed in acute brain slices of 9- to 26-day-old Mongolian gerbils. The observed developmental changes in passive membrane and action potential (AP) properties all point toward an improvement of fast and precise signal integration in these neurons. Accordingly, synaptic glutamatergic and GABAergic current kinetics accelerate with age. The changes in intrinsic and synaptic properties contribute nearly equally to reduce the latency and jitter in AP generation and thus enhance the temporal precision of DNLL neurons. Furthermore, the size of the synaptic NMDA current is developmentally downregulated. Despite this developmental reduction, DNLL neurons display an NMDA-dependent postsynaptic amplification of AP generation, known to support high firing rates, throughout this developmental period. Taken together, our findings indicate that during late postnatal development DNLL neurons are optimized for high firing rates with high temporal precision.

  10. Three or more copies of the proteolipid protein gene PLP1 cause severe Pelizaeus-Merzbacher disease.

    PubMed

    Wolf, Nicole I; Sistermans, Erik A; Cundall, Maria; Hobson, Grace M; Davis-Williams, Angelique P; Palmer, Rodger; Stubbs, Paula; Davies, Sally; Endziniene, Milda; Wu, Yvonne; Chong, Wui K; Malcolm, Sue; Surtees, Robert; Garbern, James Y; Woodward, Karen J

    2005-04-01

    We describe five boys from different families with an atypically severe form of Pelizaeus-Merzbacher disease (PMD) who have three, and in one case, five copies of the proteolipid protein (PLP1) gene. This is the first report of more than two copies of PLP1 in PMD patients and clearly demonstrates that severe clinical symptoms are associated with increased PLP1 gene dosage. Previously, duplications, deletions and mutations of the PLP1 gene were reported to give rise to this X-linked disorder. Patients with PLP1 duplication are usually classified as having either classical or transitional PMD rather than the more rare severe connatal form. The clinical symptoms of the five patients in this study included lack of stable head control and severe mental retardation, with three having severe paroxysmal disorder and two dying before the first year of life. Gene dosage was determined using interphase FISH (fluorescence in situ hybridization) and the novel approach of multiple ligation probe amplification (MLPA). We found FISH unreliable for dosage detection above the level of a duplication and MLPA to be more accurate in determination of specific copy number. Our finding that three or more copies of the gene give rise to a more severe phenotype is in agreement with observations in transgenic mice where severity of disease increased with Plp1 gene dosage and level of overexpression. The patient with five copies of PLP1 was not more affected than those with a triplication, suggesting that there is possibly a limit to the level of severity or that other genetic factors influence the phenotype. It highlights the significance of PLP1 dosage in CNS myelinogenesis as well as the importance of accurate determination of PLP1 gene copy number in the diagnosis of PMD and carrier detection.

  11. PMD patient mutations reveal a long-distance intronic interaction that regulates PLP1/DM20 alternative splicing

    PubMed Central

    Taube, Jennifer R.; Sperle, Karen; Banser, Linda; Seeman, Pavel; Cavan, Barbra Charina V.; Garbern, James Y.; Hobson, Grace M.

    2014-01-01

    Alternative splicing of the proteolipid protein 1 gene (PLP1) produces two forms, PLP1 and DM20, due to alternative use of 5′ splice sites with the same acceptor site in intron 3. The PLP1 form predominates in central nervous system RNA. Mutations that reduce the ratio of PLP1 to DM20, whether mutant or normal protein is formed, result in the X-linked leukodystrophy Pelizaeus-Merzbacher disease (PMD). We investigated the ability of sequences throughout PLP1 intron 3 to regulate alternative splicing using a splicing minigene construct transfected into the oligodendrocyte cell line, Oli-neu. Our data reveal that the alternative splice of PLP1 is regulated by a long-distance interaction between two highly conserved elements that are separated by 581 bases within the 1071-base intron 3. Further, our data suggest that a base-pairing secondary structure forms between these two elements, and we demonstrate that mutations of either element designed to destabilize the secondary structure decreased the PLP1/DM20 ratio, while swap mutations designed to restore the structure brought the PLP1/DM20 ratio to near normal levels. Sequence analysis of intron 3 in families with clinical symptoms of PMD who did not have coding-region mutations revealed mutations that segregated with disease in three families. We showed that these patient mutations, which potentially destabilize the secondary structure, also reduced the PLP1/DM20 ratio. This is the first report of patient mutations causing disease by disruption of a long-distance intronic interaction controlling alternative splicing. This finding has important implications for molecular diagnostics of PMD. PMID:24890387

  12. Auditory Hair Cell-Specific Deletion of p27Kip1 in Postnatal Mice Promotes Cell-Autonomous Generation of New Hair Cells and Normal Hearing

    PubMed Central

    Walters, Bradley J.; Liu, Zhiyong; Crabtree, Mark; Coak, Emily; Cox, Brandon C.

    2014-01-01

    Hearing in mammals relies upon the transduction of sound by hair cells (HCs) in the organ of Corti within the cochlea of the inner ear. Sensorineural hearing loss is a widespread and permanent disability due largely to a lack of HC regeneration in mammals. Recent studies suggest that targeting the retinoblastoma (Rb)/E2F pathway can elicit proliferation of auditory HCs. However, previous attempts to induce HC proliferation in this manner have resulted in abnormal cochlear morphology, HC death, and hearing loss. Here we show that cochlear HCs readily proliferate and survive following neonatal, HC-specific, conditional knock-out of p27Kip1 (p27CKO), a tumor suppressor upstream of Rb. Indeed, HC-specific p27CKO results in proliferation of these cells without the upregulation of the supporting cell or progenitor cell proteins, Prox1 or Sox2, suggesting that they remain HCs. Furthermore, p27CKO leads to a significant addition of postnatally derived HCs that express characteristic synaptic and stereociliary markers and survive to adulthood, although a portion of the newly derived inner HCs exhibit cytocauds and lack VGlut3 expression. Despite this, p27CKO mice exhibit normal hearing as measured by evoked auditory brainstem responses, which suggests that the newly generated HCs may contribute to, or at least do not greatly detract from, function. These results show that p27Kip1 actively maintains HC quiescence in postnatal mice, and suggest that inhibition of p27Kip1 in residual HCs represents a potential strategy for cell-autonomous auditory HC regeneration. PMID:25411503

  13. Auditory hair cell-specific deletion of p27Kip1 in postnatal mice promotes cell-autonomous generation of new hair cells and normal hearing.

    PubMed

    Walters, Bradley J; Liu, Zhiyong; Crabtree, Mark; Coak, Emily; Cox, Brandon C; Zuo, Jian

    2014-11-19

    Hearing in mammals relies upon the transduction of sound by hair cells (HCs) in the organ of Corti within the cochlea of the inner ear. Sensorineural hearing loss is a widespread and permanent disability due largely to a lack of HC regeneration in mammals. Recent studies suggest that targeting the retinoblastoma (Rb)/E2F pathway can elicit proliferation of auditory HCs. However, previous attempts to induce HC proliferation in this manner have resulted in abnormal cochlear morphology, HC death, and hearing loss. Here we show that cochlear HCs readily proliferate and survive following neonatal, HC-specific, conditional knock-out of p27(Kip1) (p27CKO), a tumor suppressor upstream of Rb. Indeed, HC-specific p27CKO results in proliferation of these cells without the upregulation of the supporting cell or progenitor cell proteins, Prox1 or Sox2, suggesting that they remain HCs. Furthermore, p27CKO leads to a significant addition of postnatally derived HCs that express characteristic synaptic and stereociliary markers and survive to adulthood, although a portion of the newly derived inner HCs exhibit cytocauds and lack VGlut3 expression. Despite this, p27CKO mice exhibit normal hearing as measured by evoked auditory brainstem responses, which suggests that the newly generated HCs may contribute to, or at least do not greatly detract from, function. These results show that p27(Kip1) actively maintains HC quiescence in postnatal mice, and suggest that inhibition of p27(Kip1) in residual HCs represents a potential strategy for cell-autonomous auditory HC regeneration.

  14. Treatment of phantom limb pain (PLP) based on augmented reality and gaming controlled by myoelectric pattern recognition: a case study of a chronic PLP patient

    PubMed Central

    Ortiz-Catalan, Max; Sander, Nichlas; Kristoffersen, Morten B.; Håkansson, Bo; Brånemark, Rickard

    2014-01-01

    A variety of treatments have been historically used to alleviate phantom limb pain (PLP) with varying efficacy. Recently, virtual reality (VR) has been employed as a more sophisticated mirror therapy. Despite the advantages of VR over a conventional mirror, this approach has retained the use of the contralateral limb and is therefore restricted to unilateral amputees. Moreover, this strategy disregards the actual effort made by the patient to produce phantom motions. In this work, we investigate a treatment in which the virtual limb responds directly to myoelectric activity at the stump, while the illusion of a restored limb is enhanced through augmented reality (AR). Further, phantom motions are facilitated and encouraged through gaming. The proposed set of technologies was administered to a chronic PLP patient who has shown resistance to a variety of treatments (including mirror therapy) for 48 years. Individual and simultaneous phantom movements were predicted using myoelectric pattern recognition and were then used as input for VR and AR environments, as well as for a racing game. The sustained level of pain reported by the patient was gradually reduced to complete pain-free periods. The phantom posture initially reported as a strongly closed fist was gradually relaxed, interestingly resembling the neutral posture displayed by the virtual limb. The patient acquired the ability to freely move his phantom limb, and a telescopic effect was observed where the position of the phantom hand was restored to the anatomically correct distance. More importantly, the effect of the interventions was positively and noticeably perceived by the patient and his relatives. Despite the limitation of a single case study, the successful results of the proposed system in a patient for whom other medical and non-medical treatments have been ineffective justifies and motivates further investigation in a wider study. PMID:24616655

  15. Treatment of phantom limb pain (PLP) based on augmented reality and gaming controlled by myoelectric pattern recognition: a case study of a chronic PLP patient.

    PubMed

    Ortiz-Catalan, Max; Sander, Nichlas; Kristoffersen, Morten B; Håkansson, Bo; Brånemark, Rickard

    2014-01-01

    A variety of treatments have been historically used to alleviate phantom limb pain (PLP) with varying efficacy. Recently, virtual reality (VR) has been employed as a more sophisticated mirror therapy. Despite the advantages of VR over a conventional mirror, this approach has retained the use of the contralateral limb and is therefore restricted to unilateral amputees. Moreover, this strategy disregards the actual effort made by the patient to produce phantom motions. In this work, we investigate a treatment in which the virtual limb responds directly to myoelectric activity at the stump, while the illusion of a restored limb is enhanced through augmented reality (AR). Further, phantom motions are facilitated and encouraged through gaming. The proposed set of technologies was administered to a chronic PLP patient who has shown resistance to a variety of treatments (including mirror therapy) for 48 years. Individual and simultaneous phantom movements were predicted using myoelectric pattern recognition and were then used as input for VR and AR environments, as well as for a racing game. The sustained level of pain reported by the patient was gradually reduced to complete pain-free periods. The phantom posture initially reported as a strongly closed fist was gradually relaxed, interestingly resembling the neutral posture displayed by the virtual limb. The patient acquired the ability to freely move his phantom limb, and a telescopic effect was observed where the position of the phantom hand was restored to the anatomically correct distance. More importantly, the effect of the interventions was positively and noticeably perceived by the patient and his relatives. Despite the limitation of a single case study, the successful results of the proposed system in a patient for whom other medical and non-medical treatments have been ineffective justifies and motivates further investigation in a wider study.

  16. Bioinformatic analysis of a PLP-dependent enzyme superfamily suitable for biocatalytic applications.

    PubMed

    Steffen-Munsberg, Fabian; Vickers, Clare; Kohls, Hannes; Land, Henrik; Mallin, Hendrik; Nobili, Alberto; Skalden, Lilly; van den Bergh, Tom; Joosten, Henk-Jan; Berglund, Per; Höhne, Matthias; Bornscheuer, Uwe T

    2015-01-01

    In this review we analyse structure/sequence-function relationships for the superfamily of PLP-dependent enzymes with special emphasis on class III transaminases. Amine transaminases are highly important for applications in biocatalysis in the synthesis of chiral amines. In addition, other enzyme activities such as racemases or decarboxylases are also discussed. The substrate scope and the ability to accept chemically different types of substrates are shown to be reflected in conserved patterns of amino acids around the active site. These findings are condensed in a sequence-function matrix, which facilitates annotation and identification of biocatalytically relevant enzymes and protein engineering thereof.

  17. The Pseudomonas aeruginosa patatin-like protein PlpD is the archetype of a novel Type V secretion system.

    PubMed

    Salacha, Richard; Kovacić, Filip; Brochier-Armanet, Céline; Wilhelm, Susanne; Tommassen, Jan; Filloux, Alain; Voulhoux, Romé; Bleves, Sophie

    2010-06-01

    We discovered a novel secreted protein by Pseudomonas aeruginosa, PlpD, as a member of the bacterial lipolytic enzyme family of patatin-like proteins (PLPs). PlpD is synthesized as a single molecule consisting of a secreted domain fused to a transporter domain. The N-terminus of PlpD includes a classical signal peptide followed by the four PLP conserved blocks that account for its lipase activity. The C-terminus consists of a POTRA (polypeptide transport-associated) motif preceding a putative 16-stranded beta-barrel similar to those of TpsB transporters of Type Vb secretion system. We showed that the C-terminus remains inserted into the outer membrane while the patatin moiety is secreted. The association between a TpsB component and a passenger protein is a unique hybrid organization that we propose to classify as Type Vd. More than 200 PlpD orthologues exist among pathogenic and environmental bacteria, which suggests that bacteria secrete numerous PLPs using this newly defined mechanism.

  18. A novel PLP1 mutation associated with optic nerve enlargement in two siblings with Pelizaeus-Merzbacher disease: A new MRI finding.

    PubMed

    Pavlidou, Efterpi; Ramachandran, Vijaya; Govender, Veronica; Wilson, Clare; Das, Rini; Vlachou, Victoria; Pavlou, Evangelos; Saggar, Anand; Mankad, Kshitij; Kinali, Maria

    2017-03-01

    Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked disorder characterized by hypomyelination of the Central Nervous System due to mutations in the PLP1 gene. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement. To the best of our knowledge this is the first time that this novel mutation H133P of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients.

  19. Complex Genomic Rearrangements at the PLP1 Locus Include Triplication and Quadruplication

    PubMed Central

    Beck, Christine R.; Carvalho, Claudia M. B.; Banser, Linda; Gambin, Tomasz; Stubbolo, Danielle; Yuan, Bo; Sperle, Karen; McCahan, Suzanne M.; Henneke, Marco; Seeman, Pavel; Hobson, Grace M.; Lupski, James R.

    2015-01-01

    Inverted repeats (IRs) can facilitate structural variation as crucibles of genomic rearrangement. Complex duplication—inverted triplication—duplication (DUP-TRP/INV-DUP) rearrangements that contain breakpoint junctions within IRs have been recently associated with both MECP2 duplication syndrome (MIM#300260) and Pelizaeus-Merzbacher disease (PMD, MIM#312080). We investigated 17 unrelated PMD subjects with copy number gains at the PLP1 locus including triplication and quadruplication of specific genomic intervals—16/17 were found to have a DUP-TRP/INV-DUP rearrangement product. An IR distal to PLP1 facilitates DUP-TRP/INV-DUP formation as well as an inversion structural variation found frequently amongst normal individuals. We show that a homology—or homeology—driven replicative mechanism of DNA repair can apparently mediate template switches within stretches of microhomology. Moreover, we provide evidence that quadruplication and potentially higher order amplification of a genomic interval can occur in a manner consistent with rolling circle amplification as predicted by the microhomology-mediated break induced replication (MMBIR) model. PMID:25749076

  20. Use of DEAD-box polypeptide-4 (Ddx4) gene promoter-driven fluorescent reporter mice to identify mitotically active germ cells in post-natal mouse ovaries

    PubMed Central

    Park, Eun-Sil; Tilly, Jonathan L.

    2015-01-01

    Several laboratories have independently isolated mitotically active germ cells, termed female germline stem cells or oogonial stem cells (OSCs), from adult mouse ovaries. However, a recent study using Ddx4-Cre;Rosa26 reporter mice concluded that such germ cells do not exist. Given the disparity in conclusions drawn in this study compared with others, we felt it was important to re-assess the utility of Ddx4-Cre;Rosa26 reporter mice for identification of OSCs in adult mouse ovaries. Transgenic Ddx4-Cre mice were crossed with Rosa26tdTm/tdTm mice to drive restricted tomato red (tdTm) gene expression in cells in which the Ddx4 gene promoter has been activated. Crude dispersion of ovaries from recombined offspring generated cell fractions containing tdTm-positive immature oocytes, which are incapable of proliferation and thus probably represent the uncharacterized reporter-positive ovarian cells identified in the paper Zhang et al. (2012) as being mitotically inactive. Dispersed ovaries further subjected to fluorescence-activated cell sorting yielded a large population of non-germline tdTm-positive cells, indicative of promoter ‘leakiness’ in the Ddx4-Cre mouse line. Nonetheless, a small percentage of these tdTm-positive cells exhibited externalized (extracellular, ec) expression of Ddx4 protein (ecDdx4-positive), expressed markers of primitive germ cells but not of oocytes, and actively proliferated in culture, all of which are characteristic features of OSCs. Thus, crude dispersion of ovaries collected from Ddx4 gene promoter-driven reporter mice is not, by itself, a reliable approach to identify OSCs, whereas the same ovarian dispersates further subjected to cell sorting strategies yield purified OSCs that can be expanded in culture. PMID:25147160

  1. Use of DEAD-box polypeptide-4 (Ddx4) gene promoter-driven fluorescent reporter mice to identify mitotically active germ cells in post-natal mouse ovaries.

    PubMed

    Park, Eun-Sil; Tilly, Jonathan L

    2015-01-01

    Several laboratories have independently isolated mitotically active germ cells, termed female germline stem cells or oogonial stem cells (OSCs), from adult mouse ovaries. However, a recent study using Ddx4-Cre;Rosa26 reporter mice concluded that such germ cells do not exist. Given the disparity in conclusions drawn in this study compared with others, we felt it was important to re-assess the utility of Ddx4-Cre;Rosa26 reporter mice for identification of OSCs in adult mouse ovaries. Transgenic Ddx4-Cre mice were crossed with Rosa26(tdTm/tdTm) mice to drive restricted tomato red (tdTm) gene expression in cells in which the Ddx4 gene promoter has been activated. Crude dispersion of ovaries from recombined offspring generated cell fractions containing tdTm-positive immature oocytes, which are incapable of proliferation and thus probably represent the uncharacterized reporter-positive ovarian cells identified in the paper Zhang et al. (2012) as being mitotically inactive. Dispersed ovaries further subjected to fluorescence-activated cell sorting yielded a large population of non-germline tdTm-positive cells, indicative of promoter 'leakiness' in the Ddx4-Cre mouse line. Nonetheless, a small percentage of these tdTm-positive cells exhibited externalized (extracellular, ec) expression of Ddx4 protein (ecDdx4-positive), expressed markers of primitive germ cells but not of oocytes, and actively proliferated in culture, all of which are characteristic features of OSCs. Thus, crude dispersion of ovaries collected from Ddx4 gene promoter-driven reporter mice is not, by itself, a reliable approach to identify OSCs, whereas the same ovarian dispersates further subjected to cell sorting strategies yield purified OSCs that can be expanded in culture.

  2. LKTA and PlpE small fragments fusion protein protect against Mannheimia haemolytica challenge.

    PubMed

    Guzmán-Brambila, Carolina; Quintero-Fabián, Saray; González-Castillo, Celia; de Obeso-Fernández del Valle, Álvaro; Flores-Samaniego, Beatriz; de la Mora, Germán; Rojas-Mayorquín, Argelia E; Ortuño-Sahagún, Daniel

    2012-12-01

    Bovine respiratory disease (BRD) complex is a major cause of economic losses for the cattle backgrounding and feedlot industries. Mannheimia haemolytica is considered the most important pathogen associated with this disease. Vaccines against M. haemolytica have been prepared and used for many decades, but traditional bacterins have failed to demonstrate effective protection and their use has often exacerbated disease in vaccinated animals. Thus, the BRD complex continues to exert a strong adverse effect on the health and wellbeing of stocker and feeder cattle. Therefore, generation of recombinant proteins has been helpful in formulating enhanced vaccines against M. haemolytica, which could confer better protection against BRD. In the present study, we formulated a vaccine preparation enriched with recombinant small fragments of leukotoxin A (LKTA) and outer-membrane lipoprotein (PlpE) proteins, and demonstrated its ability to generate high antibody titers in rabbits and sheep, which protected against M. haemolytica bacterial challenge in mice.

  3. Enhanced method of magnetic powder alignment for production of PLP Nd-Fe-B magnets

    NASA Astrophysics Data System (ADS)

    Popov, A. G.; Golovnia, O. A.; Protasov, A. V.

    2017-04-01

    It is demonstrated how the high degree of powder alignment in PLP magnets can be achieved by loading the powder into a container placed in a magnetic field of moderate strength. The strip-cast alloy with a composition of 30.00 Nd, 1.95 Dy, 66.42 Fe, 0.99 B, 0.54 Co, 0.1 Ga (wt%) was subjected to hydrogen decrepitation and then milled in a vibratory mill in toluene to an average particle size of 2.9 μm determined by the FSSS method. The powder was compacted in the magnetic field of 0.2 - 1.2 T to the filling density 2.6 - 3.2×103 kg/m3. It is shown that loading the powder into a container placed in a magnetic field enhances the degree of powder alignment in sintered Nd-Fe-B magnets produced from non-pressed powder. At the filling density less than 3.2×103 kg/m3, the density of magnets is high but insufficient, because of the formation of magnetostatic chains of particles, which impedes the powder compaction. The simulation by the discrete-element method qualitatively proves that the magnetostatic interaction of the chains of particles that are formed in the course of loading in the magnetic field stimulates a decrease in the density of the sintered magnets and its non-uniform distribution over the sample. As a result of the optimization of the parameters of the alignment and compaction of the powder loaded in a magnetic field, PLP magnets with Br ≥1.34 T, Нc ≥950 kA/m, (BH)max ≥340 kJ/m3, and the degree of alignment exceeding 96% were produced.

  4. Myelin-reactive antibodies mediate the pathology of MBP-PLP fusion protein MP4-induced EAE.

    PubMed

    Kuerten, Stefanie; Pauly, Robert; Rottlaender, Andrea; Rodi, Michael; Gruppe, Traugott L; Addicks, Klaus; Tary-Lehmann, Magdalena; Lehmann, Paul V

    2011-07-01

    Experimental autoimmune encephalomyelitis (EAE) is frequently used for studies of multiple sclerosis (MS). Because in most EAE models T cells mediate the pathology in the absence of B cells/autoantibodies, the notion has evolved that also MS may be a primarily T cell-mediated disease. We have previously introduced MBP-PLP fusion protein (MP4)-induced EAE in C57BL/6 mice. Here we show that the disease in this model is antibody-dependent. Immunization of B cell-deficient mice did not induce EAE. When such B cell-deficient mice were, however, injected with MBP/PLP-specific antibodies in addition to the immunization with MP4, they developed disease of a severity and course that was similar to the wild-type mice. The deposition of antibodies in demyelinated lesions provided further evidence for the contribution of MBP/PLP-specific antibodies to CNS lesion formation. Based upon these data we suggest a two-stage model for the involvement of MBP/PLP-specific antibodies in autoimmune CNS pathology.

  5. Mechanism of substrate recognition and PLP-induced conformational changes in LL-diaminopimelate aminotransferase from Arabidopsis thaliana.

    PubMed

    Watanabe, Nobuhiko; Clay, Matthew D; van Belkum, Marco J; Cherney, Maia M; Vederas, John C; James, Michael N G

    2008-12-31

    LL-Diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal phosphate (PLP)-dependent enzyme in the lysine biosynthetic pathways of plants and Chlamydia, is a potential target for the development of herbicides or antibiotics. This homodimeric enzyme converts L-tetrahydrodipicolinic acid (THDP) directly to LL-DAP using L-glutamate as the source of the amino group. Earlier, we described the 3D structures of native and malate-bound LL-DAP-AT from Arabidopsis thaliana (AtDAP-AT). Seven additional crystal structures of AtDAP-AT and its variants are reported here as part of an investigation into the mechanism of substrate recognition and catalysis. Two structures are of AtDAP-AT with reduced external aldimine analogues: N-(5'-phosphopyridoxyl)-L-glutamate (PLP-Glu) and N-(5'-phosphopyridoxyl)- LL-Diaminopimelate (PLP-DAP) bound in the active site. Surprisingly, they reveal that both L-glutamate and LL-DAP are recognized in a very similar fashion by the same sets of amino acid residues; both molecules adopt twisted V-shaped conformations. With both substrates, the alpha-carboxylates are bound in a salt bridge with Arg404, whereas the distal carboxylates are recognized via hydrogen bonds to the well-conserved side chains of Tyr37, Tyr125 and Lys129. The distal C(epsilon) amino group of LL-DAP is specifically recognized by several non-covalent interactions with residues from the other subunit (Asn309*, Tyr94*, Gly95*, and Glu97* (Amino acid designators followed by an asterisk (*) indicate that the residues originate in the other subunit of the dimer)) and by three bound water molecules. Two catalytically inactive variants of AtDAP-AT were created via site-directed mutagenesis of the active site lysine (K270N and K270Q). The structures of these variants permitted the observation of the unreduced external aldimines of PLP with L-glutamate and with LL-DAP in the active site, and revealed differences in the torsion angle about the PLP-substrate bond. Lastly, an apo

  6. Mechanism of Substrate Recognition And PLP-Induced Conformational Changes in II-Diaminopimelate Aminotransferase From Arabidopsis Thaliana

    SciTech Connect

    Watanabe, N.; Clay, M.D.; Belkum, M.J.van; Cherney, M.M.; Vederas, J.C.; James, M.N.G.

    2009-05-26

    LL-Diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal phosphate (PLP)-dependent enzyme in the lysine biosynthetic pathways of plants and Chlamydia, is a potential target for the development of herbicides or antibiotics. This homodimeric enzyme converts L-tetrahydrodipicolinic acid (THDP) directly to LL-DAP using L-glutamate as the source of the amino group. Earlier, we described the 3D structures of native and malate-bound LL-DAP-AT from Arabidopsis thaliana (AtDAP-AT). Seven additional crystal structures of AtDAP-AT and its variants are reported here as part of an investigation into the mechanism of substrate recognition and catalysis. Two structures are of AtDAP-AT with reduced external aldimine analogues: N-(5'-phosphopyridoxyl)-L-glutamate (PLP-Glu) and N-(5'-phosphopyridoxyl)- LL-Diaminopimelate (PLP-DAP) bound in the active site. Surprisingly, they reveal that both L-glutamate and LL-DAP are recognized in a very similar fashion by the same sets of amino acid residues; both molecules adopt twisted V-shaped conformations. With both substrates, the {alpha}-carboxylates are bound in a salt bridge with Arg404, whereas the distal carboxylates are recognized via hydrogen bonds to the well-conserved side chains of Tyr37, Tyr125 and Lys129. The distal C{sup {var_epsilon}} amino group of LL-DAP is specifically recognized by several non-covalent interactions with residues from the other subunit (Asn309*, Tyr94*, Gly95*, and Glu97* (Amino acid designators followed by an asterisk (*) indicate that the residues originate in the other subunit of the dimer)) and by three bound water molecules. Two catalytically inactive variants of AtDAP-AT were created via site-directed mutagenesis of the active site lysine (K270N and K270Q). The structures of these variants permitted the observation of the unreduced external aldimines of PLP with L-glutamate and with LL-DAP in the active site, and revealed differences in the torsion angle about the PLP-substrate bond. Lastly, an apo

  7. PLP-dependent enzymes as entry and exit gates of sphingolipid metabolism

    PubMed Central

    Bourquin, Florence; Capitani, Guido; Grütter, Markus Gerhard

    2011-01-01

    Sphingolipids are membrane constituents as well as signaling molecules involved in many essential cellular processes. Serine palmitoyltransferase (SPT) and sphingosine-1-phosphate lyase (SPL), both PLP (pyridoxal 5′-phosphate)-dependent enzymes, function as entry and exit gates of the sphingolipid metabolism. SPT catalyzes the condensation of serine and a fatty acid into 3-keto-dihydrosphingosine, whereas SPL degrades sphingosine-1-phosphate (S1P) into phosphoethanolamine and a long-chain aldehyde. The recently solved X-ray structures of prokaryotic homologs of SPT and SPL combined with functional studies provide insight into the structure–function relationship of the two enzymes. Despite carrying out different reactions, the two enzymes reveal striking similarities in the overall fold, topology, and residues crucial for activity. Unlike their eukaryotic counterparts, bacterial SPT and SPL lack a transmembrane helix, making them targets of choice for biochemical characterization because the use of detergents can be avoided. Both human enzymes are linked to severe diseases or disorders and might therefore serve as targets for the development of therapeutics aiming at the modulation of their activity. This review gives an overview of the sphingolipid metabolism and of the available biochemical studies of prokaryotic SPT and SPL, and discusses the major similarities and differences to the corresponding eukaryotic enzymes. PMID:21710479

  8. Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

    PubMed

    Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

    2017-03-01

    In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases.

  9. Role of the pyridine nitrogen in pyridoxal 5'-phosphate catalysis: activity of three classes of PLP enzymes reconstituted with deazapyridoxal 5'-phosphate.

    PubMed

    Griswold, Wait R; Toney, Michael D

    2011-09-21

    Pyridoxal 5'-phosphate (PLP; vitamin B(6))-catalyzed reactions have been well studied, both on enzymes and in solution, due to the variety of important reactions this cofactor catalyzes in nitrogen metabolism. Three functional groups are central to PLP catalysis: the C4' aldehyde, the O3' phenol, and the N1 pyridine nitrogen. In the literature, the pyridine nitrogen has traditionally been assumed to be protonated in enzyme active sites, with the protonated pyridine ring providing resonance stabilization of carbanionic intermediates. This assumption is certainly correct for some PLP enzymes, but the structures of other active sites are incompatible with protonation of N1, and, consequently, these enzymes are expected to use PLP in the N1-unprotonated form. For example, aspartate aminotransferase protonates the pyridine nitrogen for catalysis of transamination, while both alanine racemase and O-acetylserine sulfhydrylase are expected to maintain N1 in the unprotonated, formally neutral state for catalysis of racemization and β-elimination. Herein, kinetic results for these three enzymes reconstituted with 1-deazapyridoxal 5'-phosphate, an isosteric analogue of PLP lacking the pyridine nitrogen, are compared to those for the PLP enzyme forms. They demonstrate that the pyridine nitrogen is vital to the 1,3-prototropic shift central to transamination, but not to reactions catalyzed by alanine racemase or O-acetylserine sulfhydrylase. Not all PLP enzymes require the electrophilicity of a protonated pyridine ring to enable formation of carbanionic intermediates. It is proposed that modulation of cofactor electrophilicity plays a central role in controlling reaction specificity in PLP enzymes.

  10. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  11. Homology-based molecular modelling of PLP-dependent histidine decarboxylase from Mmorganella morganii.

    PubMed

    Tahanejad, F S; Naderi-Manesh, H; Habibinejad, B; Mahmoudian, M

    2000-06-01

    The 3-D structural information is a prerequisite for a rational ligand design. In the absence of experimental data, model building on the basis of a known 3-D structure of a homologous protein is at present the only reliable method to obtain structural information. A homology model building study of the pyridoxal 5'-phosphate (PLP)-dependent histidine decarboxylase from Morganella morganii (HDC-MM) has been carried out based on the crystal structure of the aspartate aminotransferase from Escherichia coli (AAT-EC). The primary sequences of AAT-EC and HDC-MM were aligned by automated alignment procedure. A 3-D model of HDC-MM was constructed by copying the coordinates of the residues from the crystal structure of AAT-EC into the corresponding residues in HDC-MM. After energy-minimization of the resulting 3-D model of HDC-MM, possible active site residues were identified by fitting the substrate (l-histidine) into the proposed active-site. In our model, several residues, which have an important role in the AAT-EC active-site, are located in positions spatially identical to those in AAT-EC structure. The back-bone of the modelled active site pocket is constructed by residues; Gly-92, Gly-93, Thr-93, Ser-115, Asp-200, Ala-202, Ser-229 and Lys-232 together with residues Asn-8, His-119, Thr-171, His-198, Leu-203, His-231, Ser-236 and Ile-238. In the ligand binding site, it appears that the HDC-MM model will position l-histidine (substrate) in the area consisting of the residues; Glu-29, Ser-30, Leu-38, His-231 and Lys-232. The nitrogen atom of the imidazole ring (N2) of the substrate is predicted to interact with the carboxylate group of Ser-30. The alpha-carboxylate of histidine points toward the Lys-232 to have electrostatic interaction with its side chain nitrogen atom (N(Z)). In conclusion, this combination of sequence and 3-D structural homology between AAT-EC and HDC-MM model could provide insight in assigning the probable active site residues.

  12. Haploid Genetic Screens Identify an Essential Role for PLP2 in the Downregulation of Novel Plasma Membrane Targets by Viral E3 Ubiquitin Ligases

    PubMed Central

    Timms, Richard T.; Duncan, Lidia M.; Tchasovnikarova, Iva A.; Antrobus, Robin; Smith, Duncan L.; Dougan, Gordon; Weekes, Michael P.; Lehner, Paul J.

    2013-01-01

    The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2), a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system. PMID:24278019

  13. Distinct Parameters in the EEG of the PLP α-SYN Mouse Model for Multiple System Atrophy Reinforce Face Validity

    PubMed Central

    Härtner, Lorenz; Keil, Tobias W. M.; Kreuzer, Matthias; Fritz, Eva Maria; Wenning, Gregor K.; Stefanova, Nadia; Fenzl, Thomas

    2017-01-01

    Multiple system atrophy (MSA) is a neurodegenerative movement disorder characterized by parkinsonian symptoms and cerebellar symptoms. Sleep disturbances also play a crucial role in MSA. One of the most convincing animal models in MSA research is the PLP α-SYN model, but to date no studies on sleep disturbances in this mouse model, frequently found in MSA patients are available. We identified spectral shifts within the EEG of the model, strikingly resembling results of clinical studies. We also characterized muscle activity during REM sleep, which is one of the key symptoms in REM sleep behavioral disorder. Spectral shifts and REM sleep-linked muscle activity were age dependent, supporting Face Validity of the PLP α-SYN model. We also strongly suggest our findings to be critically evaluated for Predictive Validity in future studies. Currently, research on MSA lacks potential compounds attenuating or curing MSA. Future drugs must prove its potential in animal models, for this our study provides potential biomarkers. PMID:28119583

  14. A PLP-dependent polyketide chain releasing mechanism in the biosynthesis of mycotoxin fumonisins in Fusarium verticillioides.

    PubMed

    Gerber, Ryan; Lou, Lili; Du, Liangcheng

    2009-03-11

    Fumonisins are polyketide-derived mycotoxins produced by several plant pathogenic fungi. The toxins cause several fatal diseases in domestic animals and are associated with esophageal cancer and neural tube defects in humans. Fumonisins contain a highly reduced, acyclic 18-carbon chain, which is synthesized by an iterative polyketide synthase (PKS). This PKS does not contain a thioesterase or cyclase domain that is found in other PKSs for the release of the covalently linked polyketide chain. In this study, we expressed the acyl carrier protein (ACP) of FUM1 and in vitro loaded acyl chains to the ACP from acyl-CoA using a promiscuous 4'-phosphopantetheinyl transferase. We then expressed FUM8, which is homologous to 2-oxoamine synthase genes, in yeast and showed that the enzyme is able to offload the acyl chains from ACP. Products resulted from the decarboxylative condensation between l-alanine and acyl-S-ACP were detected by GC-MS. The enzyme activity was dependent on pyridoxal 5'-phosphate (PLP), and C18-S-ACP was the preferred substrate. The results revealed a novel polyketide chain-releasing mechanism, in which a PLP-dependent enzyme catalyzes the termination and offloading of the polyketide chain as well as the introduction of a new carbon-carbon bond and an amino group to the chain. The mechanism is fundamentally different from the thioesterase/cyclase-catalyzed polyketide chain release found in bacterial and other fungal polyketide biosyntheses.

  15. Postnatal growth of genioglossal motoneurons.

    PubMed

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

    1989-01-01

    The postnatal growth of kitten genioglossal motoneurons were examined in six different age groups (newborn, 2, 4, 8, and 12 weeks and adult) using the technique of retrograde transport of horseradish peroxidase (HRP). The cell bodies of 100-150 motoneurons in each age group were analyzed in a transverse plane of section using standard techniques. Somatic genioglossal motoneuron growth occurred primarily along the major axis, which increased from 25.2 microns to 41.3 microns between birth and 8 weeks of postnatal age, after which time there was no further increase in either major or minor dimension of the cell body. The form factor decreased from 0.94 to 0.80 from birth to adulthood indicating an increased eccentricity of the cell body. The number of primary dendrites visible with this technique remained constant throughout the postnatal period. Calculated somal surface area increased in a linear fashion from birth through 8 weeks of postnatal life. There was no further increase in surface area beyond this age. The rate of increase in somal surface area with age was significantly different from both the rate of increase of animal weight and animal surface area with age. The correlations between the demonstrated immature genioglossal morphology and its cellular electrophysiology or integrated respiratory function remain unknown. The recent demonstration of decreased activation of the genioglossus muscle following airway occlusion in premature infants with apnea suggests that the relationships between developing genioglossal motoneuron structure and function warrant further investigation.

  16. Postnatal effects of prenatal insult

    SciTech Connect

    Johnson, E.M.; Newman, L.M.; Schmidt, R.R.

    1988-03-01

    Exogenous agents may perturb development during the embryonic period and adversely affect the formation of organs. However, adverse effects on development are not limited to the embryonic period nor are the manifestations restricted solely to outright gross structural malformation, but may instead be expressed as a decrement or abberration of postnatal function. Susceptibility to altered development may extend well into the postnatal period. Studies of functional parameters in several organ systems have demonstrated the broad-based susceptibility, subtlety of expression and potential of long-lasting effects of altered development assessed by physiologic assays. Adverse effects on functional development, whether in the CNS, reproductive, gastrointestinal, genitourinary, respiratory, or immune systems, etc., merit continuing investigation. From the viewpoint of risk estimation and hazard detection, evaluations of postnatal functional parameters may be relevant for several reasons. First, such parameters may serve as low-dose triggers. Second, they may be useful as a focal point for epidemiological studies. Finally, a more thorough understanding of the degree and magnitude of such postnatal functional deficits is needed since an adverse maternal effect may be transient, considered acceptable, or unperceived, but the effect on the conceptus may be permanent and severe. The immune and respiratory systems are discussed as two examples of how subtle and protean adverse effects on functional development may be.

  17. The Effect of the Disease-Causing R266K Mutation on the Heme and PLP Environments of Human Cystathionine β-Synthase

    PubMed Central

    Smith, Aaron T.; Su, Yang; Stevens, Daniel J.; Majtan, Tomas; Kraus, Jan P.; Burstyn, Judith N.

    2012-01-01

    Cystathionine β-synthase (CBS) is an essential PLP-dependent enzyme of the transsulfuration pathway that condenses serine with homocysteine to form cystathionine; intriguingly, human CBS also contains a heme b cofactor of unknown function. Herein we describe the enzymatic and spectroscopic properties of a disease-associated R266K hCBS variant, which has an altered hydrogen-bonding environment. The R266K hCBS contains a low-spin, six-coordinate Fe(III) heme bearing a His/Cys ligation motif, like that of WT hCBS; however, there is a geometric distortion that exists at the R266K heme. Using rR spectroscopy, we show that the Fe(III)-Cys(thiolate) bond is longer and weaker in R266K, as evidenced by an 8 cm−1 downshift in the ν(Fe-S) resonance. Presence of this longer and weaker Fe(III)-Cys(thiolate) is correlated with alteration of the fluorescence spectrum of the active PLP ketoenamine tautomer. Activity data demonstrate that, relative to WT, the R266K variant is more impaired in the alternative cysteine-synthesis reaction than in the canonical cystathionine-synthesis reaction. This diminished cysteine synthesis activity and a greater sensitivity to exogenous PLP correlates with the change in PLP environment. Fe-S(Cys) bond weakening causes a nearly 300-fold increase in the rate of ligand switching upon reduction of the R266K heme. Combined, these data demonstrate cross talk between the heme and PLP active sites, consistent with previous proposals, revealing that alteration of the Arg266-Cys52 interaction affects PLP-dependent activity and dramatically destabilizes the ferrous thiolate-ligated heme complex, underscoring the importance of this hydrogen-bonding residue pair. PMID:22738154

  18. Prevalence of Anaemia among Postnatal Mothers in Coastal Karnataka

    PubMed Central

    Bhagwan, Darshan; Kumar, Ashwini; Kamath, Asha

    2016-01-01

    Introduction Postpartum is the most neglected period in reproductive cycle of woman. Prevalence of anaemia in developing countries ranges from 50-95%. Aim To estimate the prevalence of anaemia among postnatal mothers. Setting and design A community based cross-sectional study among recently delivered mothers residing in field practice area of Department of Community Medicine, Kasturba Medical College, Manipal, India. Materials and Methods The study sample included 401 respondents who were selected using stratified random sampling with proportionate allocation from all rural health centres. Data was collected by personal interviews followed by haemoglobin estimation by indirect cyanomethaemoglobin method. Results The prevalence of postnatal anaemia was 26.5% (Anaemia = Hb<12gm/dl). There were no cases of severe anaemia. Postnatal anaemia was predominantly seen in mothers of age < 20 years and half of the mothers with inter-pregnancy intervals less than two years were found to be anaemic. Illiteracy was identified as a significant variable (OR=11.23, 95% CI = 1.90-65.08) for postpartum anaemia. Conclusion The prevalence of anaemia was significantly lower in the present study; however sustained efforts have to be made to further lower the prevalence of postnatal anaemia in order to promote the health and well-being of women. PMID:26894096

  19. Postnatal blues: a risk factor for postnatal depression.

    PubMed

    Henshaw, C; Foreman, D; Cox, J

    2004-01-01

    Postnatal blues have been regarded as brief, benign and without clinical significance. However, several studies have proposed a link between blues and subsequent depression but have methodological problems. We report a prospective, controlled study of postpartum women with severe blues which uses systematically devised and validated instruments for that purpose which tests the hypothesis that severe blues increases the risk of depression in the six months following childbirth. 206 first-time mothers were recruited in late pregnancy. Blues status was defined using the Blues Questionnaire and those with severe blues and their controls who had no blues (matched for age, marital status and social class) were followed for 6 months with postal Edinburgh Postnatal Depression Scale. RDC diagnoses were made following SADS-L interview at the end of the protocol. Backwards stepwise Cox regression analysis found severe blues and past history of depression to be independent predictors each raising the risk by almost 3 times. Depression in those with severe blues onset sooner after delivery and lasted longer. The difference was largely accounted for by major depression. Severe postpartum blues are identified as an independent risk factor for subsequent postpartum depression. Screening and intervention programs could be devised.

  20. Generic HPLC platform for automated enzyme reaction monitoring: Advancing the assay toolbox for transaminases and other PLP-dependent enzymes.

    PubMed

    Börner, Tim; Grey, Carl; Adlercreutz, Patrick

    2016-08-01

    Methods for rapid and direct quantification of enzyme kinetics independent of the substrate stand in high demand for both fundamental research and bioprocess development. This study addresses the need for a generic method by developing an automated, standardizable HPLC platform monitoring reaction progress in near real-time. The method was applied to amine transaminase (ATA) catalyzed reactions intensifying process development for chiral amine synthesis. Autosampler-assisted pipetting facilitates integrated mixing and sampling under controlled temperature. Crude enzyme formulations in high and low substrate concentrations can be employed. Sequential, small (1 µL) sample injections and immediate detection after separation permits fast reaction monitoring with excellent sensitivity, accuracy and reproducibility. Due to its modular design, different chromatographic techniques, e.g. reverse phase and size exclusion chromatography (SEC) can be employed. A novel assay for pyridoxal 5'-phosphate-dependent enzymes is presented using SEC for direct monitoring of enzyme-bound and free reaction intermediates. Time-resolved changes of the different cofactor states, e.g. pyridoxal 5'-phosphate, pyridoxamine 5'-phosphate and the internal aldimine were traced in both half reactions. The combination of the automated HPLC platform with SEC offers a method for substrate-independent screening, which renders a missing piece in the assay and screening toolbox for ATAs and other PLP-dependent enzymes.

  1. The crystal structure of D-threonine aldolase from Alcaligenes xylosoxidans provides insight into a metal ion assisted PLP-dependent mechanism.

    PubMed

    Uhl, Michael K; Oberdorfer, Gustav; Steinkellner, Georg; Riegler-Berket, Lina; Mink, Daniel; van Assema, Friso; Schürmann, Martin; Gruber, Karl

    2015-01-01

    Threonine aldolases catalyze the pyridoxal phosphate (PLP) dependent cleavage of threonine into glycine and acetaldehyde and play a major role in the degradation of this amino acid. In nature, L- as well as D-specific enzymes have been identified, but the exact physiological function of D-threonine aldolases (DTAs) is still largely unknown. Both types of enantio-complementary enzymes have a considerable potential in biocatalysis for the stereospecific synthesis of various β-hydroxy amino acids, which are valuable building blocks for the production of pharmaceuticals. While several structures of L-threonine aldolases (LTAs) have already been determined, no structure of a DTA is available to date. Here, we report on the determination of the crystal structure of the DTA from Alcaligenes xylosoxidans (AxDTA) at 1.5 Å resolution. Our results underline the close relationship of DTAs and alanine racemases and allow the identification of a metal binding site close to the PLP-cofactor in the active site of the enzyme which is consistent with the previous observation that divalent cations are essential for DTA activity. Modeling of AxDTA substrate complexes provides a rationale for this metal dependence and indicates that binding of the β-hydroxy group of the substrate to the metal ion very likely activates this group and facilitates its deprotonation by His193. An equivalent involvement of a metal ion has been implicated in the mechanism of a serine dehydratase, which harbors a metal ion binding site in the vicinity of the PLP cofactor at the same position as in DTA. The structure of AxDTA is completely different to available structures of LTAs. The enantio-complementarity of DTAs and LTAs can be explained by an approximate mirror symmetry of crucial active site residues relative to the PLP-cofactor.

  2. Family dynamics and postnatal depression.

    PubMed

    Tammentie, T; Tarkka, M-T; Astedt-Kurki, P; Paavilainen, E; Laippala, P

    2004-04-01

    Research has shown that postnatal depression (PND) affects 10-15% of mothers in Western societies. PND is not easily identified and therefore it often remains undetected. Untreated depression has a detrimental effect on the mother and child and the entire family. The purpose of this study was to ascertain the state of family dynamics after delivery and whether the mother's PND was associated with family dynamics. The study used a survey covering the catchment area of one Finnish university hospital. Both primi- and multiparas took part and data were collected using the Edinburgh Postnatal Depression Scale (EPDS) for mothers and the Family Dynamics Measure II (FDM II) for both mothers and fathers. The data were analysed using SPSS statistical programme and frequency and percentage distributions, means and standard deviations were examined. Correlations were analysed using Spearman's correlation coefficients. The significance of any differences between mothers' and fathers' scores was determined with a paired t-test. Of the families participating in the study (373 mothers and 314 partners), 13% of the mothers suffered from PND symptoms (EPDS score of 13 or more). As a whole, family dynamics in the families participating in the study were reported to be rather good. However, mothers having depressive symptoms reported more negative family dynamics compared with other families. With the exception of individuation, mothers having depressive symptoms reported more negative family dynamics than their partners. With the exception of role reciprocity, non-depressed mothers reported more positive family dynamics than their partners. Knowledge of the association of mothers' PND with family dynamics could help to develop nursing care at maternity and child welfare clinics and maternity hospitals. Depressed mothers and their families need support to be able to make family dynamics as good as possible.

  3. Differential patterns of spinal cord pathology induced by MP4, MOG peptide 35-55, and PLP peptide 178-191 in C57BL/6 mice.

    PubMed

    Kuerten, Stefanie; Gruppe, Traugott L; Laurentius, Laura-Maria; Kirch, Christiane; Tary-Lehmann, Magdalena; Lehmann, Paul V; Addicks, Klaus

    2011-06-01

    In this study we demonstrate that experimental autoimmune encephalomyelitis (EAE) induced by the MBP-PLP fusion protein MP4, MOG peptide 35-55, or PLP peptide 178-191 in C57BL/6 mice, respectively, displays distinct features of CNS pathology. Major differences between the three models resided in (i) the region-/tract-specificity and disseminated nature of spinal cord degeneration, (ii) the extent and kinetics of demyelination, and (iii) the involvement of motoneurons in the disease. In contrast, axonal damage was present in all models and to a similar extent, proposing this feature as a possible morphological correlate for the comparable chronic clinical course of the disease induced by the three antigens. The data suggest that the antigen targeted in autoimmune encephalomyelitis is crucial to the induction of differential histopathological disease manifestations. The use of MP4-, MOG:35-55-, and PLP:178-191-induced EAE on the C57BL/6 background can be a valuable tool when it comes to reproducing and studying the structural-morphological diversity of multiple sclerosis.

  4. The number of cells expressing the myelin-supporting oligodendrocyte marker PLP-exon 3b remains unchanged in Wallerian degeneration.

    PubMed

    Li, G; Blakemore, W F

    2004-08-01

    Following spinal cord trauma there is controversy as to whether myelin-supporting oligodendrocytes at a distance from areas of spinal cord damage undergo apoptosis. To examine the response of oligodendrocytes to axon degeneration, we counted the number of oligodendrocytes and oligodendrocyte precursors in the dorsal funiculi during the course of Wallerian degeneration. Axons were disrupted at T13 and the number of labelled cells in the dorsal funiculi counted at T12, 4 days and 2, 4, and 8 weeks after injury using riboprobes to exon-3b of the PLP gene whose expression is considered to restricted to myelin-supporting oligodendrocytes, PDGFRalpha which is regarded as a marker of oligodendrocyte precursors, and MOG a marker previously used to identify myelin-supporting oligodendrocytes. We found that the number of PLP-exon-3b labelled cells remained constant during the course of Wallerian degeneration while the number of cells labelled with the riboprobes to PDGFRalpha and MOG increased. Significantly the number of MOG-positive cells was increased at times when the number of PDGFRalpha labelled cells was highest. The number of PDGFRalpha labelled cells decreased with time while the number PLP-exon-3b labelled cells remained constant. It is therefore possible that the apoptotic oligodendrocytes identified in previous studies could represent degenerating oligodendrocyte precursors or their progeny rather than degenerating myelin-supporting oligodendrocytes.

  5. Antisense oligodeoxynucleotides targeted to MAG mRNA profoundly alter BP and PLP mRNA expression in differentiating oligodendrocytes: a caution.

    PubMed

    Laszkiewicz, I; Wiggins, R C; Konat, G W

    1999-09-01

    The applicability of antisense technology to suppress the expression of myelin associated glycoprotein (MAG) in cultured oligodendrocytes was evaluated. Differentiating oligodendrocyte precursor cells obtained by the shake-off method were exposed to nine unmodified antisense oligodeoxynucleotides (ODNs) targeted to the first seven exons of MAG mRNA. After four days, steady-state levels of MAG, proteolipid protein (PLP) and basic protein (BP) mRNAs were determined by Northern blot analysis. Only ODN annealing to 599-618 nt of the MAG mRNA (the junction of exon 5 and 6) resulted in a significant, 75% decrease in the MAG mRNA level. Unexpectedly, six other anti-MAG ODNs which had no significant effect on the MAG message, greatly increased the level of BP mRNA. The highest upregulation of approximately 12 fold was observed with ODN annealing to 139-168 nt (junction of exon 3 and 4). On the other hand, the 997-1016 ODN decreased the levels of BP and PLP messages by 70-80%. The 599-618 ODN also decreased the PLP mRNA by 85%. The results demonstrate that antisense ODNs targeted to one gene may profoundly alter the expression of other genes, and hence, complicate functional analysis of the targeted protein.

  6. [BREASTFEEDING AND FORMATION OF POSTNATAL ANXIETY].

    PubMed

    Klymenko, V A; Lupaltsova, O S

    2015-01-01

    This article has been performed the investigation of psychological characteristics in mothers with the breastfeeding, the mixed feeding, the artificial feeding. There has been identified factors of the unfavourable prognosis for the postnatal anxiety.

  7. Cholinergic circuit control of postnatal neurogenesis

    PubMed Central

    Asrican, Brent; Paez-Gonzalez, Patricia; Erb, Joshua; Kuo, Chay T.

    2016-01-01

    abstract New neuron addition via continued neurogenesis in the postnatal/adult mammalian brain presents a distinct form of nervous system plasticity. During embryonic development, precise temporal and spatial patterns of neurogenesis are necessary to create the nervous system architecture. Similar between embryonic and postnatal stages, neurogenic proliferation is regulated by neural stem cell (NSC)-intrinsic mechanisms layered upon cues from their local microenvironmental niche. Following developmental assembly, it remains relatively unclear what may be the key driving forces that sustain continued production of neurons in the postnatal/adult brain. Recent experimental evidence suggests that patterned activity from specific neural circuits can also directly govern postnatal/adult neurogenesis. Here, we review experimental findings that revealed cholinergic modulation, and how patterns of neuronal activity and acetylcholine release may differentially or synergistically activate downstream signaling in NSCs. Higher-order excitatory and inhibitory inputs regulating cholinergic neuron firing, and their implications in neurogenesis control are also considered. PMID:27468423

  8. Postnatal Loss of Hap1 Reduces Hippocampal Neurogenesis and Causes Adult Depressive-Like Behavior in Mice

    PubMed Central

    Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

    2015-01-01

    Depression is a serious mental disorder that affects a person’s mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression. PMID:25875952

  9. Congenital lung lesions: Postnatal management and outcome.

    PubMed

    Parikh, Dakshesh H; Rasiah, Shree Vishna

    2015-08-01

    Antenatal diagnosis of lung lesion has become more accurate resulting in dilemma and controversies of its antenatal and postnatal management. Majority of antenatally diagnosed congenital lung lesions are asymptomatic in the neonatal age group. Large lung lesions cause respiratory compromise and inevitably require urgent investigations and surgery. The congenital lung lesion presenting with hydrops requires careful postnatal management of lung hypoplasia and persistent pulmonary hypertension. Preoperative stabilization with gentle ventilation with permissive hypercapnia and delayed surgery similar to congenital diaphragmatic hernia management has been shown to result in good outcome. The diagnostic investigations and surgical management of the asymptomatic lung lesions remain controversial. Postnatal management and outcome of congenital cystic lung lesions are discussed.

  10. Epigenetic Upregulation of Corticotrophin-Releasing Hormone Mediates Postnatal Maternal Separation-Induced Memory Deficiency

    PubMed Central

    Wang, Aiyun; Nie, Wenying; Li, Haixia; Hou, Yuhua; Yu, Zhen; Fan, Qing; Sun, Ruopeng

    2014-01-01

    Accumulating evidences demonstrated that early postnatal maternal separation induced remarkable social and memory defects in the adult rodents. Early-life stress induced long-lasting functional adaptation of neuroendocrine hypothalamic-pituitary-adrenal axis, including neuropeptide corticotrophin-releasing hormone (CRH) in the brain. In the present study, a significantly increased hippocampal CRH was observed in the adult rats with postnatal maternal separation, and blockade of CRHR1 signaling significantly attenuated the hippocampal synaptic dysfunction and memory defects in the modeled rats. Postnatal maternal separation enduringly increased histone H3 acetylation and decreased cytosine methylation in Crh promoter region, resulting from the functional adaptation of several transcriptional factors, in the hippocampal CA1 of the modeled rats. Enriched environment reversed the epigenetic upregulation of CRH, and ameliorated the hippocampal synaptic dysfunction and memory defects in the adult rats with postnatal maternal separation. This study provided novel insights into the epigenetic mechanism underlying postnatal maternal separation-induced memory deficiency, and suggested environment enrichment as a potential approach for the treatment of this disorder. PMID:24718660

  11. Nociceptin and meiosis during spermatogenesis in postnatal testes.

    PubMed

    Eto, Ko

    2015-01-01

    Phosphorylated Rec8, a key component of cohesin, mediates the association and disassociation, "dynamics," of chromosomes occurring in synaptonemal complex formation, crossover recombination, and sister chromatid cohesion during meiosis in germ cells. Yet, the extrinsic factors triggering meiotic chromosome dynamics remained unclear. In postnatal testes, follicle-stimulating hormone (FSH) acts directly on somatic Sertoli cells to activate gene expression via an intracellular signaling pathway composed of cAMP, cAMP-dependent protein kinase (PKA), and cAMP-response element-binding protein (CREB), and promotes germ cell development and spermatogenesis indirectly. Yet, the paracrine factors mediating the FSH effects to germ cells remained elusive. We have shown that nociceptin, known as a neuropeptide, is upregulated by FSH signaling through cAMP/PKA/CREB pathway in Sertoli cells of postnatal murine testes. Chromatin immunoprecipitation from Sertoli cells demonstrated that CREB phosphorylated at Ser133 associates with prepronociceptin gene encoding nociceptin. Analyses with Sertoli cells and testes revealed that both prepronociceptin mRNA and the nociceptin peptide are induced after FSH signaling is activated. In addition, the nociceptin peptide is induced in testes after 9 days post partum following FSH surge. Thus, our findings may identify nociceptin as a novel paracrine mediator of the FSH effects in the regulation of spermatogenesis; however, very little has known about the functional role of nociceptin in spermatogenesis. We have shown that nociceptin induces Rec8 phosphorylation, triggering chromosome dynamics, during meiosis in spermatocytes of postnatal murine testes. The nociceptin receptor Oprl-1 is exclusively expressed in the plasma membrane of testicular germ cells, mostly spermatocytes. Treatment of testes with nociceptin resulted in a rapid phosphorylation of Rec8. Injection of nociceptin into mice stimulated Rec8 phosphorylation and meiotic chromosome

  12. 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.

  13. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    PubMed Central

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  14. Involvement of {gamma}-secretase in postnatal angiogenesis

    SciTech Connect

    Hayashi, Hiroki; Nakagami, Hironori Takami, Yoichi; Sato, Naoyuki; Saito, Yukihiro; Nishikawa, Tomoyuki; Mori, Masaki; Koriyama, Hiroshi; Tamai, Katsuto; Morishita, Ryuichi; Kaneda, Yasufumi

    2007-11-23

    {gamma}-Secretase cleaves the transmembrane domains of several integral membrane proteins involved in vasculogenesis. Here, we investigated the role of {gamma}-secretase in the regulation of postnatal angiogenesis using {gamma}-secretase inhibitors (GSI). In endothelial cell (EC), {gamma}-secretase activity was up-regulated under hypoxia or the treatment of vascular endothelial growth factor (VEGF). The treatment of GSI significantly attenuated growth factor-induced EC proliferation and migration as well as c-fos promoter activity in a dose-dependent manner. In vascular smooth muscle cell (VSMC), treatment of GSI significantly attenuated growth factor-induced VEGF and fibroblast growth factor-2 (FGF-2) expression. Indeed, GSI attenuated VEGF-induced tube formation and inhibited FGF-2-induced angiogenesis on matrigel in mice as quantified by FITC-lectin staining of EC. Overall, we demonstrated that {gamma}-secretase may be key molecule in postnatal angiogenesis which may be downstream molecule of growth factor-induced growth and migration in EC, and regulate the expression of angiogenic growth factors in VSMC.

  15. 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.

  16. Stressors during Pregnancy and the Postnatal Period.

    ERIC Educational Resources Information Center

    Field, Tiffany

    1989-01-01

    Some infants experience unusual stress from pregnancy through the postnatal period and are especially called upon to exercise coping responses. Discusses unusual stressors, how the infant naturally copes with them, and how caregivers can provide assistance. Reviews studies on stress-relieving intervention techniques. (NH)

  17. Recipient twin limb ischemia with postnatal onset.

    PubMed

    Broadbent, Roland Spencer

    2007-02-01

    After the occurrence of 3 local cases of limb ischemia in newborn twins, we reviewed the literature to investigate this combination systematically. This review reveals a distinct condition: postnatal onset limb ischemia affecting recipient twins in twin-twin transfusion syndrome.

  18. 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.

  19. Evaluation of postnatal growth of preterm infants.

    PubMed

    Bertino, Enrico; Di Nicola, Paola; Giuliani, Francesca; Coscia, Alessandra; Varalda, Alessia; Occhi, Luciana; Rossi, Claudia

    2011-10-01

    The past two decades have seen a progressive improvement in the survival rates of preterm infants, especially in neonates <30 weeks of gestational age. These neonates constitute the large majority of the population in neonatal intensive care units. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth, specifically in relation to the charts used. At present the available charts in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. An international multicentric project has recently started a study aiming at building a prescriptive standard for the evaluation of postnatal growth of preterm infants and it will be available in the next years providing a population that is conceptually as close as possible to the prescriptive approach used for the construction of the WHO infant and child growth standards. At present, while an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise in clinical practice is likely to be as follows: new Italian INeS (Italian Neonatal Study) charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to two years; finally the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006 growth charts could be suitable for monitoring the growth of these infants from two years up to 20 years of age.

  20. 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.

  1. Molecular architecture of DesV from Streptomyces venezuelae: a PLP-dependent transaminase involved in the biosynthesis of the unusual sugar desosamine.

    PubMed

    Burgie, E Sethe; Thoden, James B; Holden, Hazel M

    2007-05-01

    Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide antibiotics such as the commonly prescribed erythromycin. Six enzymes are required for its biosynthesis in Streptomyces venezuelae. The focus of this article is DesV, which catalyzes the PLP-dependent replacement of a 3-keto group with an amino functionality in the fifth step of the pathway. For this study the three-dimensional structures of both the internal aldimine and the ketimine intermediate with glutamate were determined to 2.05 A resolution. DesV is a homodimer with each subunit containing 12 alpha-helical regions and 12 beta-strands that together form three layers of sheet. The structure of the internal aldimine demonstrates that the PLP-cofactor is held in place by residues contributed from both subunits (Asp 164 and Gln 167 from Subunit I and Tyr 221 and Asn 235 from Subunit II). When the ketimine intermediate is present in the active site, the loop defined by Gln 225 to Ser 228 from Subunit II closes down upon the active site. The structure of DesV is similar to another sugar-modifying enzyme referred to as PseC. This enzyme is involved in the biosynthesis of pseudaminic acid, which is a sialic acid-like nonulosonate found in the flagellin of Helicobacter pylori. In the case of PseC, however, the amino group is transferred to the C-4 rather than the C-3 position. Details concerning the structural analysis of DesV and a comparison of its molecular architecture to that of PseC are presented.

  2. Postnatal Treatment in Antenatally Diagnosed Meconium Peritonitis.

    PubMed

    Ionescu, S; Andrei, B; Oancea, M; Licsandru, E; Ivanov, M; Marcu, V; Popa-Stanila, R; Mocanu, M

    2015-01-01

    Meconium peritonitis is a rare prenatal disease with an increased rate of morbidity and mortality in the neonatal period. Distinctive features revealed by prenatal and postnatal ultrasoundmay be present: abdominal calcifications, ascites, polyhydramnios, meconium pseudocyst, echogenic mass and dilated bowel or intestinal obstruction. Establishing clear postnatal treatment and prognosis is difficult because of the heterogeneity of the results obtained by ultrasound. The aim of the study is to determine how prenatal diagnosis of meconium peritonitis is associated with perinatal management and further evolution. Clinical results are different depending on the presence of antenatal diagnosis of meconium peritonitis and its form, which can be mild or severe. Surgical treatment and management of meconium peritonitis depend on the clinical presentation of the newborn. Meconium peritonitis diagnosed prenatally differs from that of the newborn, not only concerning the mortality rates but also through reduced morbidity and overall better prognosis.

  3. Post-natal myogenic and adipogenic developmental

    PubMed Central

    Konings, Gonda; van Weeghel, Michel; van den Hoogenhof, Maarten MG; Gijbels, Marion; van Erk, Arie; Schoonderwoerd, Kees; van den Bosch, Bianca; Dahlmans, Vivian; Calis, Chantal; Houten, Sander M; Misteli, Tom

    2011-01-01

    A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNAGT−/−) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. PMID:21818413

  4. Developmental origin of postnatal cardiomyogenic progenitor cells

    PubMed Central

    Liu, Yuan-Hung; Lai, Ling-Ping; Huang, Shih-Yun; Lin, Yi-Shuan; Wu, Shinn-Chih; Chou, Chih-Jen; Lin, Jiunn-Lee

    2016-01-01

    Aim: To trace the cell origin of the cells involved in postnatal cardiomyogenesis. Materials & methods: Nkx2.5 enhancer-eGFP (Nkx2.5 enh-eGFP) mice were used to test the cardiomyogenic potential of Nkx2.5 enhancer-expressing cells. By analyzing Cre excision of activated Nkx2.5-eGFP+ cells from different lineage-Cre/Nkx2.5 enh-eGFP/ROSA26 reporter mice, we traced the developmental origin of Nkx2.5 enhancer-expressing cells. Results: Nkx2.5 enhancer-expressing cells could differentiate into striated cardiomyocytes both in vitro and in vivo. Nkx2.5-eGFP+ cells increased remarkably after experimental myocardial infarction (MI). The post-MI Nkx2.5-eGFP+ cells originated from the embryonic epicardial cells, not from the pre-existing cardiomyocytes, endothelial cells, cardiac neural crest cells or perinatal/postnatal epicardial cells. Conclusion: Postnatal Nkx2.5 enhancer-expressing cells are cardiomyogenic progenitor cells and originate from embryonic epicardium-derived cells. PMID:28031967

  5. Neurodevelopmental Outcomes in Postnatal Growth-Restricted Preterm Infants with Postnatal Head-Sparing

    PubMed Central

    Meyers, Jeffrey M.; Bann, Carla M.; Stoll, Barbara J.; D’Angio, Carl T.; Bell, Edward F.; Duncan, Andrea F.; Guillet, Ronnie

    2016-01-01

    Objective To compare neurodevelopmental outcomes in postnatal growth-restricted infants born < 29 weeks with and without postnatal head-sparing. Study Design We analyzed developmental outcomes at 2 years of age among postnatally growth-restricted infants with and without head-sparing. The primary outcome was Bayley III cognitive composite score; secondary outcomes included Bayley III motor composite score, moderate/severe cerebral palsy, GMFCS level ≥2, and presence or absence of neurodevelopmental impairment (NDI). Results Of 1098 infants evaluated at 18–22 months, 658 were postnatally growth-restricted, of whom 301 had head-sparing. In the multivariate model including independent risk factors for poor growth and poor developmental outcome, infants with head-sparing had higher adjusted motor composite scores (mean difference 4.65, p<0.01), but no differences in other neurodevelopmental outcomes. Conclusion Postnatal head-sparing is associated with improved neurodevelopmental outcome in extremely preterm infants, specifically Bayley III motor scores, but whether beneficial effects of PHS persist later in life is unknown. PMID:27629374

  6. 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

  7. Epilepsy gene LGI1 regulates postnatal developmental remodeling of retinogeniculate synapses.

    PubMed

    Zhou, Yu-Dong; Zhang, Dawei; Ozkaynak, Ekim; Wang, Xuan; Kasper, Ekkehard M; Leguern, Eric; Baulac, Stéphanie; Anderson, Matthew P

    2012-01-18

    Retinogeniculate connections undergo postnatal refinement in the developing visual system. Here we report that non-ion channel epilepsy gene LGI1 (leucine-rich glioma-inactivated), mutated in human autosomal dominant lateral temporal lobe epilepsy (ADLTE), regulates postnatal pruning of retinal axons in visual relay thalamus. By introducing an ADLTE-associated truncated mutant LGI1 (836delC) or excess full-length LGI1 into transgenic mice, we found that mutant LGI1 blocks, whereas excess LGI1 accelerates, retinogeniculate axon pruning. The normal postnatal single fiber strengthening was arrested by mutant LGI1 and, contrastingly, was enhanced by excess wild-type LGI1. The maximum response of the retinogeniculate synapses, conversely, remained the same in mature LGI1 transgenic mice, indicating that mutant LGI1 blocks, whereas excess wild-type LGI1 promotes, weak axon fiber elimination. Heterozygous deletion of the LGI1 gene, as found in ADLTE patients, inhibited postnatal retinogeniculate synapse elimination, an effect similar to the ADLTE truncated mutant LGI1. The results identify sensory axon remodeling defects in a sensory aura-associated human epilepsy disorder.

  8. Childhood maltreatment, postnatal distress and the protective role of social support.

    PubMed

    Schury, K; Zimmermann, J; Umlauft, M; Hulbert, A L; Guendel, H; Ziegenhain, U; Kolassa, I-T

    2017-03-09

    The postpartum period is a vulnerable period for women with a history of childhood maltreatment. This study investigated the association between childhood maltreatment and postnatal distress three months postpartum and examined the role of social support provided by different sources (intimate partner, parents, parents-in-law, and friends). Analyses are based on N=66 women, who were screened for maltreatment experiences shortly after parturition with the Childhood Trauma Questionnaire. Their levels of postnatal distress (symptoms of depression, anxiety, and stress; assessed with the Hospital Anxiety and Depression Scale and the 4-Item version of the Perceived Stress Scale) and postpartum social support (measured with the Postpartum Social Support Questionnaire) were assessed three months postpartum. Adjusting for educational level and the experience of a recent stressful event, childhood maltreatment was directly associated with higher levels of postnatal distress. Social support provided by friends moderated this association in a heteroscedastic regression analysis. No moderating effect was observed for support provided by the own parents, the intimate partner, or parents-in-law. The association between childhood maltreatment and postnatal distress was not mediated by social support. Additional analyses revealed no main, moderating, or mediating effects of satisfaction with support. Results suggest that support provided by friends may promote resilience during the postpartum period in women with a history of childhood maltreatment. Efforts to better understand the role of postpartum support and mechanisms that may enhance a mother's ability to develop and maintain supportive friendships may be promising for guiding preventive interventions.

  9. Prenatal immunotoxicant exposure and postnatal autoimmune disease.

    PubMed Central

    Holladay, S D

    1999-01-01

    Reports in humans and rodents indicate that immune development may be altered following perinatal exposure to immunotoxic compounds, including chemotherapeutics, corticosteroids, polycyclic hydrocarbons, and polyhalogenated hydrocarbons. Effects from such exposure may be more dramatic or persistent than following exposure during adult life. For example, prenatal exposure to the insecticide chlordane or to the polycyclic aromatic hydrocarbon benzo[(italic)a(/italic)]pyrene produces what appears to be lifelong immunosuppression in mice. Whether prenatal immunotoxicant exposure may predispose the organism to postnatal autoimmune disease remains largely unknown. In this regard, the therapeutic immunosuppressant cyclosporin A (CsA) crosses the placenta poorly. However, lethally irradiated rodents exposed to CsA postsyngeneic bone marrow transplant (i.e., during re-establishment of the immune system) develop T-cell-mediated autoimmune disease, suggesting this drug may produce a fundamental disruption in development of self-tolerance by T cells. The environmental contaminant 2,3,7, 8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD) crosses the placenta and produces fetal thymic effects (italic)in vivo(/italic) similar to effects of CsA in fetal thymic organ culture, including inhibited thymocyte maturation and reduced expression of thymic major histocompatability complex class II molecules. These observations led to the suggestion that gestational exposure to TCDD may interfere with normal development of self-tolerance. Possibly supporting this hypothesis, when mice predisposed to development of autoimmune disease were treated with TCDD during gestation, postnatal autoimmunity was exacerbated. Similar results have been reported for mice exposed to diethylstilbestrol during development. These reports suggest that prenatal exposure to certain immunotoxicants may play a role in postnatal expression of autoimmunity. PMID:10502532

  10. Postnatal growth in term infants born small for gestational age is associated with later neurocognitive and metabolic outcomes.

    PubMed

    Castanys-Muñoz, Esther; Kennedy, Kathy; Castañeda-Gutiérrez, Eurídice; Forsyth, Stewart; Godfrey, Keith M; Koletzko, Berthold; Ozanne, Susan E; Rueda, Ricardo; Schoemaker, Marieke; van der Beek, Eline M; van Buuren, Stef; Ong, Ken K

    2017-04-06

    We systematically reviewed papers published in English between 1994 and October 2015 on how postnatal weight gain and growth affects neurodevelopment and metabolic outcomes in term-born small for gestational age (SGA) infants. Two randomised trials reported that enriched infant formulas that promoted early growth also increased fat mass, lean mass and blood pressure, but had no effect on early neurocognitive outcomes. Meanwhile, 31 observational studies reported consistent positive associations between postnatal weight gain and growth with neurocognitive outcomes, adiposity, insulin resistance and blood pressure.

  11. Postnatal Evaluation and Outcome of Prenatal Hydronephrosis

    PubMed Central

    Sadeghi-Bojd, Simin; Kajbafzadeh, Abdol-Mohammad; Ansari-Moghadam, Alireza; Rashidi, Somaye

    2016-01-01

    Background: Prenatal hydronephrosis (PNH) is dilation in urinary collecting system and is the most frequent neonatal urinary tract abnormality with an incidence of 1% to 5% of all pregnancies. PNH is defined as anteroposterior diameter (APD) of renal pelvis ≥ 4 mm at gestational age (GA) of < 33 weeks and APD ≥ 7 mm at GA of ≥ 33 weeks to 2 months after birth. All patients need to be evaluated after birth by postnatal renal ultrasonography (US). In the vast majority of cases, watchful waiting is the only thing to do; others need medical or surgical therapy. Objectives: There is a direct relationship between APD of renal pelvis and outcome of PNH. Therefore we were to find the best cutoff point APD of renal pelvis which leads to surgical outcome. Patients and Methods: In this retrospective cohort study we followed 200 patients 1 to 60 days old with diagnosis of PNH based on before or after birth ultrasonography; as a prenatal or postnatal detected, respectively. These patients were referred to the nephrology clinic in Zahedan Iran during 2011 to 2013. The first step of investigation was a postnatal renal US, by the same expert radiologist and classifying the patients into 3 groups; normal, mild/moderate and severe. The second step was to perform voiding cystourethrogram (VCUG) for mild/moderate to severe cases at 4 - 6 weeks of life. Tc-diethylene triamine-pentaacetic acid (DTPA) was the last step and for those with normal VCUG who did not show improvement in follow-up examination, US to evaluate obstruction and renal function. Finally all patients with mild/moderate to severe PNH received conservative therapy and surgery was preserved only for progressive cases, obstruction or renal function ≤35%. All patients’ data and radiologic information was recorded in separate data forms, and then analyzed by SPSS (version 22). Results: 200 screened PNH patients with male to female ratio 3.5:1 underwent first postnatal control US, of whom 65% had normal, 18% mild

  12. 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.

  13. Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation.

    PubMed

    Xavier, Guilherme M; Patist, Amanda L; Healy, Chris; Pagrut, Ankita; Carreno, Gabriela; Sharpe, Paul T; Martinez-Barbera, Juan Pedro; Thavaraj, Selvam; Cobourne, Martyn T; Andoniadou, Cynthia L

    2015-09-28

    In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma.

  14. Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation

    PubMed Central

    Xavier, Guilherme M.; Patist, Amanda L.; Healy, Chris; Pagrut, Ankita; Carreno, Gabriela; Sharpe, Paul T.; Pedro Martinez-Barbera, Juan; Thavaraj, Selvam; Cobourne, Martyn T.; Andoniadou, Cynthia L.

    2015-01-01

    In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma. PMID:26411543

  15. Postnatal cardiopulmonary adaptations to high altitude.

    PubMed

    Huicho, Luis

    2007-09-30

    Postnatal cardiopulmonary adaptations to high altitude constitute a key component of any set of responses developed to face high altitude hypoxia. Such responses are required ultimately to meet the energy demands necessary for adequate functioning at cell and organism level. After a brief insight on general and cardiopulmonary comparative studies in growing and adult organisms, differences and possible explanations for varying cardiopulmonary pathology, pulmonary artery hypertension, persistent right ventricular predominance and subacute high altitude pulmonary hypertension in different populations of children living at high altitude are discussed. Potential long-term implications of early chronic hypoxic exposure on later diseases are also presented. It is hoped that this review will help the practicing physician working at high altitude to make informed decisions concerning individual pediatric patients, specifically with regard to diagnosis and management of altitude-related cardiopulmonary pathology. Finally, plausibility and the knowledge-base of public health interventions to reduce the risks posed by suboptimal or inadequate postnatal cardiopulmonary responses to high altitude are discussed.

  16. Properties of persistent postnatal cortical subplate neurons.

    PubMed

    Torres-Reveron, Juan; Friedlander, Michael J

    2007-09-12

    Subplate (SP) neurons are important for the proper development of thalamocortical innervation. They are necessary for formation of ocular dominance and orientation columns in visual cortex. During the perinatal period, many SP neurons die. The surviving cohort forms interstitial cells in the white matter (WM) and a band of horizontally oriented cells below layer VI (layer VIb, layer VII, or subplate cells). Although the function of embryonic SP neurons has been well established, the functional roles of WM and postnatal SP cells are not known. We used a combination of anatomical, immunohistochemical, and electrophysiological techniques to explore the dendritic morphology, neurotransmitter phenotype, intrinsic electrophysiological, and synaptic input properties of these surviving cells in the rat visual cortex. The density of SP and WM cells significantly decreases during the first month of life. Both populations express neuronal markers and have extensive dendritic arborizations within the SP, WM, and to the overlying visual cortex. Some intrinsic electrophysiological properties of SP and WM cells are similar: each generates high-frequency slowly adapting trains of action potentials in response to a sustained depolarization. However, SP cells exhibit greater frequency-dependent action potential broadening than WM neurons. Both cell types receive predominantly AMPA/kainate receptor-mediated excitatory synaptic input that undergoes paired-pulse facilitation as well as NMDA receptor and GABAergic input. Synaptic inputs to these cells can also undergo long-term synaptic plasticity. Thus, surviving SP and WM cells are functional electrogenic neurons integrated within the postnatal visual cortical circuit.

  17. Fetal and postnatal ovine mesenteric vascular reactivity

    PubMed Central

    Nair, Jayasree; Gugino, Sylvia F.; Nielsen, Lori C.; Caty, Michael G.; Lakshminrusimha, Satyan

    2016-01-01

    BACKGROUND Intestinal circulation and mesenteric arterial (MA) reactivity may play a role in preparing the fetus for enteral nutrition. We hypothesized that MA vasoreactivity changes with gestation and vasodilator pathways predominate in the postnatal period. METHODS Small distal MA rings (0.5-mm diameter) were isolated from fetal (116-d, 128-d, 134-d, and 141-d gestation, term ~ 147 d) and postnatal lambs. Vasoreactivity was evaluated using vasoconstrictors (norepinephrine (NE) after pretreatment with propranolol and endothelin-1(ET-1)) and vasodilators (NO donors A23187 and s-nitrosopenicillamine (SNAP)). Protein and mRNA assays for receptors and enzymes (endothelin receptor A, alpha-adrenergic receptor 1A (ADRA1A), endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase5 (PDE5)) were performed in mesenteric arteries. RESULTS MA constriction to NE and ET-1 peaked at 134 d. Relaxation to A23187 and SNAP was maximal after birth. Basal eNOS activity was low at 134 d. ADRA1A mRNA and protein increasedsignificantlyat134danddecreasedpostnatally.sGC and PDE5 protein increased from 134 to 141 d. CONCLUSION Mesenteric vasoconstriction predominates in late-preterm gestation (134 d; the postconceptional age with the highest incidence of necrotizing enterocolitis (NEC)) followed by a conversion to vasodilatory influences near the time of full-term birth. Perturbations in this ontogenic mechanism, including preterm birth, may be a risk factor for NEC. PMID:26672733

  18. Roles of Notch1 Signaling in Regulating Satellite Cell Fates Choices and Postnatal Skeletal Myogenesis.

    PubMed

    Shan, Tizhong; Xu, Ziye; Wu, Weiche; Liu, Jiaqi; Wang, Yizhen

    2016-12-12

    Adult skeletal muscle stem cells, also called satellite cells, are indispensable for the growth, maintenance, and regeneration of the postnatal skeletal muscle. Satellite cells, predominantly quiescent in mature resting muscles, are activated after skeletal muscle injury or degeneration. Notch1 signaling is an evolutionarily conserved pathway that plays crucial roles in satellite cells homeostasis and postnatal skeletal myogenesis and regeneration. Activation of Notch1 signaling promotes the muscle satellite cells quiescence and proliferation, but inhibits differentiation of muscle satellite cells. Notably, the new roles of Notch1 signaling during late-stage of skeletal myogenesis including in post-differentiation myocytes and post-fusion myotubes have been recently reported. Here, we mainly review and discuss the regulatory roles of Notch1 in regulating satellite cell fates choices and skeletal myogenesis. This article is protected by copyright. All rights reserved.

  19. Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration

    SciTech Connect

    Kim, Chi-Kyeong; Hirose, Yuko; Sakudo, Akikazu; Takeyama, Natsumi; Kang, Chung-Boo; Taniuchi, Yojiro; Matsumoto, Yoshitsugu; Itohara, Shigeyoshi; Sakaguchi, Suehiro; Onodera, Takashi . E-mail: aonoder@mail.ecc.u-tokyo.ac.jp

    2007-06-29

    Splenocytes of wild-type (Prnp {sup +/+}) and prion protein gene-deficient (Prnp {sup -/-}) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) + ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP{sup C}) expression was enhanced following ConA stimulation, but not PMA + Io or LPS in Prnp {sup +/+} splenocytes. Rikn Prnp {sup -/-} splenocytes elicited lower cell proliferations than Prnp {sup +/+} or Zrch I Prnp {sup -/-} splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP{sup C} and PrPLP/Doppel.

  20. Stereospecificity of isotopic exchange of C-α-protons of glycine catalyzed by three PLP-dependent lyases: the unusual case of tyrosine phenol-lyase.

    PubMed

    Koulikova, Vitalia V; Zakomirdina, Lyudmila N; Gogoleva, Olga I; Tsvetikova, Marina A; Morozova, Elena A; Komissarov, Vsevolod V; Tkachev, Yaroslav V; Timofeev, Vladimir P; Demidkina, Tatyana V; Faleev, Nicolai G

    2011-11-01

    A comparative study of the kinetics and stereospecificity of isotopic exchange of the pro-2R- and pro-2S protons of glycine in (2)H(2)O under the action of tyrosine phenol-lyase (TPL), tryptophan indole-lyase (TIL) and methionine γ-lyase (MGL) was undertaken. The kinetics of exchange was monitored using both (1)H- and (13)C-NMR. In the three compared lyases the stereospecificities of the main reactions with natural substrates dictate orthogonal orientation of the pro-2R proton of glycine with respect to the cofactor pyridoxal 5'-phosphate (PLP) plane. Consequently, according to Dunathan's postulate with all the three enzymes pro-2R proton should exchange faster than does the pro-2S one. In fact the found ratios of 2R:2S reactivities are 1:20 for TPL, 108:1 for TIL, and 1,440:1 for MGL. Thus, TPL displays an unprecedented inversion of stereospecificity. A probable mechanism of the observed phenomenon is suggested, which is based on the X-ray data for the quinonoid intermediate, formed in the reaction of TPL with L-alanine. The mechanism implies different conformational changes in the active site upon binding of glycine and alanine. These changes can lead to relative stabilization of either the neutral amino group, accepting the α-proton, or the respective ammonium group, which is formed after the proton abstraction.

  1. Structures of a γ-aminobutyrate (GABA) transaminase from the s-triazine-degrading organism Arthrobacter aurescens TC1 in complex with PLP and with its external aldimine PLP–GABA adduct

    PubMed Central

    Bruce, Heather; Nguyen Tuan, Anh; Mangas Sánchez, Juan; Leese, Charlotte; Hopwood, Jennifer; Hyde, Ralph; Hart, Sam; Turkenburg, Johan P.; Grogan, Gideon

    2012-01-01

    Two complex structures of the γ-aminobutyrate (GABA) transaminase A1R958 from Arthrobacter aurescens TC1 are presented. The first, determined to a resolution of 2.80 Å, features the internal aldimine formed by reaction between the ∊-amino group of Lys295 and the cofactor pyridoxal phosphate (PLP); the second, determined to a resolution of 2.75 Å, features the external aldimine adduct formed between PLP and GABA in the first half-reaction. This is the first structure of a microbial GABA transaminase in complex with its natural external aldimine and reveals the molecular determinants of GABA binding in this enzyme. PMID:23027742

  2. Individual and Area Level Factors Associated with Prenatal, Delivery, and Postnatal Care in Pakistan.

    PubMed

    Budhwani, Henna; Hearld, Kristine Ria; Harbison, Hanne

    2015-10-01

    This research examines individual and area level factors associated with maternal health care utilization in Pakistan. The 2012-2013 Pakistan Demographic and Health Surveys data was used to model five outcomes: prenatal care within the first trimester, four plus prenatal visits, birth attendance by a skilled attendant, birth in a medical facility, and receipt of postnatal care. Less than half of births were to mothers receiving prenatal care in the first trimester, and approximately 57 % had trained personnel at delivery. Over half were born to mothers who received postnatal care. Evidence was found to support the positive effect of individual level variables, education and wealth, on the utilization of maternal health care across all five measures. Although, this study did not find unilateral differences between women residing in rural and urban settings, rural women were found to have lower odds of utilizing prenatal services as compared to mothers in urban environments. Additionally, women who cited distance as a barrier, had lower odds of receiving postnatal health care, but still engaged in prenatal services and often had a skilled attendant present at delivery. The odds of utilizing prenatal care increased when women resided in an area where prenatal utilization was high, and this variability was found across measures across provinces. The results found in this paper highlight the uneven progress made around improving prenatal, delivery, and postnatal care in Pakistan; disparities persist which may be attributed to factors both at the individual and community level, but may be addressed through a consorted effort to change national policy around women's health which should include the promotion of evidence based interventions such as incentivizing health care workers, promoting girls' education, and improving transportation options for pregnant women and recent mothers with the intent of ultimately lowering the Maternal Mortality Rate as recommended in the U

  3. Suppression of isotope scrambling in cell-free protein synthesis by broadband inhibition of PLP enymes for selective 15N-labelling and production of perdeuterated proteins in H2O.

    PubMed

    Su, Xun-Cheng; Loh, Choy-Theng; Qi, Ruhu; Otting, Gottfried

    2011-05-01

    Selectively isotope labelled protein samples can be prepared in vivo or in vitro from selectively labelled amino acids but, in many cases, metabolic conversions between different amino acids result in isotope scrambling. The best results are obtained by cell-free protein synthesis, where metabolic enzymes are generally less active, but isotope scrambling can never be suppressed completely. We show that reduction of E. coli S30 extracts with NaBH(4) presents a simple and inexpensive way to achieve cleaner selective isotope labelling in cell-free protein synthesis reactions. The purpose of the NaBH(4) is to inactivate all pyridoxal-phosphate (PLP) dependent enzymes by irreversible reduction of the Schiff bases formed between PLP and lysine side chains of the enzymes or amino groups of free amino acids. The reduced S30 extracts retain their activity of protein synthesis, can be stored as well as conventional S30 extracts and effectively suppress conversions between different amino acids. In addition, inactivation of PLP-dependent enzymes greatly stabilizes hydrogens bound to α-carbons against exchange with water, minimizing the loss of α-deuterons during cell-free production of proteins from perdeuterated amino acids in H(2)O solution. This allows the production of highly perdeuterated proteins that contain protons at all exchangeable positions, without having to back-exchange labile deuterons for protons as required for proteins that have been synthesized in D(2)O.

  4. Postnatal transmission of human immunodeficiency virus type 1: the breast-feeding dilemma.

    PubMed

    Van de Perre, P

    1995-08-01

    Human milk has been considered only recently as a source of transmission for the human immunodeficiency virus. The estimated postnatal transmission rate from mothers who acquired human immunodeficiency virus infection while lactating is 26% (95% confidence interval 13% to 39%) and may be in the range of 8% to 18% from mothers who were infected before becoming pregnant. Risk factors for postnatal transmission include maternal immune deficiency and the presence of human immunodeficiency virus-infected cells in milk. Some milk factors may be protective against postnatal transmission such as specific immunoglobulin A and immunoglobulin M and a molecule able to inhibit the binding of human immunodeficiency virus to CD4. In addition to its safety and its birth-spacing properties, breast-feeding provides immunologic protection and an ideal nutritional content to the infant. In a poor hygienic environment artificial feeding dramatically increases morbidity and mortality from diarrheal diseases and respiratory infections. Consequently, according to our current knowledge the World Health Organization and the United Nations Children's Fund reasonably recommend continuing breast-feeding promotion in women living in settings where infectious diseases and malnutrition are the primary causes of infant deaths such as in many developing countries. In settings where infectious diseases and malnutrition are not the primary causes of infant deaths, such as in most of the settings in the developed world, the advisory group recommends against breast-feeding for mothers with proved human immunodeficiency virus-1 infection.

  5. Developmental profiling of postnatal dentate gyrus progenitors provides evidence for dynamic cell-autonomous regulation

    PubMed Central

    Gilley, Jennifer A.; Yang, Cui-Ping; Kernie, Steven G.

    2009-01-01

    The dentate gyrus of the hippocampus is one of the most prominent regions in the postnatal mammalian brain where neurogenesis continues throughout life. There is tremendous speculation regarding the potential implications of adult hippocampal neurogenesis, though it remains unclear to what extent this ability becomes attenuated during normal aging, and what genetic changes in the progenitor population ensue over time. Using defined elements of the nestin promoter, we developed a transgenic mouse that reliably labels neural stem and early progenitors with green fluorescent protein (GFP). Using a combination of immunohistochemical and flow cytometry techniques, we characterized the progenitor cells within the dentate gyrus and created a developmental profile from postnatal day 7 (P7) until 6 months of age. In addition, we demonstrate that the proliferative potential of these progenitors is controlled at least in part by cell-autonomous cues. Finally, in order to identify what may underlie these differences, we performed stem cell-specific microarrays on GFP-expressing sorted cells from isolated P7 and postnatal day 28 (P28) dentate gyrus. We identified several differentially expressed genes that may underlie the functional differences that we observe in neurosphere assays from sorted cells and differentiation assays at these different ages. These data suggest that neural progenitors from the dentate gyrus are differentially regulated by cell-autonomous factors that change over time. PMID:20014381

  6. 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.

  7. 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

  8. A review of longitudinal studies on antenatal and postnatal depression.

    PubMed

    Underwood, Lisa; Waldie, Karen; D'Souza, Stephanie; Peterson, Elizabeth R; Morton, Susan

    2016-10-01

    Antenatal depression is a known risk factor for postnatal depression; both are common disorders associated with negative impacts on child development. Few studies have followed up women from pregnancy and through the postnatal period to explore how rates of depression change. This review evaluates recent evidence on depression during pregnancy and after childbirth. A search of Embase, PsychINFO, MEDLINE and Cochrane Reviews was carried out to identify longitudinal studies on antenatal and postnatal depression. Studies that measured depression during pregnancy and up to 1 year after childbirth were evaluated against a set of criteria (e.g. less than 50 % attrition). Of the initial 523 studies identified, 16 studies met the final inclusion criteria with a total of 35,419 women. The average rate of antenatal depression across these studies was 17 and 13 % postnatal depression. The longitudinal nature of the studies revealed that on average 39 % of those who experienced antenatal depression went on to have postnatal depression. Similarly, on average, 47 % of those with postnatal depression had also experienced antenatal depression. On average, almost 7 % of women reported significant depressive symptoms in pregnancy that persisted after childbirth. The review provided evidence that rates of depression tend to be higher during pregnancy than in the first year following childbirth. Furthermore, the longitudinal data show that there is much movement between the groups categorised as depressed or not depressed. There is evidence that postnatal depression is often a continuation of existing antenatal depression.

  9. [Postnatal neurogenesis and regenerative capabilities of the central nervous system (review)].

    PubMed

    Kalandarishvili, E L; Bukiia, R D; Taktakishvili, A D; Chichinadze, G V; Kharebava, I G

    2012-05-01

    Postnatal neurogenesis and regeneration opportunities of experimentally damaged areas of the cerebral cortex in various mammalian species were studied by the use of light and electron microscopy, autoradiography and transplantation. Back in the 70s of the 20th century by I. Mepisashvili and her school, it has been found that at the early stages of postnatal development of animals in the matrix area of the dorsolateral wall of the lateral ventricles there is a certain reserve of indifferent cells, which, like the embryonic period, by means of proliferation, migration and subsequent differentiation of their derivatives replenish the structure of the cortex with new glial and nerve cells and appear to be the major source of reparative regeneration of the CNS. The definite regularity in the rate of matrix cells implementation in the animals that occupy different levels of phylogenetic level (mouse, rat, rabbit, cat, dog) was established. It was found that in the immature-born animals (rabbit) the reserve of indifferent cells is maintained longer and their postnatal implementation takes place in a more extended period as compared to mature-born animals (guinea pig). The rates of the matrix cells implementation are in direct proportion to the functional load of the cerebral cortex. It has been demonstrated that these cells serve as the main source of regeneration of cortical lesions in the early postnatal period, while the defined biostimulants promote the intensification of this process. As a result of transplantation of the matrix of embryonic and early postembryonic cells in the experimentally damaged cortex of adult rats the quite successful restoration of the structure, characteristic of the relevant department of the cerebral cortex was observed.

  10. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    PubMed Central

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  11. Homeodomain Interacting Protein Kinase 2 Regulates Postnatal Development of Enteric Dopaminergic Neurons and Glia via BMP Signaling

    PubMed Central

    Chalazonitis, Alcmène; Tang, Amy A.; Shang, Yulei; Pham, Tuan D.; Hsieh, Ivy; Setlik, Wanda; Gershon, Michael D.; Huang, Eric J.

    2011-01-01

    Trophic factor signaling is important for the migration, differentiation and survival of enteric neurons during development. The mechanisms that regulate the maturation of enteric neurons in postnatal life, however, are poorly understood. Here, we show that transcriptional cofactor HIPK2 (homeodomain interacting protein kinase 2) is required for the maturation of enteric neurons and for regulating gliogenesis during postnatal development. Mice lacking HIPK2 display a spectrum of gastrointestinal (GI) phenotypes, including distention of colon and slowed GI transit time. Although loss of HIPK2 does not affect enteric neuron in prenatal development, a progressive loss of enteric neurons occurs during postnatal life in Hipk2−/− -mutant mice that preferentially affects the dopaminergic population of neurons in the caudal region of the intestine. The mechanism by which HIPK2 regulates postnatal enteric neuron development appears to involve the response of enteric neurons to bone morphogenetic proteins (BMPs). Specifically, compared to wild type mice, a larger proportion of enteric neurons in Hipk2−/−mutants have abnormally high level of phosphorylated Smad1/5/8. Consistent with the ability of BMP signaling to promote gliogenesis, Hipk2−/− mutants show a significant increase in glia in the ENS. In addition, numbers of autophagosomes are increased in enteric neurons in Hipk2−/−mutants and synaptic maturation is arrested. These results reveal a new role for HIPK2 as an important transcriptional cofactor that regulates the BMP signaling pathway in the maintenance of enteric neurons and glia, and further suggest that HIPK2 and its associated signaling mechanisms may be therapeutically altered to promote postnatal neuronal maturation. PMID:21957238

  12. Risk factors for antenatal depression, postnatal depression and parenting stress

    PubMed Central

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-01-01

    Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Methods Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program [1]. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Results Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors

  13. 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.

  14. Sonic hedgehog signaling in the postnatal brain.

    PubMed

    Álvarez-Buylla, Arturo; Ihrie, Rebecca A

    2014-09-01

    Sonic hedgehog (Shh) is a pleiotropic factor in the developing central nervous system (CNS), driving proliferation, specification, and axonal targeting in multiple sites within the forebrain, hindbrain, and spinal cord. Studies in embryonic CNS have shown how gradients of this morphogen are translated by neuroepithelial precursors to determine the types of neurons and glial cells they produce [1,2]. Shh also has a well-characterized role as a mitogen for specific progenitor cell types in neural development [3,4]. As we begin to appreciate that Shh continues to act in the adult brain, a central question is what functional role this ligand plays when major morphogenetic and proliferative processes are no longer in operation. A second fundamental question is whether similar signaling mechanisms operate in embryonic and adult CNS. In the two major germinal zones of the adult brain, Shh signaling modulates the self-renewal and specification of astrocyte-like primary progenitors, frequently referred to as neural stem cells (NSCs). It also may regulate the response of the mature brain to injury, as Shh signaling has been variously proposed to enhance or inhibit the development of a reactive astrocyte phenotype. The identity of cells producing the Shh ligand, and the conditions that trigger its release, are also areas of growing interest; both germinal zones in the adult brain contain Shh-responsive cells but do not autonomously produce this ligand. Here, we review recent findings revealing the function of this fascinating pathway in the postnatal and adult brain, and highlight ongoing areas of investigation into its actions long past the time when it shapes the developing brain.

  15. Postnatal ontogenesis of molecular clock in mouse striatum.

    PubMed

    Cai, Yanning; Liu, Shu; Li, Ning; Xu, Shengli; Zhang, Yanli; Chan, Piu

    2009-04-06

    Striatum is an important brain area whose function is related to motor, emotion and motivation. Interestingly, biological and physiological circadian rhythms have been found in the striatum extensively, suggesting molecular clock machinery works efficiently therein. However, the striatal expression profiles of clock genes have not been characterized systematically. In addition, little is known about when the expression rhythms start during postnatal ontogenesis. In the present study, 24 h mRNA oscillations of 6 principle clock genes (Bmal1, Clock, Npas2, Cry1, Per1 and Rev-erb alpha) were examined in mouse striatum, at early postnatal stage (postnatal day 3), pre-weaning stage (postnatal day 14) and in adult (postnatal day 60). At P3, no daily oscillation was found for all clock genes. At P14, a significant time effect was identified only for Rev-erb alpha and Npas2. At P60, the daily oscillations of these clock genes were at least borderline significant, with peak time at Circadian time (CT) 01 for Bmal1, Clock, Npas2 and Cry1; at CT 13 for Per1; and at CT 07 for Rev-erb alpha. In addition, the overall mean mRNA levels of these clock genes also underwent a dynamic change postnatally. For Bmal1, Clock, Npas2, Per1 and Rev-erb alpha, the expression level increased throughout the postnatal ontogenesis from P3, P14 to P60. For Cry1, however, the abundance at P3 and P60 were similar while that at P14 was much lower. In conclusion, the striatal molecular clock machinery, although works efficiently in adult, develops gradually after birth in mice.

  16. Selective Endothelin-B Receptor Stimulation Increases Vascular Endothelial Growth Factor in the Rat Brain during Postnatal Development.

    PubMed

    Leonard, M G; Prazad, P; Puppala, B; Gulati, A

    2015-11-01

    Endothelin, vascular endothelial growth factor and nerve growth factor play important roles in development of the central nervous system. ET(B) receptors have been shown to promote neurovascular remodeling in the adult ischemic brain through an increase in VEGF and NGF. It is possible that ET(B) receptors may be involved in postnatal development of the brain through VEGF and NGF. In the present study, the brains of male rat pups on postnatal days 1, 7, 14 and 28 were analyzed for expression of ET(B) receptors, VEGF and NGF. In order to determine the effect of ET(B) receptor stimulation, a separate group of pups were administered saline or ET(B) receptor agonist, IRL-1620, on day 21, and their brains were analyzed on day 28. The intensity of ET(B) receptor and VEGF staining in the vasculature as well as the number of blood vessels of normal pups increased with age and was significantly higher on postnatal day 14 compared to day 1 and day 7. In contrast, both ET(B) and NGF staining intensity in the cortex and subventricular zones decreased (P<0.01) at postnatal day 14 compared to earlier time points. Stimulation of ET(B) receptors resulted in a significant increase in VEGF and ET(B) intensity both in the vasculature and the brain (P<0.05), however, IRL-1620 did not produce any change in NGF expression. Results indicate that ET(B) receptors appear to play a role in the development of the CNS and selective stimulation of ET(B) receptors enhances VEGF but not NGF in the postnatal rat brain.

  17. Postnatal growth of preterm infants: which reference charts?

    PubMed

    Bertino, E; Gilli, G; Occhi, L; Giuliani, F; Di Nicola, P; Spada, E; Fabris, C

    2010-06-01

    Preterm Infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. These neonates constitute the large majority of the population in neonatal intensive care units. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth,specifically in relation to the charts used. At present the available charts in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. An international multicentric project has recently started a study aiming at building a prescriptive standard for the evaluation of postnatal growth of preterm infants and it will be available in the next years. At present, while an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise in clinical practice is likely to be as follows: new Italian INeS (Italian Neonatal Study) charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to two years; finally, the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006 growth charts could be suitable for monitoring the growth of these infants from two years up to 20 years of age.

  18. A woman-led approach to improving postnatal care.

    PubMed

    Fryer-Croxall, Claire; Bailey, Elizabeth

    2014-01-01

    As a large NHS teaching trust we see 6,000 women a year who birth with us. Newly appointed as a modern matron, I noted that poor experience on our postnatal ward has always been a key issue in the complaints we receive and from the feedback that our women give to us. The ImPosE (improving postnatal experience) project was launched in December 2013. This brought together members of the multidisciplinary team who were committed to developing our postnatal ward and improving it for our women and their families. We used a quality management approach, putting 'customer' experience at the core, and implemented a varied package of changes as directed by feedback from service users.

  19. 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

  20. Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

    PubMed Central

    Yu, Pujiao; Wang, Hongbao; Xie, Yuan; Zhou, Jinzhe

    2016-01-01

    The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases. PMID:28105427

  1. Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth.

    PubMed

    Yu, Pujiao; Wang, Hongbao; Xie, Yuan; Zhou, Jinzhe; Yao, Jianhua; Che, Lin

    2016-01-01

    The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs-miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p-were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

  2. Functional alpha7 nicotinic receptors are expressed on immature granule cells of the postnatal dentate gyrus.

    PubMed

    John, Danielle; Shelukhina, Irina; Yanagawa, Yuchio; Deuchars, Jim; Henderson, Zaineb

    2015-03-19

    Neurogenesis occurs throughout life in the subgranular zone of the dentate gyrus, and postnatal-born granule cells migrate into the granule cell layer and extend axons to their target areas. The α7*nicotinic receptor has been implicated in neuronal maturation during development of the brain and is abundant in interneurons of the hippocampal formation of the adult brain. Signalling through these same receptors is believed also to promote maturation and integration of adult-born granule cells in the hippocampal formation. We therefore aimed to determine whether functional α7*nicotinic receptors are expressed in developing granule cells of the postnatal dentate gyrus. For these experiments we used 2-3 week-old Wistar rats, and 2-9 week old transgenic mice in which GABAergic interneurons were marked by expression of green fluorescent protein. Immunohistochemistry indicated the presence of α7*nicotinic receptor subunits around granule cells close around the subgranular zone which correlated with the distribution of developmental markers for immature granule cells. Whole-cell patch clamp recording showed that a proportion of granule cells responded to puffed ACh in the presence of atropine, and that these cells possessed electrophysiological properties found in immature granule cells. The nicotinic responses were potentiated by an allosteric α7*nicotinic receptor modulator, which were blocked by a specific α7*nicotinic receptor antagonist and were not affected by ionotropic glutamate or GABA receptor antagonists. These results suggest the presence of functional somato-dendritic α7*nicotinic receptors on immature granule cells of the postnatal dentate gyrus, consistent with studies implicating α7*nicotinic receptors in dendritic maturation of dentate gyrus neurons in adult brain.

  3. Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration.

    PubMed

    Walters, Bradley J; Zuo, Jian

    2013-03-01

    The organ of Corti in the mammalian inner ear is comprised of mechanosensory hair cells (HCs) and nonsensory supporting cells (SCs), both of which are believed to be terminally post-mitotic beyond late embryonic ages. Consequently, regeneration of HCs and SCs does not occur naturally in the adult mammalian cochlea, though recent evidence suggests that these cells may not be completely or irreversibly quiescent at earlier postnatal ages. Furthermore, regenerative processes can be induced by genetic and pharmacological manipulations, but, more and more reports suggest that regenerative potential declines as the organ of Corti continues to age. In numerous mammalian systems, such effects of aging on regenerative potential are well established. However, in the cochlea, the problem of regeneration has not been traditionally viewed as one of aging. This is an important consideration as current models are unable to elicit widespread regeneration or full recovery of function at adult ages yet regenerative therapies will need to be developed specifically for adult populations. Still, the advent of gene targeting and other genetic manipulations has established mice as critically important models for the study of cochlear development and HC regeneration and suggests that auditory HC regeneration in adult mammals may indeed be possible. Thus, this review will focus on the pursuit of regeneration in the postnatal and adult mouse cochlea and highlight processes that occur during postnatal development, maturation, and aging that could contribute to an age-related decline in regenerative potential. Second, we will draw upon the wealth of knowledge pertaining to age related senescence in tissues outside of the ear to synthesize new insights and potentially guide future research aimed at promoting HC regeneration in the adult cochlea.

  4. Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice

    PubMed Central

    Nielsen, Corinne M.; Cuervo, Henar; Ding, Vivianne W.; Kong, Yupeng; Huang, Eric J.; Wang, Rong A.

    2014-01-01

    Arteriovenous malformations (AVMs) are tortuous vessels characterized by arteriovenous (AV) shunts, which displace capillaries and shunt blood directly from artery to vein. Notch signaling regulates embryonic AV specification by promoting arterial, as opposed to venous, endothelial cell (EC) fate. To understand the essential role of endothelial Notch signaling in postnatal AV organization, we used inducible Cre-loxP recombination to delete Rbpj, a mediator of canonical Notch signaling, from postnatal ECs in mice. Deletion of endothelial Rbpj from birth resulted in features of AVMs by P14, including abnormal AV shunting and tortuous vessels in the brain, intestine and heart. We further analyzed brain AVMs, as they pose particular health risks. Consistent with AVM pathology, we found cerebral hemorrhage, hypoxia and necrosis, and neurological deficits. AV shunts originated from capillaries (and possibly venules), with the earliest detectable morphological abnormalities in AV connections by P8. Prior to AV shunt formation, alterations in EC gene expression were detected, including decreased Efnb2 and increased Pai1, which encodes a downstream effector of TGFβ signaling. After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity. Deletion of Rbpj from adult ECs led to tortuosities in gastrointestinal, uterine and skin vascular beds, but had mild effects in the brain. Our results demonstrate a temporal requirement for Rbpj in postnatal ECs to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and AVM pathogenesis. PMID:25209249

  5. Functional alpha7 nicotinic receptors are expressed on immature granule cells of the postnatal dentate gyrus

    PubMed Central

    John, Danielle; Shelukhina, Irina; Yanagawa, Yuchio; Deuchars, Jim; Henderson, Zaineb

    2015-01-01

    Neurogenesis occurs throughout life in the subgranular zone of the dentate gyrus, and postnatal-born granule cells migrate into the granule cell layer and extend axons to their target areas. The α7⁎nicotinic receptor has been implicated in neuronal maturation during development of the brain and is abundant in interneurons of the hippocampal formation of the adult brain. Signalling through these same receptors is believed also to promote maturation and integration of adult-born granule cells in the hippocampal formation. We therefore aimed to determine whether functional α7⁎nicotinic receptors are expressed in developing granule cells of the postnatal dentate gyrus. For these experiments we used 2–3 week-old Wistar rats, and 2–9 week old transgenic mice in which GABAergic interneurons were marked by expression of green fluorescent protein. Immunohistochemistry indicated the presence of α7⁎nicotinic receptor subunits around granule cells close around the subgranular zone which correlated with the distribution of developmental markers for immature granule cells. Whole-cell patch clamp recording showed that a proportion of granule cells responded to puffed ACh in the presence of atropine, and that these cells possessed electrophysiological properties found in immature granule cells. The nicotinic responses were potentiated by an allosteric α7⁎nicotinic receptor modulator, which were blocked by a specific α7⁎nicotinic receptor antagonist and were not affected by ionotropic glutamate or GABA receptor antagonists. These results suggest the presence of functional somato-dendritic α7⁎nicotinic receptors on immature granule cells of the postnatal dentate gyrus, consistent with studies implicating α7⁎nicotinic receptors in dendritic maturation of dentate gyrus neurons in adult brain. PMID:25553616

  6. 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.

  7. Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

    PubMed

    Tan, J; Buache, E; Alpy, F; Daguenet, E; Tomasetto, C-L; Ren, G-S; Rio, M-C

    2014-07-31

    MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

  8. Connective tissue growth factor is required for skeletal development and postnatal skeletal homeostasis in male mice.

    PubMed

    Canalis, Ernesto; Zanotti, Stefano; Beamer, Wesley G; Economides, Aris N; Smerdel-Ramoya, Anna

    2010-08-01

    Connective tissue growth factor (CTGF), a member of the cysteine-rich 61 (Cyr 61), CTGF, nephroblastoma overexpressed (NOV) (CCN) family of proteins, is synthesized by osteoblasts, and its overexpression inhibits osteoblastogenesis and causes osteopenia. The global inactivation of Ctgf leads to defective endochondral bone formation and perinatal lethality; therefore, the consequences of Ctgf inactivation on the postnatal skeleton are not known. To study the function of CTGF, we generated Ctgf(+/LacZ) heterozygous null mice and tissue-specific null Ctgf mice by mating Ctgf conditional mice, where Ctgf is flanked by lox sequences with mice expressing the Cre recombinase under the control of the paired-related homeobox gene 1 (Prx1) enhancer (Prx1-Cre) or the osteocalcin promoter (Oc-Cre). Ctgf(+/LacZ) heterozygous mice exhibited transient osteopenia at 1 month of age secondary to decreased trabecular number. A similar osteopenic phenotype was observed in 1-month-old Ctgf conditional null male mice generated with Prx1-Cre, suggesting that the decreased trabecular number was secondary to impaired endochondral bone formation. In contrast, when the conditional deletion of Ctgf was achieved by Oc-Cre, an osteopenic phenotype was observed only in 6-month-old male mice. Osteoblast and osteoclast number, bone formation, and eroded surface were not affected in Ctgf heterozygous or conditional null mice. In conclusion, CTGF is necessary for normal skeletal development but to a lesser extent for postnatal skeletal homeostasis.

  9. Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages

    PubMed Central

    Gibbings, Sophie L.; Goyal, Rajni; Desch, A. Nicole; Leach, Sonia M.; Prabagar, Miglena; Atif, Shaikh M.; Bratton, Donna L.; Janssen, William

    2015-01-01

    Alveolar macrophages (AMs) reside on the luminal surfaces of the airways and alveoli where they maintain host defense and promote alveolar homeostasis by ingesting inhaled particulates and regulating inflammatory responses. Recent studies have demonstrated that AMs populate the lungs during embryogenesis and self-renew throughout life with minimal replacement by circulating monocytes, except under extreme conditions of depletion or radiation injury. Here we demonstrate that on a global scale, environment appears to dictate AM development and function. Indeed, transcriptome analysis of embryonic host-derived and postnatal donor-derived AMs coexisting within the same mouse demonstrated >98% correlation and overall functional analyses were similar. However, we also identified several genes whose expression was dictated by origin rather than environment. The most differentially expressed gene not altered by environment was Marco, a gene recently demonstrated to have enhancer activity in embryonic-derived but not postnatal-derived tissue macrophages. Overall, we show that under homeostatic conditions, the environment largely dictates the programming and function of AMs, whereas the expression of a small number of genes remains linked to the origin of the cell. PMID:26232173

  10. Post-natal development of the Reeler mouse cerebellum: An ultrastructural study.

    PubMed

    Castagna, Claudia; Aimar, Patrizia; Alasia, Silvia; Lossi, Laura

    2014-07-01

    Reelin, an extracellular protein promoting neuronal migration in brain areas with a laminar architecture, is missing in the Reeler mouse (reelin(-/-)). Several studies indicate that the protein is also necessary for correct dendritic outgrowth and synapse formation in the adult forebrain. By transmission electron microscopy, we characterize the development and synaptic organization of the cerebellar cortex in Reeler mice and wild type control littermates at birth, postnatal day (P) 5, 7, 10 and 15. Ultrastructural analysis shows deep alterations in cortical architecture and mispositioning of the Purkinje neurons (Pns), which remain deeply embedded in a central cellular mass within the white matter, with highly immature features. Quantitative examination shows that Reeler mice display: (i) a lower density of granule cells and a higher density of Pns, from P10; (ii) a lower density of synaptic contacts between Pn dendrites and parallel or climbing fibers, from P5; (iii) a lower density of synaptic contacts between basket cells and Pns, from P5; and (iv) a lower density of mossy fiber rosettes, from P10. Our results demonstrate that Reelin profoundly affects the structure and synaptic connectivity of post-natal mouse cerebellum.

  11. Relevé postnatal Rourke 2014

    PubMed Central

    Riverin, Bruno; Li, Patricia; Rourke, Leslie; Leduc, Denis; Rourke, James

    2015-01-01

    Résumé Objectif Mettre à jour la version de 2011 du Relevé postnatal Rourke (RPR) à la suite d’une révision des meilleures données probantes récentes sur le suivi de la santé des nourrissons et des enfants de la naissance jusqu’à l’âge de 5 ans. Qualité des données La qualité des données a été cotée en fonction de l’ancien système de classification du Groupe d’étude canadien sur les soins de santé préventifs (jusqu’à 2006) et l’approche de détermination, d’élaboration et d’évaluation des recommandations (GRADE). Message principal De nouveaux faits scientifiques ont été pris en compte dans les recommandations du RPR 2014 en ce qui a trait au suivi de la croissance, à la nutrition, à l’éducation et aux conseils, au développement, à l’examen physique et à l’immunisation. La croissance est surveillée à l’aide des courbes de l’Organisation mondiale de la Santé qui ont été révisées en 2014. On devrait introduire les aliments solides en fonction de l’état de préparation du nourrisson et ces produits devraient contenir du fer. Il n’est actuellement plus recommandé de retarder l’introduction des allergènes alimentaires courants pour prévenir les allergies. Il faut promouvoir l’utilisation d’une tasse sans couvercle au lieu d’une tasse à bec dès l’âge de 12 mois. La section sur l’éducation et les conseils porte sur les blessures causées par du mobilier instable, ainsi que l’utilisation d’un siège d’auto orienté vers l’arrière jusqu’à 2 ans. Elle comporte aussi de l’information sur les saines habitudes de sommeil, la prévention de la maltraitance des enfants, la vie saine et active et la sédentarité de la famille, de même que l’hygiène buccale. On a aussi ajouté à cette section une nouvelle catégorie consacrée à la santé environnementale pour tenir compte des effets des dangers environnementaux sur la santé des enfants. Le RPR a recours à une

  12. Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability

    PubMed Central

    Wyler, Steven C.; Spencer, W. Clay; Green, Noah H.; Rood, Benjamin D.; Crawford, LaTasha; Craige, Caryne; Gresch, Paul; McMahon, Douglas G.; Beck, Sheryl G.

    2016-01-01

    Newborn neurons enter an extended maturation stage, during which they acquire excitability characteristics crucial for development of presynaptic and postsynaptic connectivity. In contrast to earlier specification programs, little is known about the regulatory mechanisms that control neuronal maturation. The Pet-1 ETS (E26 transformation-specific) factor is continuously expressed in serotonin (5-HT) neurons and initially acts in postmitotic precursors to control acquisition of 5-HT transmitter identity. Using a combination of RNA sequencing, electrophysiology, and conditional targeting approaches, we determined gene expression patterns in maturing flow-sorted 5-HT neurons and the temporal requirements for Pet-1 in shaping these patterns for functional maturation of mouse 5-HT neurons. We report a profound disruption of postmitotic expression trajectories in Pet-1−/− neurons, which prevented postnatal maturation of 5-HT neuron passive and active intrinsic membrane properties, G-protein signaling, and synaptic responses to glutamatergic, lysophosphatidic, and adrenergic agonists. Unexpectedly, conditional targeting revealed a postnatal stage-specific switch in Pet-1 targets from 5-HT synthesis genes to transmitter receptor genes required for afferent modulation of 5-HT neuron excitability. 5-HT1a autoreceptor expression depended transiently on Pet-1, thus revealing an early postnatal sensitive period for control of 5-HT excitability genes. Chromatin immunoprecipitation followed by sequencing revealed that Pet-1 regulates 5-HT neuron maturation through direct gene activation and repression. Moreover, Pet-1 directly regulates the 5-HT neuron maturation factor Engrailed 1, which suggests Pet-1 orchestrates maturation through secondary postmitotic regulatory factors. The early postnatal switch in Pet-1 targets uncovers a distinct neonatal stage-specific function for Pet-1, during which it promotes maturation of 5-HT neuron excitability. SIGNIFICANCE STATEMENT The

  13. 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…

  14. Postnatal histomorphogenesis of the mandible in the house mouse.

    PubMed

    Martinez-Maza, Cayetana; Montes, Laëtitia; Lamrous, Hayat; Ventura, Jacint; Cubo, Jorge

    2012-05-01

    The mandible of the house mouse, Mus musculus, is a model structure for the study of the development and evolution of complex morphological systems. This research describes the histomorphogenesis of the house mouse mandible and analyses its biological significance from the first to the eighth postnatal weeks. Histological data allowed us to test a hypothesis concerning modularity in this structure. We measured the bone growth rates by fluorescent labelling and identified the bone tissue types through microscopic analysis of histological cross-sections of the mandible during its postnatal development. The results provide evidence for a modular structure of the mouse mandible, as the alveolar region and the ascending ramus show histological differences throughout ontogeny. The alveolar region increases in length during the first two postnatal weeks by bone growth in the posterior region, while horizontally positioned incisors preclude bone growth in the anterior region. In the fourth postnatal week, growth dynamics shows a critical change. The alveolar region drifts laterally and the ramus becomes more vertical due to the medial growth direction of the coronoid region and the lateral growth of the ventral region of the ramus. Diet changes after weaning are probably involved in these morphological changes. In this way, the development of the masticatory muscles that insert on the ascending ramus may be particularly related to this shape modeling of the house mouse mandible.

  15. POSTNATAL INFLAMMATION IN THE PATHOGENESIS OF BRONCHOPULMONARY DYSPLASIA

    PubMed Central

    Bhandari, Vineet

    2014-01-01

    Exposure to hyperoxia, invasive mechanical ventilation and systemic/local sepsis are important antecedents of postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia (BPD). This review will summarize information obtained from animal (baboon, lamb/sheep, rat and mouse) models that pertain to the specific inflammatory agents and signaling molecules that predispose a premature infant to BPD. PMID:24578018

  16. Microfibril Structure Masks Fibrillin-2 in Postnatal Tissues*

    PubMed Central

    Charbonneau, Noe L.; Jordan, C. Diana; Keene, Douglas R.; Lee-Arteaga, Sui; Dietz, Harry C.; Rifkin, Daniel B.; Ramirez, Francesco; Sakai, Lynn Y.

    2010-01-01

    Fibrillin microfibrils are polymeric structures present in connective tissues. The importance of fibrillin microfibrils to connective tissue function has been demonstrated by the multiple genetic disorders caused by mutations in fibrillins and in microfibril-associated molecules. However, knowledge of microfibril structure is limited, largely due to their insolubility. Most previous studies have focused on how fibrillin-1 is organized within microfibril polymers. In this study, an immunochemical approach was used to circumvent the insolubility of microfibrils to determine the role of fibrillin-2 in postnatal microfibril structure. Results obtained from studies of wild type and fibrillin-1 null tissues, using monoclonal and polyclonal antibodies with defined epitopes, demonstrated that N-terminal fibrillin-2 epitopes are masked in postnatal microfibrils and can be revealed by enzymatic digestion or by genetic ablation of Fbn1. From these studies, we conclude that fetal fibrillin polymers form an inner core within postnatal microfibrils and that microfibril structure evolves as growth and development proceed into the postnatal period. Furthermore, documentation of a novel cryptic site present in EGF4 in fibrillin-1 underscores the molecular complexity and tissue-specific differences in microfibril structure. PMID:20404337

  17. Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment

    PubMed Central

    Ding, Xue-Feng; Gao, Xiang; Ding, Xin-Chun; Fan, Ming; Chen, Jinhui

    2016-01-01

    Deficits in the Notch pathway are involved in a number of neurologic diseases associated with mental retardation or/and dementia. The mechanisms by which Notch dysregulation are associated with mental retardation and dementia are poorly understood. We found that Notch1 is highly expressed in the adult-born immature neurons in the hippocampus of mice. Retrovirus mediated knockout of notch1 in single adult-born immature neurons decreases mTOR signaling and compromises their dendrite morphogenesis. In contrast, overexpression of Notch1 intracellular domain (NICD), to constitutively activate Notch signaling in single adult-born immature neurons, promotes mTOR signaling and increases their dendrite arborization. Using a unique genetic approach to conditionally and selectively knockout notch 1 in the postnatally born immature neurons in the hippocampus decreases mTOR signaling, compromises their dendrite morphogenesis, and impairs spatial learning and memory. Conditional overexpression of NICD in the postnatally born immature neurons in the hippocampus increases mTOR signaling and promotes dendrite arborization. These data indicate that Notch signaling plays a critical role in dendrite development of immature neurons in the postnatal brain, and dysregulation of Notch signaling in the postnatally born neurons disrupts their development and thus contributes to the cognitive deficits associated with neurological diseases. PMID:27173138

  18. A complex postnatal mental health intervention: Australian translational formative evaluation.

    PubMed

    Rowe, Heather J; Wynter, Karen H; Burns, Joanna K; Fisher, Jane R W

    2016-01-07

    Reducing the burden of postnatal maternal mental health problems is an international public health priority. We developed What Were We Thinking (WWWT), a psychoeducation programme for primary postnatal health care that addresses known but neglected risks. We then demonstrated evidence of its effects in a before-and-after controlled study in preventing maternal postnatal mental health problems among women without a psychiatric history participating in the intervention compared to usual care (AOR 0.43; 95% CI 0.21, 0.89) when conducted by specialist nurses. Testing its effectiveness when implemented in routine primary care requires changes at practitioner, organizational and health system levels. This paper describes a programme of translational formative evaluation to inform the protocol for a cluster RCT. Following the UK Medical Research Council (MRC) Guidance for evaluating complex interventions, we conducted a translational formative evaluation using mixed methods. Collection and analysis of postnatal health service documents, semi-structured interviews, group discussions and an online survey were used to investigate service provision, consumers' needs and expectations, clinicians' attitudes and clinical practice, and the implications for health service delivery. Participants were expectant parents, health care providers, health service managers and government policy makers. Results documented current clinical practice, staff training needs, necessary service modifications to standardize advice to parents and include fathers, key priorities and drivers of government health policy, and informed a model of costs and expected health and social outcomes. Implementation of WWWT into routine postnatal care requires adjustments to clinical practice. Staff training, modifications to service opening hours and economic implications for the health system also need to be considered. The MRC Guidance for developing and evaluating complex interventions is a useful framework

  19. Postnatal Depression and Infant Health Practices among High-Risk Women

    ERIC Educational Resources Information Center

    Zajicek-Farber, Michaela L.

    2009-01-01

    Women's postnatal depressive symptoms have been associated with many adverse outcomes for children. The current study examined the frequency association with relative risk between postnatal depressive symptoms and mothers' use of preventative infant health practices. The study used the Edinburgh Postnatal Depression Scale (EPDS) and Parental…

  20. Predictors of Intelligence at the Age of 5: Family, Pregnancy and Birth Characteristics, Postnatal Influences, and Postnatal Growth

    PubMed Central

    Eriksen, Hanne-Lise Falgreen; Kesmodel, Ulrik Schiøler; Underbjerg, Mette; Kilburn, Tina Røndrup; Bertrand, Jacquelyn; Mortensen, Erik Lykke

    2013-01-01

    Parental education and maternal intelligence are well-known predictors of child IQ. However, the literature regarding other factors that may contribute to individual differences in IQ is inconclusive. The aim of this study was to examine the contribution of a number of variables whose predictive status remain unclarified, in a sample of basically healthy children with a low rate of pre- and postnatal complications. 1,782 5-year-old children sampled from the Danish National Birth Cohort (2003–2007) were assessed with a short form of the Wechsler Preschool and Primary Scale of Intelligence – Revised. Information on parental characteristics, pregnancy and birth factors, postnatal influences, and postnatal growth was collected during pregnancy and at follow-up. A model including study design variables and child’s sex explained 7% of the variance in IQ, while parental education and maternal IQ increased the explained variance to 24%. Other predictors were parity, maternal BMI, birth weight, breastfeeding, and the child’s head circumference and height at follow-up. These variables, however, only increased the explained variance to 29%. The results suggest that parental education and maternal IQ are major predictors of IQ and should be included routinely in studies of cognitive development. Obstetrical and postnatal factors also predict IQ, but their contribution may be of comparatively limited magnitude. PMID:24236109

  1. Why don't some women attend antenatal and postnatal care services?: a qualitative study of community members' perspectives in Garut, Sukabumi and Ciamis districts of West Java Province, Indonesia

    PubMed Central

    2010-01-01

    community members perceived health services to be necessary only if obstetric complications occurred. The services of traditional birth attendants for antenatal, delivery, and postnatal care were widely used, and their roles in maternal and child care were considered vital by some community members. Conclusions It is important that public health strategies take into account the availability, affordability and accessibility of health services. Poverty alleviation strategies will help financially deprived communities to use antenatal and postnatal health services. This study also demonstrated the importance of health promotion programs for increasing community awareness about the necessity of antenatal and postnatal services. PMID:20937146

  2. 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

  3. Hippocampal HDAC4 contributes to postnatal fluoxetine-evoked depression-like behavior.

    PubMed

    Sarkar, Ambalika; Chachra, Parul; Kennedy, Pamela; Pena, Catherine J; Desouza, Lynette A; Nestler, Eric J; Vaidya, Vidita A

    2014-08-01

    Fluoxetine treatment in adulthood evokes antidepressant and anxiolytic responses. Paradoxically, postnatal fluoxetine (PNFlx) induces persistent depression- and anxiety-like behaviors. The mechanistic underpinnings of this paradox remain poorly understood. Here, we examined specific molecular changes in the rat hippocampus that accompany perturbed emotionality observed across life following PNFlx. PNFlx-induced hippocampal gene regulation observed in microarray and quantitative PCR studies indicate functional enrichment of genes involved in response to organic substances, protein kinase pathways, DNA binding, and transcriptional repression. We noted specific transcripts (Hdac4, mammalian target of rapamycin (mTOR), Gnai1, protein kinase C gamma (Prkcc), and hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1)) that were consistently dysregulated across life, and selectively influenced by postnatal, but not adult, fluoxetine. Increased histone deacetylase-4 (HDAC4) recruitment, accompanied by decreased activating histone acetylation marks at the mTOR and Gnai1 promoters, indicate a role for HDAC4 in PNFlx-mediated gene dysregulation. Strikingly, coadministration of the HDAC inhibitor sodium butyrate with PNFlx prevented the dysregulation of Hdac4 and mTOR, and the emergence of depression- and anxiety-like behavior. Importantly, we also find that retreatment of PNFlx animals with fluoxetine in adulthood reversed the increased Hdac4 expression, prevented HDAC4 recruitment to the mTOR and Gnai1 promoters, and attenuated the decline in mTOR and Gnai1 expression, coincident with normalization of PNFlx-evoked depression- and anxiety-like behavior. Further, we show that viral-mediated hippocampal overexpression of Hdac4 was sufficient to induce depression-, but not anxiety-, like behavior in adulthood. Our results highlight the unique nature of molecular signatures evoked by PNFlx, and implicate HDAC4 in the dysregulated gene expression and emergence of

  4. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    SciTech Connect

    Blossom, Sarah J.; Cooney, Craig A.; Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J.; Wessinger, William D.

    2013-06-15

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  5. Connexin expression in electrically coupled postnatal rat brain neurons

    PubMed Central

    Venance, Laurent; Rozov, Andrei; Blatow, Maria; Burnashev, Nail; Feldmeyer, Dirk; Monyer, Hannah

    2000-01-01

    Electrical coupling by gap junctions is an important form of cell-to-cell communication in early brain development. Whereas glial cells remain electrically coupled at postnatal stages, adult vertebrate neurons were thought to communicate mainly via chemical synapses. There is now accumulating evidence that in certain neuronal cell populations the capacity for electrical signaling by gap junction channels is still present in the adult. Here we identified electrically coupled pairs of neurons between postnatal days 12 and 18 in rat visual cortex, somatosensory cortex, and hippocampus. Notably, coupling was found both between pairs of inhibitory neurons and between inhibitory and excitatory neurons. Molecular analysis by single-cell reverse transcription–PCR revealed a differential expression pattern of connexins in these identified neurons. PMID:10944183

  6. 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

  7. Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

    PubMed Central

    Tam, Emily W. Y.; Chau, Vann; Ferriero, Donna M.; Barkovich, A. James; Poskitt, Kenneth J.; Studholme, Colin; Fok, Eric D.-Y.; Grunau, Ruth E.; Glidden, David V.; Miller, Steven P.

    2012-01-01

    With improving survival rates of preterm newborns, adverse cognitive outcomes are increasingly recognized. Adverse cognitive outcomes are associated with decreased cerebellar volumes, and modifiable risk factors for these adverse outcomes should be identified. Animal models demonstrate reduced preterm cerebellar growth after exposure to glucocorticoids. Preterm neonates were prospectively studied with serial MRI examinations near birth and again near term-equivalent age. Adjusting for associated clinical factors, antenatal bethamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone were associated with impaired cerebellar, but not cerebral, growth. Modifying postnatal risk factors for impaired cerebellar development, and particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth. PMID:22013125

  8. Organotypic slice cultures for studies of postnatal neurogenesis.

    PubMed

    Mosa, Adam J; Wang, Sabrina; Tan, Yao Fang; Wojtowicz, J Martin

    2015-03-04

    Here we describe a technique for studying hippocampal postnatal neurogenesis in the rodent brain using the organotypic slice culture technique. This method maintains the characteristic topographical morphology of the hippocampus while allowing direct application of pharmacological agents to the developing hippocampal dentate gyrus. Additionally, slice cultures can be maintained for up to 4 weeks and thus, allow one to study the maturation process of newborn granule neurons. Slice cultures allow for efficient pharmacological manipulation of hippocampal slices while excluding complex variables such as uncertainties related to the deep anatomic location of the hippocampus as well as the blood brain barrier. For these reasons, we sought to optimize organotypic slice cultures specifically for postnatal neurogenesis research.

  9. Organotypic Slice Cultures for Studies of Postnatal Neurogenesis

    PubMed Central

    Mosa, Adam J.; Wang, Sabrina; Tan, Yao Fang; Wojtowicz, J. Martin

    2015-01-01

    Here we describe a technique for studying hippocampal postnatal neurogenesis in the rodent brain using the organotypic slice culture technique. This method maintains the characteristic topographical morphology of the hippocampus while allowing direct application of pharmacological agents to the developing hippocampal dentate gyrus. Additionally, slice cultures can be maintained for up to 4 weeks and thus, allow one to study the maturation process of newborn granule neurons. Slice cultures allow for efficient pharmacological manipulation of hippocampal slices while excluding complex variables such as uncertainties related to the deep anatomic location of the hippocampus as well as the blood brain barrier. For these reasons, we sought to optimize organotypic slice cultures specifically for postnatal neurogenesis research. PMID:25867138

  10. 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.

  11. Ion channels in postnatal neurogenesis: potential targets for brain repair.

    PubMed

    Swayne, Leigh Anne; Wicki-Stordeur, Leigh

    2012-01-01

    Neural stem and progenitor cells (NSC/NPCs) are unspecialized cells found in the adult peri-ventricular and sub-granular zones that are capable of self-renewal, migration, and differentiation into new neurons through the remarkable process of postnatal neurogenesis. We are now beginning to understand that the concerted action of ion channels, multi-pass transmembrane proteins that allow passage of ions across otherwise impermeable cellular membranes tightly regulate this process. Specific ion channels control proliferation, differentiation and survival. Furthermore, they have the potential to be highly selective drug targets due to their complex structures. As such, these proteins represent intriguing prospects for control and optimization of postnatal neurogenesis for neural regeneration following brain injury or disease. Here, we concentrate on ion channels identified in adult ventricular zone NSC/NPCs that have been found to influence the stages of neurogenesis. Finally, we outline the potential of these channels to elicit repair, and highlight the outstanding challenges.

  12. 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.

  13. Postnatal ontogeny and the evolution of macrostomy in snakes

    PubMed Central

    2016-01-01

    Macrostomy is the anatomical feature present in macrostomatan snakes that permits the ingestion of entire prey with high cross-sectional area. It depends on several anatomical traits in the skeleton and soft tissues, of which the elongation of gnathic complex and backward rotation of the quadrate represent crucial skeletal requirements. Here, the relevance of postnatal development of these skull structures and their relationship with macrohabitat and diet are explored. Contrary to the condition present in lizards and basal snakes that occupy underground macrohabitats, elements of the gnathic complex of most macrostomatan snakes that exploit surface macrohabitats display conspicuous elongation during postnatal growth, relative to the rest of the skull, as well as further backward rotation of the quadrate bone. Remarkably, several clades of small cryptozoic macrostomatans reverse these postnatal transformations and return to a diet based on prey with low cross-sectional area such as annelids, insects or elongated vertebrates, thus resembling the condition present in underground basal snakes. Dietary ontogenetic shift observed in most macrostomatan snakes is directly linked with this ontogenetic trajectory, indicating that this shift is acquired progressively as the gnathic complex elongates and the quadrate rotates backward during postnatal ontogeny. The numerous independent events of reversion in the gnathic complex and prey type choice observed in underground macrostomatans and the presence of skeletal requirements for macrostomy in extinct non-macrostomatan species reinforce the possibility that basal snakes represent underground survivors of clades that had the skeletal requirements for macrostomy. Taken together, the data presented here suggest that macrostomy has been shaped during multiple episodes of occupation of underground and surface macrohabitats throughout the evolution of snakes. PMID:28018652

  14. A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

    PubMed Central

    Adzick, N. Scott; Thom, Elizabeth A.; Spong, Catherine Y.; Brock, John W.; Burrows, Pamela K.; Johnson, Mark P.; Howell, Lori J.; Farrell, Jody A.; Dabrowiak, Mary E.; Sutton, Leslie N.; Gupta, Nalin; Tulipan, Noel B.; D'Alton, Mary E.; Farmer, Diana L.

    2013-01-01

    Background Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair. Methods We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function. Results The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P = 0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. Conclusions Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.) PMID:21306277

  15. Disrupting effect of androgens in postnatal female domestic cats.

    PubMed

    Demaldé, Lucía; Lopez Merlo, Mariana; Vercellini, Rosario; Barbeito, Claudio G; Fernandez, Patricia; Gobello, Cristina

    2016-08-01

    To test the hypothesis that in domestic cats, postnatal androgens induce sterility, the aims of this study were to describe the reproductive effects and the clinical safety of a postnatal administration of a long term release androgen in this species. Thirteen newborn littermate female kittens were randomly assigned to one of the following treatment groups within the first 24h of birth: testosterone enanthate 12.5mg sc (TE; n=8) or Placebo (PL; n=5). The animals were subsequently assessed for fecal sexual hormones until puberty was attained and subsequently when matings occurred. After 21 days, ovulation and gestation were diagnosed. All queens were subsequently ovario-hysterectomized. Fecal testosterone concentrations differed between the treatment groups throughout the study period (P<0.05) being greater during the first 2 postnatal weeks in those of the TE group (P<0.01). Fecal estradiol was not affected by treatment (P>0.1). While all the females were receptive during the pubertal estrus (P>0.1), two TE (2/8) compared with all (5/5) females of the PL group had ovulations (P<0.05). Only one (1/2) compared with three (3/5) of the queens of the TE and PL groups, respectively became pregnant. All kittens of the TE group had transient clitoral enlargement. Anovulatory TE-treated cats had no corpus luteum, and a significant diminution of the endometrial glands as well as of the height of the uterine epithelium. It is concluded that, in domestic cats, a single postnatal supra-physiological dose of testosterone caused a large proportion of queens to be anovulatory and there were also histological endometrial abnormalities that also occurred with this treatment that were accompanied by mild and transient side effects.

  16. Effect of GnRH analogs in postnatal domestic cats.

    PubMed

    Carranza, A; Faya, M; Merlo, M Lopez; Batista, P; Gobello, C

    2014-07-01

    The aim of this study was to reproductively assess the clinical and hormonal effects of a GnRH agonist (AG) and an antagonist (AN) administered during the postnatal period in domestic cats. Forty-eight male and female postnatal kittens were randomly assigned to deslorelin acetate 1.6 mg subcutaneous (AG; n = 16), acyline 33 μg/100 g subcutaneous weekly for 3 months (AN; n = 16), or control (CO; n = 16) which remained untreated. The cats were followed up (behavioral observation, physical examination, fecal sexual steroid determinations, mating test, and pregnancy diagnosis) up to puberty. Puberty was delayed (weeks) in the AG animals (62.9 ± 3.5; P < 0.01) but not in the AN (15.5 ± 1.7; P > 0.05) when they were compared with CO kittens (13.4 ± 0.4). Fifteen (15/16) of the AN and CO animals, and only 11 of 16 cats of the AG group were fertile (P > 0.1). No differences were found in body weight (P > 0.1) and measurements (P > 0.1), libido (P > 0.1) and in the appearance of side effects (P > 0.1; except a pyometra in an AG female) among groups. In both AG- and AN-treated males (testosterone; P < 0.01) and females (estradiol-17β; P < 0.01) fecal hormone concentrations were lower than in CO group during the first five postnatal weeks but not later. It is concluded that the neonatal administration of these AG and AN decreased fecal sexual steroids during the first postnatal weeks causing, the agonists but not the antagonist, a significant, reversible delay in puberty appearance.

  17. Loss of Runx2 in committed osteoblasts impairs postnatal skeletogenesis.

    PubMed

    Adhami, Mitra D; Rashid, Harunur; Chen, Haiyan; Clarke, John C; Yang, Yang; Javed, Amjad

    2015-01-01

    The Runx2 transcription factor is critical for commitment to the osteoblast lineage. However, its role in committed osteoblasts and its functions during postnatal skeletogenesis remain unclear. We established a Runx2-floxed line with insertion of loxP sites around exon 8 of the Runx2 gene. The Runx2 protein lacking the region encoded by exon 8 is imported into the nucleus and binds target DNA but exhibits diminished transcriptional activity. We specifically deleted the Runx2 gene in committed osteoblasts using 2.3-kb col1a-Cre transgenic mice. Surprisingly, the homozygous Runx2 mutant mice were born alive. The Runx2 heterozygous and homozygous null were grossly indistinguishable from wild-type littermates at birth. Runx2 deficiency did not alter proliferative capacity of osteoblasts during embryonic development (E18). Chondrocyte differentiation and cartilage growth in mutants was similar to wild-type mice from birth to 3 months of age. Analysis of the embryonic skeleton revealed poor calcification in homozygous mutants, which was more evident in bones formed by intramembranous ossification. Runx2 mutants showed progressive retardation in postnatal growth and exhibited significantly low bone mass by 1 month of age. Decreased bone formation was associated with decreased gene expression of osteoblast markers and impaired collagen assembly in the extracellular matrix. Consequently, Runx2 mutant bones exhibited decreased stiffness and structural integrity. By 3 months of age, bone acquisition in mutant mice was roughly half that of wild-type littermates. In addition to impaired osteoblast function, mutant mice showed markedly decreased osteoclast number and postnatal bone resorption. Taken together, functional deficiency of Runx2 in osteoblasts does not result in failed embryonic skeletogenesis but disrupts postnatal bone formation.

  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. The role of alternative medicine in treating postnatal depression.

    PubMed

    Mantle, Fiona

    2002-11-01

    Postnatal depression is a serious and debilitating condition. Due to the perceived stigma of mental illness, the incidence of it is underreported and many mothers refuse psychiatric help either assuming postnatal depression to be normal or because of the potential consequences of having a psychiatric history. Community practitioners who are in contact with new mothers may welcome additional interventions which can enhance the supportive care they give to these women. This article discusses the evidence for a number of these interventions which mothers may find more acceptable than orthodox treatment. The aim of this article is to highlight the possible role of a number of complementary and alternative medicines as adjuncts or alternative treatments for postnatal depression. The interventions discussed in this article include Ayurvedic medicine, herbalism, homeopathy, aromatherapy, massage, hypnosis and traditional Chinese medicine (TCM). With the exception of TCM and Ayurvedic medicine, these interventions have been supported by the House of Lord's Select Committee on Science and Technology (2000) as having an evidence base. Ayurvedic medicine and TCM have been included in this article however, because a number of clients may be using them as their main system of health care--thereby validating the need for information regarding their efficacy. This article is not exhaustive, nor a licence to practice, but is intended as a resource for practitioners with a sound understanding of postnatal depression and conventional treatments whose clients may reject these approaches and be looking for alternative interventions. The final choice of treatment should be the result of discussion between the health visitor and the client and will depend on considerations such as availability, cost and acceptability of the intervention--this article does not, therefore, suggest a 'best option' approach. In addition, it does not address the professional and legal responsibilities of

  20. Prenatal exposure to ethanol affects postnatal neurogenesis in thalamus.

    PubMed

    Mooney, Sandra M; Miller, Michael W

    2010-06-01

    The number of neurons in the ventrobasal thalamus (VB) in the adolescent rat is unaffected by prenatal exposure to ethanol. This is in sharp contrast to other parts of the trigeminal-somatosensory system, which exhibit 30-35% fewer neurons after prenatal ethanol exposure. The present study tested the hypothesis that prenatal ethanol exposure affects dynamic changes in the numbers of VB neurons; such changes reflect the sum of cell proliferation and death. Neuronal number in the VB was determined during the first postnatal month in the offspring of pregnant Long-Evans rats fed an ethanol-containing diet or pair-fed an isocaloric non-alcoholic liquid diet. Offspring were examined between postnatal day (P) 1 and P30. The size of the VB and neuronal number were determined stereologically. Prenatal exposure to ethanol did not significantly alter neuronal number on any individual day, nor was the prenatal generation of VB neurons affected. Interestingly, prenatal ethanol exposure did affect the pattern of the change in neuronal number over time; total neuronal number was stable in the ethanol-treated pups after P12, but it continued to rise in the controls until P21. In addition, the rate of cell proliferation during the postnatal period was greater in ethanol-treated animals. Thus, the rate of neuronal acquisition is altered by ethanol, and by deduction, there appears to be less ethanol-induced neuronal loss in the VB. A contributor to these changes is a latent effect of ethanol on postnatal neurogenesis in the VB and the apparent survival of new neurons.

  1. Postnatal ontogeny and the evolution of macrostomy in snakes.

    PubMed

    Scanferla, Agustín

    2016-11-01

    Macrostomy is the anatomical feature present in macrostomatan snakes that permits the ingestion of entire prey with high cross-sectional area. It depends on several anatomical traits in the skeleton and soft tissues, of which the elongation of gnathic complex and backward rotation of the quadrate represent crucial skeletal requirements. Here, the relevance of postnatal development of these skull structures and their relationship with macrohabitat and diet are explored. Contrary to the condition present in lizards and basal snakes that occupy underground macrohabitats, elements of the gnathic complex of most macrostomatan snakes that exploit surface macrohabitats display conspicuous elongation during postnatal growth, relative to the rest of the skull, as well as further backward rotation of the quadrate bone. Remarkably, several clades of small cryptozoic macrostomatans reverse these postnatal transformations and return to a diet based on prey with low cross-sectional area such as annelids, insects or elongated vertebrates, thus resembling the condition present in underground basal snakes. Dietary ontogenetic shift observed in most macrostomatan snakes is directly linked with this ontogenetic trajectory, indicating that this shift is acquired progressively as the gnathic complex elongates and the quadrate rotates backward during postnatal ontogeny. The numerous independent events of reversion in the gnathic complex and prey type choice observed in underground macrostomatans and the presence of skeletal requirements for macrostomy in extinct non-macrostomatan species reinforce the possibility that basal snakes represent underground survivors of clades that had the skeletal requirements for macrostomy. Taken together, the data presented here suggest that macrostomy has been shaped during multiple episodes of occupation of underground and surface macrohabitats throughout the evolution of snakes.

  2. 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.

  3. Prenatal and postnatal prevalence of Turner's syndrome: a registry study.

    PubMed Central

    Gravholt, C. H.; Juul, S.; Naeraa, R. W.; Hansen, J.

    1996-01-01

    OBJECTIVE--To study prevalence of Turner's syndrome in Denmark and to assess validity of prenatal diagnosis. DESIGN--Study of data on prenatal and postnatal Turner's syndrome in Danish Cytogenetic Central Register. SUBJECTS--All registered Turner's syndrome karyotypes (100 prenatal cases and 215 postnatal cases) during 1970-93. MAIN OUTCOME MEASURES--Prevalence of Turner's syndrome karyotypes among prenatally tested fetuses and Turner's syndrome among liveborn infants. RESULTS--Among infant girls, prevalence of Turner's syndrome was 32/100,000. Among female fetuses tested by amniocentesis, prevalence of Turner's syndrome karyotypes was 176/100,000 (relative risk of syndrome, 6.74 compared with prevalence among untested pregnancies). Among female fetuses tested by chorion villus sampling, prevalence of syndrome karyotypes was 392/100,000 (relative risk, 16.8). We excluded prenatal tests referred because of results of ultrasound scanning: among fetuses tested by amniocentesis revised relative risk was 5.68, while revised relative risk among fetuses tested by chorion villus sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turner's syndrome, pregnancy was allowed to continue and 24 children were live born. Thirteen of these children were karyotyped postnatally, and diagnosis of Turner's syndrome had to be revised for eight, seven being normal girls and one boy. This gives tentative predictive value of amniocentesis in diagnosing Turner's syndrome of between 21% and 67%. There was no significant relation between mother's age and risk of Turner's syndrome. CONCLUSIONS--Discrepancy between prenatal and postnatal prevalence of Turner's syndrome challenges specificity of prenatal examination in diagnosing Turner's syndrome. PMID:8555850

  4. Postnatal in-vivo MRI findings in anencephaly.

    PubMed

    Poretti, A; Meoded, A; Ceritoglu, E; Boltshauser, E; Huisman, T A G M

    2010-12-01

    We report on the MRI findings of an anencephalic infant who survived 10 weeks postnatally. MRI showed absence of the cranial vault, all supratentorial structures, and the cerebellum. A brainstem primordium without pontine prominence was present. The brainstem was surrounded by the area cerebrovasculosa. The absence of a pontine prominence in an anencephalic infant without cerebellar tissue supports the hypothesis that absent pontine prominence is found in children with a prenatal loss of cerebellar tissue.

  5. Neurotoxicity from prenatal and postnatal exposure to methylmercury

    PubMed Central

    Grandjean, Philippe; Weihe, Pal; Debes, Frodi; Choi, Anna L.; Budtz-Jørgensen, Esben

    2014-01-01

    The extent to which postnatal methylmercury exposure contributes to neurobehavioral delays is uncertain. Confounding may occur because the child's dietary exposure likely correlates with the mother's. This conundrum was examined in the Faroese birth cohort 1 born in 1986–1987. Exposure parameters included mercury concentrations in maternal hair at parturition, cord blood, and child blood and hair at the age-7 clinical examination (N = 923). In regression analyses, the child's current blood-mercury at age 7 (N = 694) showed only weak associations with the neuropsychological test variables, but visuospatial memory revealed a significant negative association. Mutual adjustment caused decreases of the apparent effect of the prenatal exposure. However, such adjustment may lead to underestimations due to the presence of correlated, error-prone exposure variables. In structural equation models, all methylmercury exposure parameters were instead entered into a latent exposure variable that reflected the total methylmercury load. This latent exposure showed significant associations with neurodevelopmental deficits, with prenatal exposure providing the main information. However, postnatal methylmercury exposure appeared to contribute to neurotoxic effects, in particular in regard to visuospatial processing and memory. Thus, addition in the regression analysis of exposure information obtained at a different point in time was not informative and should be avoided. Further studies with better information on exposure profiles are needed to characterize the effects of postnatal methylmercury exposure. PMID:24681285

  6. Prenatal presentation and postnatal management of congenital thoracic malformations.

    PubMed

    Bush, Andrew

    2009-11-01

    The antenatal finding of a congenital thoracic malformation (CTM) leads to anxiety in the parents and uncertainty as to the optimal management. The antenatal spectrum of CTM includes congenital cystic adenomatoid malformation, sequestration, congenital lobar emphysema, enteric and bronchogenic cysts, and bronchial atresia. Most lesions require no antenatal intervention, and shrink substantially in the third trimester, but if fetal hydrops develops, then antenatal intervention is required, occasionally medical but more usually surgical, because mortality is high. If the baby is symptomatic in the newborn period, then some form of surgical intervention is clearly required. The asymptomatic baby presents a therapeutic dilemma. Advocates of early surgery point to the complications of CTM, which include infection, pneumothorax, bleeding and malignant transformation. Those who are proponents of conservative management retort that some CTM disappear postnatally, and that the complication rate is unknown; many children appear never to need surgery. Furthermore, there is clearcut evidence that excision of a CTM does not totally eliminate the risk of a subsequent malignancy. It is clear that, both antenatally and postnatally, counselling of the family on a case by case basis is needed. The limitations of present evidence should be stressed. Different families will make different decisions about postnatal surgery in an asymptomatic baby. If surgery is performed, morbidity is low, particularly with a video-assisted thoracoscopic (VATS) procedure.

  7. Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation

    PubMed Central

    2012-01-01

    Background Pannexin 1 forms ion and metabolite permeable hexameric channels and is abundantly expressed in the brain. After discovering pannexin 1 expression in postnatal neural stem and progenitor cells we sought to elucidate its functional role in neuronal development. Results We detected pannexin 1 in neural stem and progenitor cells in vitro and in vivo. We manipulated pannexin 1 expression and activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell proliferation likely through the release of adenosine triphosphate (ATP). Conclusions Permeable to ATP, a potent autocrine/paracine signaling metabolite, pannexin 1 channels are ideally suited to influence the behavior of neural stem and progenitor cells. Here we demonstrate they play a robust role in the regulation of neural stem and progenitor cell proliferation. Endogenous postnatal neural stem and progenitor cells are crucial for normal brain health, and their numbers decline with age. Furthermore, these special cells are highly responsive to neurological injury and disease, and are gaining attention as putative targets for brain repair. Therefore, understanding the fundamental role of pannexin 1 channels in neural stem and progenitor cells is of critical importance for brain health and disease. PMID:22458943

  8. Postnatal ethanol exposure disrupts signal detection in adult rats.

    PubMed

    Woolfrey, Kevin M; Hunt, Pamela S; Burk, Joshua A

    2005-01-01

    Human prenatal ethanol exposure that occurs during a period of increased synaptogenesis known as the "brain growth spurt" has been associated with significant impairments in attention, learning, and memory. The present experiment assessed whether administration of ethanol during the brain growth spurt in the rat, which occurs shortly after birth, disrupts attentional performance. Rats were administered 5.25 g/kg/day ethanol via intragastric intubation from postnatal days (PD) 4-9, sham-intubation, or no intubation (naïve). Beginning at PD 90, animals were trained to asymptotic performance in a two-lever attention task that required discrimination of brief visual signals from trials with no signal presentation. Finally, manipulations of background noise and inter-trial interval duration were conducted. Early postnatal ethanol administration did not differentially affect acquisition of the attention task. However, after rats were trained to asymptotic performance levels, those previously exposed to ethanol demonstrated a deficit in detection of signals but not of non-signals compared to sham-intubated and naïve rats. The signal detection deficit persisted whenever these animals were re-trained in the standard task, but further task manipulations failed to interact with ethanol pretreatment. The present data support the hypothesis that early postnatal ethanol administration disrupts aspects of attentional processing in the rat.

  9. RASGRF2 controls nuclear migration in postnatal retinal cone photoreceptors.

    PubMed

    Jimeno, David; Gómez, Carmela; Calzada, Nuria; de la Villa, Pedro; Lillo, Concepción; Santos, Eugenio

    2016-02-15

    Detailed immunocytochemical analyses comparing wild-type (WT), GRF1-knockout (KO), GRF2-KO and GRF1/2 double-knockout (DKO) mouse retinas uncovered the specific accumulation of misplaced, 'ectopic' cone photoreceptor nuclei in the photoreceptor segment (PS) area of retinas from GRF2-KO and GRF1/2-DKO, but not of WT or GRF1-KO mice. Localization of ectopic nuclei in the PS area of GRF2-depleted retinas occurred postnatally and peaked between postnatal day (P)11 and P15. Mechanistically, the generation of this phenotype involved disruption of the outer limiting membrane and intrusion into the PS layer by cone nuclei displaying significant perinuclear accumulation of signaling molecules known to participate in nuclear migration and cytoskeletal reorganization, such as PAR3, PAR6 and activated, phosphorylated forms of PAK, MLC2 and VASP. Electroretinographic recordings showed specific impairment of cone-mediated retinal function in GRF2-KO and GRF1/2-DKO retinas compared with WT controls. These data identify defective cone nuclear migration as a novel phenotype in mouse retinas lacking GRF2 and support a crucial role of GRF2 in control of the nuclear migration processes required for proper postnatal development and function of retinal cone photoreceptors.

  10. Postnatal growth of the heart and its blood vessels.

    PubMed

    Hudlicka, O; Brown, M D

    1996-01-01

    Although rapid growth of the heart during early postnatal development ceases with maturation of the organism, the potential for cardiomyocyte growth is not lost and may be observed even in senescent hearts. Rapid developmental heart growth is accompanied by a proportional growth of capillaries but not always of larger vessels, and thus coronary vascular resistance gradually increases. Growth of adult hearts can be enhanced by thyroid hormones, catecholamines and the renin-angiotensin system hormones, but these do not always stimulate growth of coronary vessels. Likewise, chronic exposure to hypoxia leads to growth, mainly of the right ventricle and its vessels but without vascular growth elsewhere in the heart. On the other hand, ischaemia is a potent stimulus for the release of various growth factors involved in the development of collateral circulation. Heart hypertrophy develops in response to training, pressure or volume overload. Training usually leads to growth of larger coronary vessels but little growth of capillaries, except in young animals. However, growth of the capillary bed, but not the resistance vasculature capacity, can be induced by either increased coronary blood flow, bradycardia (electrically or pharmacologically induced) or increased inotropism, all of which are involved in the training stimulus. Thus, what actually promotes growth of larger vessels as opposed to capillaries in training is unclear. Pressure overload hypertrophy is mediated by both the renin-angiotensin system and the response of cardiomyocytes to stretch; both lead to activation of early oncogenes (c-fos, c-jun, c-myc) and angiotensin II activates several protein kinases involved in cell growth. In this condition, growth of larger vessels is inadequate, although some capillary growth may occur. Volume overload leads to cardiomyocyte hypertrophy and hyperplasia and some increase in vascular supply. Deficits in capillary supply in pressure or volume overload hypertrophy can be

  11. TNFα reverse signaling promotes sympathetic axon growth and target innervation

    PubMed Central

    Kisiswa, Lilian; Osório, Catarina; Erice, Clara; Vizard, Thomas; Wyatt, Sean; Davies, Alun M

    2013-01-01

    Reverse signaling via members of the tumor necrosis factor (TNF) superfamily is increasingly recognized among cells of the immune system where it controls multiple aspects of immune function. Here we document TNFα reverse signaling in the nervous system for the first time and show that it plays a crucial role in establishing sympathetic innervation. During postnatal development, sympathetic axons express TNFα as they grow and branch in their target tissues which in turn express TNFR1. In culture, soluble forms of TNFR1 act directly on postnatal sympathetic axons to promote growth and branching by a mechanism that depends on membrane integrated TNFα and downstream MEK/ERK activation. Sympathetic innervation density is significantly reduced in several tissues in postnatal and adult mice lacking either TNFα or TNFR1. These findings reveal that target-derived TNFR1 acts as a reverse signaling ligand for membrane-integrated TNFα to promote sympathetic axon growth and branching. PMID:23749144

  12. Role of thyroid hormone in postnatal circulatory and metabolic adjustments.

    PubMed Central

    Breall, J A; Rudolph, A M; Heymann, M A

    1984-01-01

    To assess the role of the early postnatal surge in plasma thyroid hormone concentrations on cardiovascular and metabolic adaptations, we measured cardiac output, total oxygen consumption, and plasma triiodothyronine (T3) concentrations in three groups of lambs in the first 6 h after delivery. 15 fetal lambs were prepared at gestational ages of 128-129 d by placing catheters in the brachiocephalic artery, descending aorta, distal inferior vena cava, left atrium, and pulmonary artery so that measurements could be made soon after delivery. They were divided into three groups: Group I comprised five control animals; Group II consisted of five fetuses in which thyroidectomy was performed at surgery at 129 d gestation; and Group III consisted of five animals in which thyroidectomy was performed at term gestation during delivery by caesarian section, prior to severing the umbilical cord. The lambs in Group I exhibited a rapid postnatal rise in T3 concentrations, similar to that described previously, reaching a peak value of about 5 ng/ml. Although the postnatal surge in T3 concentration was arrested in Group II and III animals, Group II had no detectable plasma T3, while the Group III animals had T3 concentrations of about 0.8 ng/ml, which were within the range previously reported for term lamb fetuses. The lambs in group II showed 40-50% lower left ventricular outputs (190 vs. 297 ml/kg per min), systemic blood flows (155 vs. 286 ml/kg per min), and oxygen consumptions (9.8 vs. 20.2 ml/kg per min) as compared with Group I animals over the entire 6-h period. The lambs in Group II also had significantly lower heart rates (131 vs. 192 beats/min) and mean systemic arterial pressures (56 vs. 72 torr). However, there were no significant differences for any of these measurements between the Group III and Group I lambs. The reduction in cardiac output in the Group II animals were reflected in a significantly lower blood flow to the peripheral circulation, but there were no

  13. Coaching to promote professional development in nursing practice.

    PubMed

    Narayanasamy, Aru; Penney, Vivian

    This article presents coaching, which facilitates the highest form of learning, as a potential strategy for promoting professional development in nursing. In doing so, it sets out what coaching is and highlights its benefits in terms of team building, adaptation to changes, career planning and professional development. Having established the rudiments of coaching and identifying its qualities, the article then sets out strategies of coaching using three models: the 3-D Technique Model, The Practice Spiral Model and The Grow Model. Three case histories are presented to explain how these models could be used to implement coaching and personal learning plans (PLP). Directions are provided where training for coaching is available. It is concluded that coaching can be a powerful tool in enhancing nurses' and other health professionals' ability to contribute to the success of healthcare organisations.

  14. The effectiveness of exercise as a treatment for postnatal depression: study protocol

    PubMed Central

    2012-01-01

    Background Postnatal depression can have a substantial impact on the woman, the child and family as a whole. Thus, there is a need to examine different ways of helping women experiencing postnatal depression; encouraging them to exercise may be one way. A meta analysis found some support for exercise as an adjunctive treatment for postnatal depression but the methodological inadequacy of the few small studies included means that it is uncertain whether exercise reduces symptoms of postnatal depression. We aim to determine whether a pragmatic exercise intervention that involves one-to-one personalised exercise consultations and telephone support plus usual care in women with postnatal depression, is superior to usual care only, in reducing symptoms of postnatal depression. Methods We aim to recruit 208 women with postnatal depression in the West Midlands. Recently delivered women who meet the ICD-10 diagnosis for depression will be randomised to usual care plus exercise or usual care only. The exercise intervention will be delivered over 6 months. The primary outcome measure is difference in mean Edinburgh Postnatal Depression Scale score between the groups at six month follow-up. Outcome measures will be assessed at baseline and at six and 12 month post randomisation. Discussion Findings from the research will inform future clinical guidance on antenatal and postnatal mental health, as well as inform practitioners working with postnatal depression. Trial registration number ISRCTN84245563 PMID:22682671

  15. GRP78 plays an essential role in adipogenesis and postnatal growth in mice

    PubMed Central

    Zhu, Genyuan; Ye, Risheng; Jung, Dae Young; Barron, Ernesto; Friedline, Randall H.; Benoit, Vivian M.; Hinton, David R.; Kim, Jason K.; Lee, Amy S.

    2013-01-01

    To investigate the role of GRP78 in adipogenesis and metabolic homeostasis, we knocked down GRP78 in mouse embryonic fibroblasts and 3T3-L1 preadipocytes induced to undergo differentiation into adipocytes. We also created an adipose Grp78-knockout mouse utilizing the aP2 (fatty acid binding protein 4) promoter-driven Cre-recombinase. Adipogenesis was monitored by molecular markers and histology. Tissues were analyzed by micro-CT and electron microscopy. Glucose homeostasis and cytokine analysis were performed. Our results indicate that GRP78 is essential for adipocyte differentiation in vitro. aP2-cre-mediated GRP78 deletion leads to lipoatrophy with ∼90% reduction in gonadal and subcutaneous white adipose tissue and brown adipose tissue, severe growth retardation, and bone defects. Despite severe abnormality in adipose mass and function, adipose Grp78-knockout mice showed normal plasma triglyceride levels, and plasma glucose and insulin levels were reduced by 40-60% compared to wild-type mice, suggesting enhanced insulin sensitivity. The endoplasmic reticulum is grossly expanded in the residual mutant white adipose tissue. Thus, these studies establish that GRP78 is required for adipocyte differentiation, glucose homeostasis, and balanced secretion of adipokines. Unexpectedly, the phenotypes and metabolic parameters of the mutant mice, which showed early postnatal mortality, are uniquely distinct from previously characterized lipodystrophic mouse models.—Zhu, G., Ye, R., Jung, D. Y., Barron, E., Friedline, R. H., Benoit, V. M., Hinton, D. R., Kim, J. K., Lee, A. S. GRP78 plays an essential role in adipogenesis and postnatal growth in mice. PMID:23180827

  16. RhoE Deficiency Produces Postnatal Lethality, Profound Motor Deficits and Neurodevelopmental Delay in Mice

    PubMed Central

    Arqué, Gloria; Poch, Enric; Peris, Blanca; Guerri, Consuelo; Dierssen, Mara; Guasch, Rosa M.; Terrado, José; Pérez-Roger, Ignacio

    2011-01-01

    Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt) are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD) 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders. PMID:21552537

  17. Differential neuronal plasticity in mouse hippocampus associated with various periods of enriched environment during postnatal development.

    PubMed

    Hosseiny, Salma; Pietri, Mariel; Petit-Paitel, Agnès; Zarif, Hadi; Heurteaux, Catherine; Chabry, Joëlle; Guyon, Alice

    2015-11-01

    Enriched environment (EE) is characterized by improved conditions for enhanced exploration, cognitive activity, social interaction and physical exercise. It has been shown that EE positively regulates the remodeling of neural circuits, memory consolidation, long-term changes in synaptic strength and neurogenesis. However, the fine mechanisms by which environment shapes the brain at different postnatal developmental stages and the duration required to induce such changes are still a matter of debate. In EE, large groups of mice were housed in bigger cages and were given toys, nesting materials and other equipment that promote physical activity to provide a stimulating environment. Weaned mice were housed in EE for 4, 6 or 8 weeks and compared with matched control mice that were raised in a standard environment. To investigate the differential effects of EE on immature and mature brains, we also housed young adult mice (8 weeks old) for 4 weeks in EE. We studied the influence of onset and duration of EE housing on the structure and function of hippocampal neurons. We found that: (1) EE enhances neurogenesis in juvenile, but not young adult mice; (2) EE increases the number of synaptic contacts at every stage; (3) long-term potentiation (LTP) and spontaneous and miniature activity at the glutamatergic synapses are affected differently by EE depending on its onset and duration. Our study provides an integrative view of the role of EE during postnatal development in various mechanisms of plasticity in the hippocampus including neurogenesis, synaptic morphology and electrophysiological parameters of synaptic connectivity. This work provides an explanation for discrepancies found in the literature about the effects of EE on LTP and emphasizes the importance of environment on hippocampal plasticity.

  18. Essential childbirth and postnatal interventions for improved maternal and neonatal health

    PubMed Central

    2014-01-01

    Childbirth and the postnatal period, spanning from right after birth to the following several weeks, presents a time in which the number of deaths reported still remain alarmingly high. Worldwide, about 800 women die from pregnancy- or childbirth-related complications daily while almost 75% of neonatal deaths occur within the first seven days of delivery and a vast majority of these occur in the first 24 hours. Unfortunately, this alarming trend of mortality persists, as287,000 women lost their lives to pregnancy and childbirth related causes in 2010. Almost all of these deaths were preventable and occurred in low-resource settings, pointing towards dearth of adequate facilities in these parts of the world. The main objective of this paper is to review the evidence based childbirth and post natal interventions which have a beneficial impact on maternal and newborn outcomes. It is a compilation of existing, new and updated interventions designed to help physicians and policy makers and enable them to reduce the burden of maternal and neonatal morbidities and mortalities. Interventions during the post natal period that were found to be associated with a decrease in maternal and neonatal morbidity and mortality included: advice and support of family planning, support and promotion of early initiation and continued breastfeeding; thermal care or kangaroo mother care for preterm and/or low birth weight babies; hygienic care of umbilical cord and skin following delivery, training health personnel in basic neonatal resuscitation; and postnatal visits. Adequate delivery of these interventions is likely to bring an unprecedented decrease in the number of deaths reported during childbirth. PMID:25177795

  19. Essential childbirth and postnatal interventions for improved maternal and neonatal health.

    PubMed

    Salam, Rehana A; Mansoor, Tarab; Mallick, Dania; Lassi, Zohra S; Das, Jai K; Bhutta, Zulfiqar A

    2014-01-01

    Childbirth and the postnatal period, spanning from right after birth to the following several weeks, presents a time in which the number of deaths reported still remain alarmingly high. Worldwide, about 800 women die from pregnancy- or childbirth-related complications daily while almost 75% of neonatal deaths occur within the first seven days of delivery and a vast majority of these occur in the first 24 hours. Unfortunately, this alarming trend of mortality persists, as 287,000 women lost their lives to pregnancy and childbirth related causes in 2010. Almost all of these deaths were preventable and occurred in low-resource settings, pointing towards dearth of adequate facilities in these parts of the world. The main objective of this paper is to review the evidence based childbirth and post natal interventions which have a beneficial impact on maternal and newborn outcomes. It is a compilation of existing, new and updated interventions designed to help physicians and policy makers and enable them to reduce the burden of maternal and neonatal morbidities and mortalities. Interventions during the post natal period that were found to be associated with a decrease in maternal and neonatal morbidity and mortality included: advice and support of family planning, support and promotion of early initiation and continued breastfeeding; thermal care or kangaroo mother care for preterm and/or low birth weight babies; hygienic care of umbilical cord and skin following delivery, training health personnel in basic neonatal resuscitation; and postnatal visits. Adequate delivery of these interventions is likely to bring an unprecedented decrease in the number of deaths reported during childbirth.

  20. Postnatal ontogeny of intestinal GCPII and the RFC in pig.

    PubMed

    Shafizadeh, Tracy B; Halsted, Charles H

    2009-03-01

    In humans and pigs, hydrolysis of dietary polyglutamyl folates is carried out by intestinal brush border folate hydrolase [glutamate carboxypeptidase II (GCPII)], whereas the transport of the monoglutamyl folate derivatives occurs via the intestinal brush border reduced folate carrier (RFC). The study objective was to measure the expression of intestinal GCPII and RFC during postnatal development of pigs and their effects on plasma and liver folate concentrations. Duodenum, jejunum, ileum, liver, and plasma samples were collected from female Yorkshire pigs at birth, 24 h, 1 wk, 3 wk, and 6 mo (n=6 at each time point). GCPII mRNA transcripts and protein (normalized using beta-actin), and enzyme activity (normalized per mg mucosal protein) were highest in all segments of small intestine at birth and were undetectable in ileum after 1 wk, whereas jejunal protein and activity predominated at 6 mo. RFC mRNA transcripts were present in all segments of small intestine at birth and declined significantly throughout development to 6 mo. Conversely, RFC protein increased twofold during the first 24 h and remained constant throughout development in all segments of small intestine. Liver RFC mRNA transcripts were detected at birth but were reduced by 6 mo. Liver folate concentration increased throughout postnatal development, whereas plasma folate levels increased during the first 24 h but decreased over time, reflecting the pattern of RFC expression in small intestine. These findings show that intestinal GCPII and intestinal and hepatic RFC all exhibit ontogenic changes in the pig that are reflected in postnatal folate status.

  1. [The organization of medical stomatological care of women in post-natal period].

    PubMed

    Kulikova, N G; Omeltchuk, N N; Zalenskiy, V A; Tkachenko, A S

    2014-01-01

    The article presents the following new data. The medical social aspects of women with stomatological pathology during post-natal period are characterized by age gender, professional, educational and organizational aspects. The issues of impact of characteristics of medical stomatological care of women in post-natal period are considered. The results of survey of women in post-natal period using questionnaire targeted to detection of stomatological diseases are presented.

  2. Mesenchymal hamartoma: prenatal and postnatal diagnosis by imaging.

    PubMed

    Martínez-Varea, Alicia; Vila-Vives, Jose María; Hidalgo-Mora, Juan José; Abad-Carrascosa, Antonio; Llorens-Salvador, Roberto; Perales-Marín, Alfredo

    2012-01-01

    We present a case of a twin pregnancy in which one fetus developed a rapidly growing unilateral intrathoracic tumor. While a cystic adenomatoid malformation was suspected in the ultrasound scan, the magnetic resonance scan suggested a pulmonary blastoma or a bronchioalveolar carcinoma. Postnatal chest radiography and contrast-enhanced computed tomography of the affected newborn were performed, and it was ruled out the possibility of malignant origin. Finally, the anatomopathologic exam revealed the presence of a mesenchymal hamartoma in the chest wall. Nevertheless, parents refused any treatment for the newborn.

  3. 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

  4. Postnatal reproductive autonomy: promoting relational autonomy and self-trust in new parents.

    PubMed

    Goering, Sara

    2009-01-01

    New parents suddenly come face to face with myriad issues that demand careful attention but appear in a context unlikely to provide opportunities for extended or clear-headed critical reflection, whether at home with a new baby or in the neonatal intensive care unit. As such, their capacity for autonomy may be compromised. Attending to new parental autonomy as an extension of reproductive autonomy, and as a complicated phenomenon in its own right rather than simply as a matter to be balanced against other autonomy rights, can help us to see how new parents might be aided in their quest for competency and good decision making. In this paper I show how a relational view of autonomy--attentive to the coercive effects of oppressive social norms and to the importance of developing autonomy competency, especially as related to self-trust--can improve our understanding of the situation of new parents and signal ways to cultivate and to better respect their autonomy.

  5. Postnatal depression among Sudanese women: prevalence and validation of the Edinburgh Postnatal Depression Scale at 3 months postpartum

    PubMed Central

    Khalifa, Dina Sami; Glavin, Kari; Bjertness, Espen; Lien, Lars

    2015-01-01

    Purpose Postnatal depression (PND) rates in low-resource countries have reached levels between 4.9% and 59%. Maternal mental health has not been researched in Sudan, and there are no existing statistics on prevalence or significant risk factors for PND. Consequently, no screening test has been validated to screen for PND at the primary health care level. This study investigates the 3 months prevalence of PND and validates the Edinburgh Postnatal Depression Scale (EPDS) against the Mini-International Neuropsychiatric Interview (MINI). Methodology Pregnant Sudanese women in the second and third trimesters were recruited to the study during routine antenatal care visits in two major maternity hospitals in Khartoum state. They were screened for PND at 3 months postpartum using the EPDS. Test positive women were matched with test negative women according to nearest date of birth. A clinical psychologist verified their depression status using the MINI. Results The follow-up rate was 79%. At a cutoff point of ≥12, the 3 months prevalence of PND was 9.2%. The sensitivity and specificity of the EPDS were 89% and 82%, respectively. The EPDS and MINI showed a strong positive relationship (odds ratio =36). The positive predictive value and negative predictive value, using this study’s prevalence, were 33% and 98.7%, respectively. The receiver operator characteristic analysis showed an area under the curve of 0.89. The cut-off point ≥12 was the most acceptable point as it had the lowest number needed to diagnose (1.4) and a false-positive rate of 18%. Conclusion The EPDS is a valid tool for screening for PND on a Sudanese population. It was accepted, easily administered, and understood by postnatal women. Health care personnel, especially village midwives, should be trained on screening and referral of depressed women for clinical evaluation and management. Due to limited resources available in Sudan, shorter screening tests need to be validated in the future. PMID

  6. Effects of Postnatal Estrogen Manipulations on Juvenile Alloparental Behavior

    PubMed Central

    Perry, Adam N.; Carter, C. Sue; Cushing, Bruce S.

    2015-01-01

    Sex- and species-specific patterns of estrogen receptor (ER)-α expression are established early in development, which may contribute to sexual differentiation of behavior and determine male social organization. The current study investigated the effects of ERα and ERβ activation during the second postnatal week on subsequent alloparental behavior and ERα expression in juvenile prairie voles. Male and female pups were treated daily with 17β-estradiol (E2, ERα/ERβ agonist), PPT (selective ERα agonist), DPN (selective ERβ agonist), or the oil vehicle on postnatal days (PD) 8-14. Alloparental behavior and ERα expression were examined at PD21. PPT treatment inhibited prosocial motivation in males and increased pup-directed aggression in both sexes. E2 and DPN had no apparent effect on behavior in either sex. PPT-treated males had increased ERα expression in the medial preoptic area (MPN), medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpr). DPN treatment also increased ERα expression in males, but only in the BSTpr. Female ERα expression was unaffected by treatment. These results support the hypothesis that ERα activation in early life is associated with less prosocial patterns of central ERα expression and alloparental behavior in males. The lack of an effect of E2 on behavior suggests that ERβ may antagonize the effects of ERα on alloparental behavior. The results in DPN-treated males suggest that ERα in the MEApd, and not the BSTpr, may be a primary determinant of alloparental behavior in males. PMID:26222494

  7. 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

  8. Developmental immunotoxicity (DIT), postnatal immune dysfunction and childhood leukemia.

    PubMed

    Dietert, Rodney R

    2009-01-01

    The developing immune system is a sensitive target for environmentally-induced disruption producing postnatal immune dysfunction. Unique immune maturational events occur during critical windows of prenatal/perinatal development and environmentally-induced disruption of one-time events can have serious health consequences. Additionally, the specialized immunological conditions necessary to bring a semi-allogeneic fetus to term place restrictions on both the maternal and offspring immune systems. These features combine not only to increase the risk of early-life immune insult (ELII), which includes xenobiotically-induced developmental immunotoxicity (DIT), but also to influence the nature of DIT-associated diseases for the child. Exposure to certain toxicants as well as maternal infections and other pregnancy stressors is known to induce postnatal immune dysfunction. Because dysfunctional immune responses to childhood infections have been proposed to play a role in childhood leukemia, DIT is a potential risk factor for this disease. This review details the range of disease susceptibilities impacted by DIT and discusses the importance of effective DIT safety testing for drugs and chemicals as a preventative measure.

  9. Advancing social research relationships in postnatal support settings.

    PubMed

    Tighe, Maria; Peters, Jane; Skirton, Heather

    2013-05-01

    Global trends in public health nursing (PHN) suggest the value of community-based social research. However, it is not always clear how social research relationships may be of benefit to PHN or how such skills can best be learned and applied. To advance this understanding, we present a qualitative analysis of the development of social research relationships in PHN. Using a background literature review as a foundation, our qualitative mixed method strategy involved a comparative case-study analysis based on the authors' participant observation in two distinct postnatal group settings. Our findings suggest that participant observation facilitates the advancement of social research relationships through practitioner-research management of role conflict. Reflexivity and reciprocity is an emergent relational process, which relies upon a de-professionalization of the traditional PHN role. Conversely, social research relationships help build PHN capacity for family health needs assessment. Thus, we contend that the application of participant observation enables the development of social research relationships, which advance the practice of PHN in postnatal support settings.

  10. 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.

  11. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    PubMed

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use.

  12. Postnatal changes in fatty acids composition of brown adipose tissue

    NASA Astrophysics Data System (ADS)

    Ohno, T.; Ogawa, K.; Kuroshima, A.

    1992-03-01

    It has been demonstrated that thermogenic activity of brown adipose tissue (BAT) is higher during the early postnatal period, decreasing towards a low adult level. The present study examined postnatal changes in the lipid composition of BAT. BAT from pre-weaning rats at 4 and 14 days old showed the following differences in lipid composition compared to that from adults of 12 weeks old. (i) Relative weight of interscapular BAT to body weight was markedly greater. (ii) BAT-triglyceride (TG) level was lower, while BAT-phospholipid (PL)level was higher. (iii) In TG fatty acids (FA) polyunsaturated fatty acids (PU; mol %), arachidonate index (AI), unsaturation index (UI) and PU/saturated FA (SA) were higher; rare FA such as eicosadienoate, bishomo- γ-linolenic acid and lignoceric acid in mol % were also higher. (iv) In PL-FA monounsaturated FA (MU) in mol % was lower; PU mol %, AI and UI were higher. These features in BAT of pre-weaning rats resembled those in the cold-acclimated adults, suggesting a close relationship of the PL-FA profile to high activity of BAT.

  13. The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

    SciTech Connect

    Chen Yanan; Tang, Bor Luen . E-mail: bchtbl@nus.edu.sg

    2006-03-03

    The amyloid precursor protein (APP) is the source of amyloid-beta (A{beta}) peptide, produced via its sequential cleavage {beta}- and {gamma}-secretases. Various biophysical forms of A{beta} (and the mutations of APP which results in their elevated levels) have been implicated in the etiology and early onset of Alzheimer's disease. APP's evolutionary conservation and the existence of APP-like isoforms (APLP1 and APLP2) which lack the A{beta} sequence, however, suggest that these might have important physiological functions that are unrelated to A{beta} production. Soluble N-terminal fragments of APP have been known to be neuroprotective, and the interaction of its cytoplasmic C-terminus with a myriad of proteins associates it with diverse processes such as axonal transport and transcriptional regulation. The notion for an essential postnatal function of APP has been demonstrated genetically, as mice deficient in both APP and APLP2 or all three APP isoforms exhibit early postnatal lethality and neuroanatomical abnormalities. Recent findings have also brought to light two possible functions of the APP family in Brain-regulation of neural progenitor cell proliferation and axonal outgrowth after injury. Interestingly, these two apparently related neurogenic/neuroregenerative functions of APP involve two separate domains of the molecule.

  14. Effects of postnatal estrogen manipulations on juvenile alloparental behavior.

    PubMed

    Perry, Adam N; Sue Carter, C; Cushing, Bruce S

    2015-09-01

    Sex- and species-specific patterns of estrogen receptor (ER)-α expression are established early in development, which may contribute to sexual differentiation of behavior and determine male social organization. The current study investigated the effects of ERα and ERβ activation during the second postnatal week on subsequent alloparental behavior and ERα expression in juvenile prairie voles. Male and female pups were treated daily with 17β-estradiol (E2, ERα/ERβ agonist), PPT (selective ERα agonist), DPN (selective ERβ agonist), or the oil vehicle on postnatal days (PD) 8-14. Alloparental behavior and ERα expression were examined at PD21. PPT treatment inhibited prosocial motivation in males and increased pup-directed aggression in both sexes. E2 and DPN had no apparent effect on behavior in either sex. PPT-treated males had increased ERα expression in the medial preoptic area (MPN), medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpr). DPN treatment also increased ERα expression in males, but only in the BSTpr. Female ERα expression was unaffected by treatment. These results support the hypothesis that ERα activation in early life is associated with less prosocial patterns of central ERα expression and alloparental behavior in males. The lack of an effect of E2 on behavior suggests that ERβ may antagonize the effects of ERα on alloparental behavior. The results in DPN-treated males suggest that ERα in the MEApd, and not the BSTpr, may be a primary determinant of alloparental behavior in males.

  15. 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.

  16. 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.

  17. Staffing in postnatal units: is it adequate for the provision of quality care? Staff perspectives from a state-wide review of postnatal care in Victoria, Australia

    PubMed Central

    Forster, Della A; McLachlan, Helen L; Yelland, Jane; Rayner, Jo; Lumley, Judith; Davey, Mary-Ann

    2006-01-01

    Background State-wide surveys of recent mothers conducted over the past decade in Victoria, one state of Australia, have identified that women are consistently less satisfied with the care they received in hospital following birth compared with other aspects of maternity care. Little is known of caregivers' perspectives on the provision ofhospital postnatal care: how care is organised and provided in different hospitals; what constrains the provision of postnatal care (apart from funding) and what initiatives are being undertaken to improve service delivery. A state-widereview of organisational structures and processes in relation to the provision of hospital postnatal care in Victoria was undertaken. This paper focuses on the impact of staffing issues on the provision of quality postnatal care from the perspective of care providers. Methods A study of care providers from Victorian public hospitals that provide maternity services was undertaken. Datawere collected in two stages. Stage one: a structured questionnaire was sent to all public hospitals in Victoria that provided postnatal care (n = 73), exploring the structure and organisation of care (e.g. staffing, routine observations, policy framework and discharge planning). Stage two: 14 maternity units were selected and invited to participate in a more in-depth exploration of postnatal care. Thirty-eight key informant interviews were undertaken with midwives (including unit managers, associate unit managers and clinical midwives) and a medical practitioner from eachselected hospital. Results Staffing was highlighted as a major factor impacting on the provision of quality postnatal care. There were significant issues associated with inadequate staff/patient ratios; staffing mix; patient mix; prioritisation of birth suites over postnatal units; and the use of non-permanent staff. Forty-three percent of hospitals reported having only midwives (i.e. no non-midwives) providing postnatal care. Staffing issues impact on

  18. A review of postnatal mental health websites: help for healthcare professionals and patients.

    PubMed

    Moore, Donna; Ayers, Susan

    2011-12-01

    The internet offers an accessible and cost-effective way to help women suffering with various types of postnatal mental illness and also can provide resources for healthcare professionals. Many websites on postnatal mental illness are available, but there is little information on the range or quality of information and resources offered. The current study therefore aimed to review postnatal health websites and evaluate their quality on a variety of dimensions. A systematic review of postnatal health websites was conducted. Searches were carried out on four search engines (Google, Yahoo, Ask Jeeves and Bing) which are used by 98% of web users. The first 25 websites found for each key word and their hyperlinks were assessed for inclusion in the review. Websites had to be exclusively dedicated to postnatal mental health or have substantial information on postnatal mental illness. Eligible websites (n=114) were evaluated for accuracy of information, available resources and quality. Results showed that information was largely incomplete and difficult to read; available help was limited and website quality was variable. The top five postnatal mental illness websites were identified for (1) postnatal mental illness sufferers and (2) healthcare professionals. It is hoped these top websites can be used by healthcare professionals both for their own information and to advise patients on quality online resources.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Effects of prenatal and postnatal fraternity size on long-term reproduction in mice.

    PubMed

    Kirkpatrick, B W; Arias, J A; Rutledge, J J

    1988-01-01

    Effects of prenatal and postnatal fraternity size (size of litter in which an animal develops prior to birth or is reared following birth) on long-term reproduction were studied by rearing 178 female ICR mice in standardized prenatal and postnatal fraternities. Three levels of prenatal and postnatal fraternity sizes were used in a 3 x 3 factorial experiment. Prenatal fraternity size was standardized by selectively terminating fetal development in pregnant females carrying at least 14 conceptuses. Prenatal fraternities were standardized to either 6, 10 or 14 fetuses, and postnatal fraternities were standardized by randomly assigning individuals to nurse litters of 5, 10 or 15 pups. Prenatal fraternity size negatively affected average pup weight at birth (P less than .05) but had little subsequent effect on growth or reproduction. Postnatal fraternity size negatively affected weight at weaning (P less than .01), with mice reared in smaller postnatal fraternities being heavier than those reared in larger fraternities. Following weaning, mice reared in smaller fraternities gained weight less rapidly (P less than .01) but still tended to be heavier at maturity (P = .11). Vaginal opening occurred at older ages in females reared in larger postnatal litters (P less than .01). An interval mating system was used to examine fraternity size effects on long-term reproduction. Females were exposed to males six times at 8-wk intervals with initial mating at 7 wk of age. Postnatal fraternity size and age at mating jointly affected litter size (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. The effects of prenatal and postnatal (via nursing) exposure to alcohol in rats

    SciTech Connect

    Nekvasil, N.; Baggio, C. )

    1992-02-26

    Pregnant and post-partum rats were given daily doses of 20% alcohol during days 13-21 gestation and postnatal days 3-12, respectively. Following exposure, all rat pups, were tested for balance, blood pressure, right and left cerebral hemisphere weights, and cerebellar weight. Results were grouped according to exposure and gender. The postnatal group was the only one to demonstrate difficulties with balance. The mean arterial pressure in males exposed postnatally was significantly lower than the control and prenatal males. Females exposed postnatally had a significantly higher blood pressure than control females. Within the postnatal group, males had a significantly lower blood pressure than the females. Prenatal and control females differed significantly for left cerebral hemisphere (LCH) weight with the prenatal weighing less. Male pups exposed prenatally had significantly heavier LCH than the postnatal and control males. For both males and females, postnatal LCH weights did not differ from those of the control pups. Within the prenatal group, the LCH weight in females was significantly lower than in males. Mean cerebellar weights were significantly lower in postnatal animals compared to control animals. A major finding of this study is that the effect of alcohol exposure on rat pups depends on gender and developmental age.

  2. A case of Norman-Roberts syndrome identified from postnatal diagnosis of microlissencephaly.

    PubMed

    Tosello, Barthélémy; Brévaut-Malaty, Véronique; Chaumoître, Kathia; Gire, Catherine

    2015-06-01

    Lissencephaly is a rare brain malformation. What differentiates microlissencephaly from classical lissencephaly and other variants is the presence of severe microcephaly. Very few postnatal cases of Norman-Roberts syndrome are described in the literature. We report a case of microlissencephaly with a polymalformative syndrome that prompted postnatal diagnosis of Norman-Roberts syndrome.

  3. Cultural variations in interpretation of postnatal illness: Jinn possession amongst Muslim communities.

    PubMed

    Hanely, Jane; Brown, Amy

    2014-04-01

    Maternal experience of emotional and physical disturbance during the postnatal period is a worldwide occurrence but may be interpreted differently according to cultural background. Little is known about different expressions and treatment of cultural phenomena during the postnatal period such as the affliction of Jinn possession in Arabic cultures. Jinn are considered to be evil spirits, which cause emotional and physical distress at times of vulnerability such as the postnatal period. The aim of this paper was to explore maternal experience of Jinn possession and draw parallels with Western interpretations of postnatal illness. Ten women in an Arabian Gulf state who had recently given birth and identified themselves as having Jinn possession were interviewed as to their experiences of Jinn possession. Mothers described the Jinn as evil spirits who cause symptoms such as sadness, anxiety and physical malaise during the postnatal period. Numerous risk factors for possession emerged such as lack of familial support, poverty and a traumatic birth. Clear parallels emerged between Western concepts of postnatal illness and Jinn possession. Mothers in Muslim cultures may experience Jinn possession during the postnatal period, which reflects similar symptoms and aetiology to Western concepts of postnatal illness. With increasing multiculturalism in the UK, understanding the origins and perception of Jinn possession is important for health professionals working in Muslim communities here.

  4. Maternal Postnatal Depression and the Development of Depression in Offspring up to 16 Years of Age

    ERIC Educational Resources Information Center

    Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Goodyer, Ian; Cooper, Peter

    2011-01-01

    Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702…

  5. Learning to breathe: habituation of Hering-Breuer inflation reflex emerges with postnatal brainstem maturation.

    PubMed

    Dutschmann, Mathias; Bautista, Tara G; Mörschel, Michael; Dick, Thomas E

    2014-05-01

    The Hering-Breuer (HBR) reflex is considered a major regulatory feedback for the generation and patterning of respiratory activity. While HBR is important in neonates, its significance in adults is controversial. Previous experiments that investigated the plasticity of entrainment of the respiratory rhythm by vagal input demonstrated postnatal changes in HBR plasticity. Here we analyzed postnatal changes in the plasticity of HBR by mimicking the classic lung inflation tests with repetitive tonic vagal stimulation across different postnatal stages in an in situ perfused brainstem preparation of rat. The study shows that neonates stereotypically exhibit HBR stimulus-dependent prolongation of expiration while juvenile preparations (>postnatal day 16) showed significant habituation of HBR following repetitive stimulation. Subsequent experiments employing physiological lung inflation tests in situ confirmed HBR habituation in juveniles. We conclude that postnatal emergence of HBR habituation explains the weak contribution and high activation threshold of HBR in the regulation of eupnea.

  6. Post-natal growth in the rat pineal gland: a stereological study.

    PubMed

    Erbagci, H; Kizilkan, N; Ozbag, D; Erkilic, S; Kervancioglu, P; Canan, S; Gumusburun, E

    2012-10-01

    The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies.

  7. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response.

    PubMed

    Puente, Bao N; Kimura, Wataru; Muralidhar, Shalini A; Moon, Jesung; Amatruda, James F; Phelps, Kate L; Grinsfelder, David; Rothermel, Beverly A; Chen, Rui; Garcia, Joseph A; Santos, Celio X; Thet, SuWannee; Mori, Eiichiro; Kinter, Michael T; Rindler, Paul M; Zacchigna, Serena; Mukherjee, Shibani; Chen, David J; Mahmoud, Ahmed I; Giacca, Mauro; Rabinovitch, Peter S; Aroumougame, Asaithamby; Shah, Ajay M; Szweda, Luke I; Sadek, Hesham A

    2014-04-24

    The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary postnatal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen-rich postnatal environment is the upstream signal that results in cell-cycle arrest of cardiomyocytes. Here, we show that reactive oxygen species (ROS), oxidative DNA damage, and DNA damage response (DDR) markers significantly increase in the heart during the first postnatal week. Intriguingly, postnatal hypoxemia, ROS scavenging, or inhibition of DDR all prolong the postnatal proliferative window of cardiomyocytes, whereas hyperoxemia and ROS generators shorten it. These findings uncover a protective mechanism that mediates cardiomyocyte cell-cycle arrest in exchange for utilization of oxygen-dependent aerobic metabolism. Reduction of mitochondrial-dependent oxidative stress should be an important component of cardiomyocyte proliferation-based therapeutic approaches.

  8. p38α MAPK regulates adult muscle stem cell fate by restricting progenitor proliferation during postnatal growth and repair.

    PubMed

    Brien, Patrick; Pugazhendhi, Dhamayanthi; Woodhouse, Samuel; Oxley, David; Pell, Jennifer M

    2013-08-01

    Stem cell function is essential for the maintenance of adult tissue homeostasis. Controlling the balance between self-renewal and differentiation is crucial to maintain a receptive satellite cell pool capable of responding to growth and regeneration cues. The mitogen-activated protein kinase p38α has been implicated in the regulation of these processes but its influence in adult muscle remains unknown. Using conditional satellite cell p38α knockout mice we have demonstrated that p38α restricts excess proliferation in the postnatal growth phase while promoting timely myoblast differentiation. Differentiation was still able to occur in the p38α-null satellite cells, however, but was delayed. An absence of p38α resulted in a postnatal growth defect along with the persistence of an increased reservoir of satellite cells into adulthood. This population was still capable of responding to cardiotoxin-induced injury, resulting in complete, albeit delayed, regeneration, with further enhancement of the satellite cell population. Increased p38γ phosphorylation accompanied the absence of p38α, and inhibition of p38γ ex vivo substantially decreased the myogenic defect. We have used genome-wide transcriptome analysis to characterize the changes in expression that occur between resting and regenerating muscle, and the influence p38α has on these expression profiles. This study provides novel evidence for the fundamental role of p38α in adult muscle homeostasis in vivo.

  9. Lin41/Trim71 is essential for mouse development and specifically expressed in postnatal ependymal cells of the brain.

    PubMed

    Cuevas, Elisa; Rybak-Wolf, Agnieszka; Rohde, Anna M; Nguyen, Duong T T; Wulczyn, F Gregory

    2015-01-01

    Lin41/Trim71 is a heterochronic gene encoding a member of the Trim-NHL protein family, and is the original, genetically defined target of the microRNA let-7 in C. elegans. Both the LIN41 protein and multiple regulatory microRNA binding sites in the 3' UTR of the mRNA are highly conserved from nematodes to humans. Functional studies have described essential roles for mouse LIN41 in embryonic stem cells, cellular reprogramming and the timing of embryonic neurogenesis. We have used a new gene trap mouse line deficient in Lin41 to characterize Lin41 expression during embryonic development and in the postnatal central nervous system (CNS). In the embryo, Lin41 is required for embryonic viability and neural tube closure. Nevertheless, neurosphere assays suggest that Lin41 is not required for adult neurogenesis. Instead, we show that Lin41 promoter activity and protein expression in the postnatal CNS is restricted to ependymal cells lining the walls of the four ventricles. We use ependymal cell culture to confirm reestablishment of Lin41 expression during differentiation of ependymal progenitors to post-mitotic cells possessing motile cilia. Our results reveal that terminally differentiated ependymal cells express Lin41, a gene to date associated with self-renewing stem cells.

  10. Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids.

    PubMed

    Tam, Emily W Y; Chau, Vann; Ferriero, Donna M; Barkovich, A James; Poskitt, Kenneth J; Studholme, Colin; Fok, Eric D-Y; Grunau, Ruth E; Glidden, David V; Miller, Steven P

    2011-10-19

    As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

  11. Isolation of neural stem cells from the postnatal cerebellum.

    PubMed

    Lee, Audra; Kessler, Jessica D; Read, Tracy-Ann; Kaiser, Constanze; Corbeil, Denis; Huttner, Wieland B; Johnson, Jane E; Wechsler-Reya, Robert J

    2005-06-01

    The cerebellum is critical for motor coordination and cognitive function and is the target of transformation in medulloblastoma, the most common malignant brain tumor in children. Although the development of granule cells, the most abundant neurons in the cerebellum, has been studied in detail, the origins of other cerebellar neurons and glia remain poorly understood. Here we show that the murine postnatal cerebellum contains multipotent neural stem cells (NSCs). These cells can be prospectively isolated based on their expression of the NSC marker prominin-1 (CD133) and their lack of markers of neuronal and glial lineages (lin-). Purified prominin+ lin- cells form self-renewing neurospheres and can differentiate into astrocytes, oligodendrocytes and neurons in vitro. Moreover, they can generate each of these lineages after transplantation into the cerebellum. Identification of cerebellar stem cells has important implications for the understanding of cerebellar development and the origins of medulloblastoma.

  12. 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.

  13. Roles of MicroRNA across Prenatal and Postnatal Periods

    PubMed Central

    Floris, Ilaria; Kraft, Jamie D.; Altosaar, Illimar

    2016-01-01

    Communication between mother and offspring in mammals starts at implantation via the maternal–placental–fetal axis, and continues postpartum via milk targeted to the intestinal mucosa. MicroRNAs (miRNAs), short, noncoding single-stranded RNAs, of about 22 nucleotides in length, are actively involved in many developmental and physiological processes. Here we highlight the role of miRNA in the dynamic signaling that guides infant development, starting from implantation of conceptus and persisting through the prenatal and postnatal periods. miRNAs in body fluids, particularly in amniotic fluid, umbilical cord blood, and breast milk may offer new opportunities to investigate physiological and/or pathological molecular mechanisms that portend to open novel research avenues for the identification of noninvasive biomarkers. PMID:27916805

  14. 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).

  15. Pre- and postnatal findings in trisomy 17 mosaicism.

    PubMed

    Utermann, Barbara; Riegel, Mariluce; Leistritz, Dru; Karall, Thomas; Wisser, Josef; Meisner, Lorraine; Fauth, Christine; Baldinger, Rosa; Johnson, Julie; Erdel, Martin; Taralczak, Malgorzata; Pauli, Richard M; Baumer, Alessandra; Schinzel, Albert; Kotzot, Dieter

    2006-08-01

    Trisomy 17 mosaicism is one of the rarest autosomal trisomies in humans. Thus far, only 23 cases have been described, most of them detected prenatally. In only five instances has mosaicism been demonstrated in lymphocytes and/or fibroblasts postnatally, and only in these have multiple congenital anomalies (MCA), facial dysmorphisms, and mental retardation been reported. Patients with trisomy 17 mosaicism at amniocentesis and a normal karyotype in blood and fibroblasts (n = 17) were always healthy. Here, we report on pre- and postnatal clinical, cytogenetic, molecular-cytogenetic, and molecular findings in four patients with trisomy 17 mosaicism. The first case was detected in cultured but not in short-term chorionic villi and amniocytes. Due to MCA on prenatal ultrasound examination the pregnancy was terminated. The second patient is a 13-month-old healthy boy, in whom low level trisomy 17 mosaicism was detected in cultured chorionic villi only. The third patient is a 2-year-old girl with growth retardation, developmental delay, MCA, and trisomy 17 mosaicism in amniocytes, fibroblasts, and placenta, but not in blood and buccal smear. The fourth patient is a 9-year-old boy with growth and mental retardation, sensoneurinal hearing loss, and MCA. Cytogenetic analyses showed trisomy 17 mosaicism in amniocytes, skin fibroblasts, and urinary sediment cells, whereas in blood and buccal smear a 46,XY karyotype was found. Molecular investigations in all four cases indicated biparental inheritance of chromosome 17. Formation of trisomy was most likely due to a maternal meiosis I error in Patient 1 and a postzygotic non-disjunction of the paternal chromosome 17 in Patient 4. Cerebellar malformations, reported in two cases from the literature and in two reported here may be a specific feature of trisomy 17 mosaicism. Since the aberration has rarely been reported in lymphocytes, chordocentesis is not indicated in prenatal diagnosis. Prenatal genetic counseling for trisomy 17

  16. Feasibility and acceptability of alternate methods of postnatal data collection.

    PubMed

    McCormack, Lacey A; Friedrich, Christa; Fahrenwald, Nancy; Specker, Bonny

    2014-05-01

    This study was done in preparation for the launch of the National Children's Study (NCS) main study. The goal of this study was to examine the feasibility (completion rates and completeness of data), acceptability, staff time and cost-effectiveness of three methods of data collection for the postnatal 3- and 9-month questionnaires completed as part of NCS protocol. Eligible NCS participants who were scheduled to complete a postnatal questionnaire at three and nine months were randomly assigned to receive either: (a) telephone data collection (b) web-based data collection, or (c) self-administered (mailed) questionnaires. Event completion rates and satisfaction across the three data collection methods were compared and the influence of socio-demographic factors on completion rates and satisfaction rates was examined. Cost data were compared to data for completion and satisfaction for each of the delivery methods. Completion rates and satisfaction did not differ significantly by method, but completeness of data did, with odds of data completeness higher among web than phone (p < 0.001) or mail (p < 0.001). Costs were highest for the phone, followed by mail and web methods (p < 0.001). No significant differences in participant time (i.e. burden) across the three data collection methods were seen. Mail and phone data collection were the least complete of the three methods and were the most expensive. Mailed data collection was neither complete nor exceptionally economical. Web-based data collection was the least costly and provided the most complete data. Participants without web access could complete the questionnaire over the phone.

  17. 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.

  18. Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus

    PubMed Central

    Breunig, Joshua J.; Silbereis, John; Vaccarino, Flora M.; Šestan, Nenad; Rakic, Pasko

    2007-01-01

    The lifelong addition of neurons to the hippocampus is a remarkable form of structural plasticity, yet the molecular controls over proliferation, neuronal fate determination, survival, and maturation are poorly understood. Expression of Notch1 was found to change dynamically depending on the differentiation state of neural precursor cells. Through the use of inducible gain- and loss-of-function of Notch1 mice we show that this membrane receptor is essential to these distinct processes. We found in vivo that activated Notch1 overexpression induces proliferation, whereas γ-secretase inhibition or genetic ablation of Notch1 promotes cell cycle exit, indicating that the level of activated Notch1 regulates the magnitude of neurogenesis from postnatal progenitor cells. Abrogation of Notch signaling in vivo or in vitro leads to a transition from neural stem or precursor cells to transit-amplifying cells or neurons. Further, genetic Notch1 manipulation modulates survival and dendritic morphology of newborn granule cells. These results provide evidence for the expansive prevalence of Notch signaling in hippocampal morphogenesis and plasticity, suggesting that Notch1 could be a target of diverse traumatic and environmental modulators of adult neurogenesis. PMID:18077357

  19. Heart-specific expression of FGF-16 and a potential role in postnatal cardioprotection.

    PubMed

    Wang, Jie; Sontag, David; Cattini, Peter A

    2015-02-01

    Fibroblast growth factor 16 (FGF-16) was originally cloned from rat heart. Subsequent investigation of mouse FGF-16, including generation of null mice, revealed a specific pattern of expression in the endocardium and epicardium, and role for FGF-16 during embryonic heart development. FGF-16 is expressed mainly in brown adipose tissue during rat embryonic development, but is expressed mainly in the murine heart after birth. There is also an apparent switch from limited endocardial and epicardial expression in the embryo to the myocardium in the perinatal period. The FGF-16 gene and its location on the X chromosome are conserved between human and murine species, and no other member of the FGF family shows this pattern of spatial and temporal expression. The human and murine FGF-16 gene promoter regions also share an equivalent location for TATA sequences, as well as adjacent putative binding sites for transcription factors linked to cardiac expression and response to stress. Recent evidence has implicated nonsense mutation of FGF-16 with increased cardiovascular risk, and FGF-16 supplementation with cardioprotection. Here we review the important role of FGF-16 in embryonic heart development, its gene regulation, and evidence for FGF-16 as an endogenous and exogenous cardiac-specific and protective factor in the postnatal heart. Moreover, given the conservation of the FGF-16 gene and its chromosomal location between species, the question of support for a cardiac role in the human population is also considered.

  20. Delay of Postnatal Maturation Sensitizes the Mouse Prostate to Testosterone-Induced Pronounced Hyperplasia

    PubMed Central

    Savolainen, Saija; Pakarainen, Tomi; Huhtaniemi, Ilpo; Poutanen, Matti; Mäkelä, Sari

    2007-01-01

    The role of estrogens in the etiology of prostate cancer is controversial. To demonstrate the specific effects of estrogens and androgens on the development of the prostatic epithelial hyperplasia, we used luteinizing hormone receptor knockout mice (LuRKO), which are resistant to pituitary regulation mediated by luteinizing hormone, lack postnatal androgen production, and have rudimentary accessory sex glands, the growth of which can be induced with exogenous androgen replacement. This model is thus ideal for the investigation of direct hormonal effects on the prostate. Testosterone, but not 5α-dihydrotestosterone, replacement from 21 days of life for 8 weeks induced pronounced hyperplasia and inflammation in the prostates of LuRKO mice. Interestingly, 5α-dihydrotestosterone combined with 17β-estradiol did not induce hyperplasia or inflammation, and treatments with inhibitors of estrogen action, aromatase inhibitor, and ICI 182780 further exacerbated testosterone-induced hyperplastic growth. However, the activation of estrogen receptor (ER)-β with a specific agonist, DPN [2,3-bis(4-hydroxyphenol)-propionitrile], prevented the development of prostatic hyperplasia and inflammation in testosterone-treated LuRKO mice. Thus, it seems that in the presence of sufficient androgenic stimulation, it is the balance between ER-α- and ER-β-mediated signaling that determines whether estrogens promote hyperplasia or protect the prostate against hyperplastic changes. PMID:17640960

  1. Maternal Postnatal Depression and Anxiety and Their Association with Child Emotional Negativity and Behavior Problems at Two Years

    ERIC Educational Resources Information Center

    Prenoveau, Jason M.; Craske, Michelle G.; West, Valerie; Giannakakis, Andreas; Zioga, Maria; Lehtonen, Annukka; Davies, Beverley; Netsi, Elena; Cardy, Jessica; Cooper, Peter; Murray, Lynne; Stein, Alan

    2017-01-01

    Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major…

  2. 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.

  3. 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.

  4. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice

    PubMed Central

    Neuhold, Lisa A.; Killar, Loran; Zhao, Weiguang; Sung, Mei-Li A.; Warner, Linda; Kulik, John; Turner, James; Wu, William; Billinghurst, C.; Meijers, T.; Poole, A. Robin; Babij, Philip; DeGennaro, Louis J.

    2001-01-01

    It has been suggested that increased collagenase-3 (MMP-13) activity plays a pivotal role in the pathogenesis of osteoarthritis (OA). We have used tetracycline-regulated transcription in conjunction with a cartilage-specific promoter to target a constitutively active human MMP-13 to the hyaline cartilages and joints of transgenic mice. Postnatal expression of this transgene resulted in pathological changes in articular cartilage of the mouse joints similar to those observed in human OA. These included characteristic erosion of the articular cartilage associated with loss of proteoglycan and excessive cleavage of type II collagen by collagenase, as well as synovial hyperplasia. These results demonstrate that excessive MMP-13 activity can result in articular cartilage degradation and joint pathology of the kind observed in OA, suggesting that excessive activity of this proteinase can lead to this disease. PMID:11134178

  5. 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.

  6. Identification of proliferative progenitors associated with prominent postnatal growth of the pons

    PubMed Central

    Lindquist, Robert A.; Guinto, Cristina D.; Rodas-Rodriguez, Jose L.; Fuentealba, Luis C.; Tate, Matthew C.; Rowitch, David H.; Alvarez-Buylla, Arturo

    2016-01-01

    The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0–4 (P0–P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2+Olig2+, but by P8 a Sox2− subpopulation emerges, suggesting a lineage progression from Sox2+ ‘early' to Sox2− ‘late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2–P3 Sox2+ progenitors. These results demonstrate the importance of postnatal Sox2+Olig2+ progenitors in pontine growth and oligodendrogenesis. PMID:27188978

  7. Cognitive behaviour therapy for postnatal post-traumatic stress disorder: case studies.

    PubMed

    Ayers, Susan; McKenzie-McHarg, Kirstie; Eagle, Andrew

    2007-09-01

    Background. Approximately 1-2% of women suffer from postnatal post-traumatic stress disorder (PTSD) with wide ranging consequences for these women and their families 1. Appropriate treatment of women who have difficult or traumatic births is not yet established. Evidence in other populations shows that cognitive behavior therapy (CBT) is effective for PTSD and it is therefore the recommended treatment 2. However, a recent review of treatments for postnatal distress concluded that descriptions of postnatal counseling are largely generalized and non-specific, which makes them difficult to assess or replicate 3. Aims and method. The current paper therefore aims to describe the use of CBT interventions to treat postnatal distress, and to illustrate common themes or issues that occur in postnatal PTSD. This paper reports two case studies of women with postnatal PTSD and their treatment using CBT. Conclusions. In these cases, CBT was an effective treatment for postnatal PTSD. A number of implications are explored for the management of pregnancy and labor.

  8. Neuroendocrine responses to social isolation and paternal deprivation at different postnatal ages in Mandarin voles.

    PubMed

    Wang, Lu; Zhang, Wei; Wu, Ruiyong; Kong, Lingzhe; Feng, Weige; Cao, Yan; Tai, Fadao; Zhang, Xia

    2014-09-01

    Neonatal isolation and paternal deprivation have long lasting effects on the behavior and neuroendocrine system at adulthood. Whether these effects at adulthood are induced by neonatal changes in relevant neuroendocrine parameters lead by these early-life social experiences is not well understood. Whether monogamous rodents exhibit a stress hypo-responsive period (SHRP) also remains unclear. Using the monogamous mandarin vole, we found that 30 min of isolation did not affect levels of corticosterone (CORT) and adrenocorticotropin (ACTH) at postnatal days 8, 10, and 12 displaying a SHRP, but increased these at postnatal days 4, 14, 16, and 18. Isolation increased vasopressin (AVP)-ir neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) from postnatal days 4 to 12, and up-regulated oxytocin (OT)-ir neurons in the PVN at postnatal days 4 and 8 and SON at postnatal day 4. Paternally deprived pups showed increase in ACTH and CORT after 30 min of social isolation from postnatal days 8 to 14, increase in AVP-ir neurons in the PVN from postnatal days 10 to 14, reduction in OT-ir neurons in the PVN from postnatal days 10 to 14 and in the SON at postnatal days 12 and 14. These results indicate that monogamous mandarin voles display a short SHRP which can be disrupted by paternal deprivation. Central AVP and OT levels may also be altered by paternal deprivation and social isolation. We propose that changes in these neuroendocrine parameters induced by early-life social experiences such as those tested here persist and result.

  9. Postnatal experience and health needs of Chinese migrant women in Brisbane, Australia.

    PubMed

    Chu, Cordia M Y

    2005-02-01

    In Chinese society, traditional postnatal practices and family support protect the health and well-being of women after childbirth. The absence of support for these practices for Chinese migrants in Western societies can have negative implications for their health. Recent studies reveal that postnatal stress is a growing concern among Chinese migrant women in Brisbane, Australia. There is a need to investigate the experiences of these women in order to understand factors affecting their postnatal health and to identify gaps in, and ways to improve, existing services and support identified needs. This paper examines postnatal experience and health needs of Chinese migrant women in Brisbane from three different places of origin: Taiwan, Hong Kong and the People's Republic of China (PRC). Previous studies on reproductive health beliefs and practices of Chinese women have found that a relationship exists between postnatal maternal health and postnatal cultural practices, appropriate family and community support and social circumstances, particularly pressures relating to employment. This study further tests and confirms these findings by comparing the experience of the three Chinese groups who have different migration circumstances, socio-economic and employment status, and support networks. The study reveals that among the three groups, PRC migrants are more likely to have encountered downward social mobility, economic hardship, social isolation, employment and language problems. While all three groups believe in the necessity of traditional postnatal practices, the PRC group has less support and is also more likely to have experienced postnatal health problems than the other two groups. This paper concludes with two sets of recommendations: one for community organizations with a focus on empowerment and cooperation; and one for service providers concerning improvement of multi-sectoral partnership, cross-cultural communication and the development of a postnatal care

  10. 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.

  11. 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.

  12. The postnatal growth of motoneurons at three levels of the cat neuraxis.

    PubMed

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

    1989-10-09

    The postnatal growth of motoneuron cell bodies located in the brainstem, cervical and lumbosacral spinal cord was investigated using retrograde transport of horseradish peroxidase in kittens ages 2, 12, 30, 55, 82 and 114 postnatal days and in an adult. The motoneurons innervating an extrinsic tongue muscle, the genioglossus, reached their adult size by eight weeks after birth. In contrast, the phrenic motoneurons innervating the diaphragm achieved adult size by 12 weeks and the motoneurons innervating the medial gastrocnemius muscle continued to grow beyond the twelfth postnatal week. The sizes of these motoneurons relative to one another remained constant during periods of development.

  13. Between stigma and mother-blame: blind mothers' experiences in USA hospital postnatal care.

    PubMed

    Frederick, Angela

    2015-11-01

    This study examines instances of discrimination that blind mothers in the USA have experienced at the hands of doctors, nurses and social workers during hospital postnatal care. The author identifies postnatal care as the time when blind mothers are likely to face the most stigmatising interactions with medical staff, as it is when scepticism about their competence as mothers is at its height. The author argues these interactions must be understood within their institutional context in which ideologies of risk and mother-blame are embedded in hospital postnatal practices.

  14. 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.

  15. 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

  16. 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

  17. Postnatal neurophysiologic effects of prenatal X-irradiation.

    PubMed

    Jensh, R P; Eisenman, L M; Brent, R L

    1995-02-01

    Histological and neurophysiological effects of in utero irradiation were examined following exposure of pregnant Wistar rat to 2.0 Gy X-irradiation or sham-irradiated on the 17th day of gestation. The 234 newborns were monitored for the age of appearance of four selected physiologic markers and the age of acquisition of five selected reflexes. Offspring were evaluated as young adults using selected behavioural tests. Postnatal growth was monitored weekly. Selected offspring were autopsied to determine the presence of morphologic central nervous system alterations. The results indicated that 2.0 Gy X-irradiation during the foetal period in rat gestation caused permanent alterations in the mature adult organism, which include non-recuperable growth retardation, morphologic changes in the brain such as microcephaly, abnormal cerebellar cortical cellular patterns, and alterations in the cell architecture of the hippocampus; diminished attainment of selected reflexes; alterations in the appearance of selected physiologic markers; and changes in adult test performance indicating significant hyperactivity among the irradiated offspring. Such exposure to X-irradiation during this period results in behavioural and morphologic alterations, which persist throughout life.

  18. 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.

  19. 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.

  20. Cobalt-Induced Ototoxicity in Rat Postnatal Cochlear Organotypic Cultures.

    PubMed

    Li, Peng; Ding, Dalian; Salvi, Richard; Roth, Jerome A

    2015-10-01

    Cobalt (Co) is a required divalent metal used in the production of metal alloys, batteries, and pigments and is a component of vitamin B12. Excessive uptake of Co is neurotoxic causing temporary or permanent hearing loss; however, its ototoxic effects on the sensory hair cells, neurons, and support cells in the cochlea are poorly understood. Accordingly, we treated postnatal day 3 rat cochlear organotypic cultures with various doses and durations of CoCl2 and quantified the damage to the hair cells, peripheral auditory nerve fibers, and spiral ganglion neurons (SGN). Five-day treatment with 250 μM CoCl2 caused extensive damage to hair cells and neurons which increased with dose and treatment duration. CoCl2 caused greater damage to outer hair cells than inner hair cells; damage was greatest in the base of the cochlea and decreased towards the base. CoCl2 increased expression of superoxide radical in hair cells and SGNs and SGN loss was characterized by nuclear condensation and fragmentation, morphological features of apoptosis. CoCl2 treatment increased the expression of caspase-3 indicative of caspase-mediated programmed cell death. These results identify hair cells and spiral ganglion neurons as the main targets of Co ototoxicity in vitro and implicate the superoxide radical as a trigger of caspase-mediated ototoxicity.

  1. Reprogramming Postnatal Human Epidermal Keratinocytes toward Functional Neural Crest Fates.

    PubMed

    Bajpai, Vivek K; Kerosuo, Laura; Tseropoulos, Georgios; Cummings, Kirstie A; Wang, Xiaoyan; Lei, Pedro; Liu, Biao; Liu, Song; Popescu, Gabriela; Bronner, Marianne E; Andreadis, Stelios T

    2017-01-31

    During development, neural crest cells are induced by signaling events at the neural plate border of all vertebrate embryos. Initially arising within the central nervous system, neural crest cells subsequently undergo an epithelial to mesenchymal transition to migrate into the periphery, where they differentiate into diverse cell types. Here we provide evidence that postnatal human epidermal keratinocytes, in response to FGF2 and IGF1 signals, can be reprogrammed toward a neural crest fate. Genome-wide transcriptome analyses show that keratinocyte-derived neural crest cells are similar to those derived from human embryonic stem cells. Moreover, they give rise in vitro and in vivo to neural crest derivatives such as peripheral neurons, melanocytes, Schwann cells and mesenchymal cells (osteocytes, chondrocytes, adipocytes and smooth muscle). By demonstrating that human KRT14+ keratinocytes can form neural crest cells, even from clones of single cells, our results have important implications in stem cell biology and regenerative medicine. This article is protected by copyright. All rights reserved.

  2. Explaining postnatal growth plasticity in a generalist brood parasite

    NASA Astrophysics Data System (ADS)

    Remeš, Vladimír

    2010-03-01

    Selection of a particular host has clear consequences for the performance of avian brood parasites. Experimental studies showed that growth rate and fledging mass of brood parasites varied between host species independently of the original host species. Finding correlates of this phenotypic plasticity in growth is important for assessing adaptiveness and potential fitness consequences of host choice. Here, I analyzed the effects of several host characteristics on growth rate and fledging mass of the young of brown-headed cowbird ( Molothrus ater), a generalist, non-evicting brood parasite. Cowbird chicks grew better in fast-developing host species and reached higher fledging mass in large hosts with fast postnatal development. A potential proximate mechanism linking fast growth and high fledging mass of cowbird with fast host development is superior food supply in fast-developing foster species. So far, we know very little about the consequences of the great plasticity in cowbird growth for later performance of the adult parasite. Thus, cowbird species could become interesting model systems for investigating the role of plasticity and optimization in the evolution of growth rate in birds.

  3. 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.

  4. Rett syndrome: disruption of epigenetic control of postnatal neurological functions.

    PubMed

    Pohodich, Amy E; Zoghbi, Huda Y

    2015-10-15

    Loss-of-function mutations in the X-linked gene Methyl-CpG-binding protein 2 (MECP2) cause a devastating pediatric neurological disorder called Rett syndrome. In males, these mutations typically result in severe neonatal encephalopathy and early lethality. On the other hand, owing to expression of the normal allele in ∼50% of cells, females do not suffer encephalopathy but instead develop Rett syndrome. Typically females with Rett syndrome exhibit a delayed onset of neurologic dysfunction that manifests around the child's first birthday and progresses over the next few years. Features of this disorder include loss of acquired language and motor skills, intellectual impairment and hand stereotypies. The developmental regression observed in patients with Rett syndrome arises from altered neuronal function and is not the result of neurodegeneration. Maintenance of an appropriate level of MeCP2 appears integral to the function of healthy neurons as patients with increased levels of MeCP2, owing to duplication of the Xq28 region encompassing the MECP2 locus, also present with intellectual disability and progressive neurologic symptoms. Despite major efforts over the past two decades to elucidate the molecular functions of MeCP2, the mechanisms underlying the delayed appearance of symptoms remain unclear. In this review, we will highlight recent findings that have expanded our knowledge of MeCP2's functions, and we will discuss how epigenetic regulation, chromatin organization and circuit dynamics may contribute to the postnatal onset of Rett syndrome.

  5. 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

  6. Postnatal Foot Length to Determine Gestational Age: A Pilot Study.

    PubMed

    Wyk, Lizelle Van; Smith, Johan

    2016-04-01

    Gestational age is a critical factor in the management, decision-making, prognostication and follow-up of newborn infants. It is also essential for research and epidemiology. In the absence of an early assessment of fetal gestation by abdominal ultrasound, many neonatal units in developing countries determine gestational age by neonatal scores and last menstrual period-both of which are highly inaccurate. The aim of this pilot study was to determine whether postnatal foot length measurement could accurately determine gestational age in a specified South African hospitalized neonatal population. Foot length was measured with a plastic Verniere's caliper. Foot length was shown to correlate well with gestational age (r = 0.919,p < 0.001). Intra-observer and inter-observer variability of foot length measurements was low. Foot length can therefore be used with high accuracy to determine the gestational age in a population where there is poor access to or utilization of antenatal sonar.

  7. 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)

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 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

  10. Transcriptome Dynamics and Potential Roles of Sox6 in the Postnatal Heart

    PubMed Central

    Peng, Jie; Sinha, Neelima R.; Hagiwara, Nobuko

    2016-01-01

    The postnatal heart undergoes highly coordinated developmental processes culminating in the complex physiologic properties of the adult heart. The molecular mechanisms of postnatal heart development remain largely unexplored despite their important clinical implications. To gain an integrated view of the dynamic changes in gene expression during postnatal heart development at the organ level, time-series transcriptome analyses of the postnatal hearts of neonatal through adult mice (P1, P7, P14, P30, and P60) were performed using a newly developed bioinformatics pipeline. We identified functional gene clusters by principal component analysis with self-organizing map clustering which revealed organized, discrete gene expression patterns corresponding to biological functions associated with the neonatal, juvenile and adult stages of postnatal heart development. Using weighted gene co-expression network analysis with bootstrap inference for each of these functional gene clusters, highly robust hub genes were identified which likely play key roles in regulating expression of co-expressed, functionally linked genes. Additionally, motivated by the role of the transcription factor Sox6 in the functional maturation of skeletal muscle, the role of Sox6 in the postnatal maturation of cardiac muscle was investigated. Differentially expressed transcriptome analyses between Sox6 knockout (KO) and control hearts uncovered significant upregulation of genes involved in cell proliferation at postnatal day 7 (P7) in the Sox6 KO heart. This result was validated by detecting mitotically active cells in the P7 Sox6 KO heart. The current report provides a framework for the complex molecular processes of postnatal heart development, thus enabling systematic dissection of the developmental regression observed in the stressed and failing adult heart. PMID:27832192

  11. Antenatal anxiety disorder as a predictor of postnatal depression: a longitudinal study.

    PubMed

    Coelho, Helen F; Murray, Lynne; Royal-Lawson, Melanie; Cooper, Peter J

    2011-03-01

    Previous research has implicated high levels of antenatal anxiety as a predictor of postnatal depression, but there is a paucity of evidence on the relationship between the various forms of anxiety and postnatal depression. A longitudinal study of 246 mothers (56 with antenatal generalised anxiety disorder (GAD), 68 with antenatal generalised social phobia, 28 with both disorders in the antenatal period, and 94 with no antenatal GAD or social phobia) allowed us to explore whether antenatal social phobia and GAD predict high Edinburgh Postnatal Depression Scale (EPDS) scores (probable depression >12) at 10-14 days, 10-12 weeks, 10 months, 14 months, and 24 months postnatally. We found that, after accounting for the presence of other antenatal anxiety disorders, antenatal depression, maternal age at child's birth, socio-economic status and ethnicity in the models, antenatal GAD independently predicted depression at all time points after delivery. A less robust relationship was found for antenatal social phobia, which predicted postnatal depression at only 10 months after birth. One possibility consistent with our findings is that there may be differences in the timing of postnatal depression with different forms of antenatal anxiety disorders.

  12. 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.

  13. Health Promotion

    DTIC Science & Technology

    1986-03-11

    Department of Defense DIRECTIVEAD-A269 638 , , AD-A29 638March 11, 1986 IIIIii!IN 111111111,11 Ii1111,111111[NUMBER 1010.10 SUBJECT: Health Promotion ...34 March 13, 1985 INC A. URPOSE SThis Directive establishes a health promotion policy within the Department of Defense to improve and maintain military...civilian employees. C. DEFINITIONS 1. Health Promotion . Any combination of health education and related organizational, social, economic or health care

  14. Postnatal irradiation-induced hippocampal neuropathology, cognitive impairment and aging.

    PubMed

    Tang, Feng Ru; Loke, Weng Keong; Khoo, Boo Cheong

    2017-04-01

    Irradiation of the brain in early human life may set abnormal developmental events into motion that last a lifetime, leading to a poor quality of life for affected individuals. While the effect of irradiation at different early developmental stages on the late human life has not been investigated systematically, animal experimental studies suggest that acute postnatal irradiation with ⩾0.1Gy may significantly reduce neurogenesis in the dentate gyrus and endotheliogenesis in cerebral vessels and induce cognitive impairment and aging. Fractionated irradiation also reduces neurogenesis. Furthermore, irradiation induces hippocampal neuronal loss in CA1 and CA3 areas, neuroinflammation and reduces gliogenesis. The hippocampal neurovascular niche and the total number of microvessels are also changed after radiation exposures. Each or combination of these pathological changes may cause cognitive impairment and aging. Interestingly, acute irradiation of aged brain with a certain amount of radiation has also been reported to induce brain hormesis or neurogenesis. At molecular levels, inflammatory cytokines, chemokines, neural growth factors, neurotransmitters, their receptors and signal transduction systems, reactive oxygen species are involved in radiation-induced adverse effect on brain development and functions. Further study at different omics levels after low dose/dose rate irradiation may not only unravel the mechanisms of radiation-induced adverse brain effect or hormesis, but also provide clues for detection or diagnosis of radiation exposure and for therapeutic approaches to effectively prevent radiation-induced cognitive impairment and aging. Investigation focusing on radiation-induced changes of critical brain development events may reveal many previously unknown adverse effects.

  15. 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.

  16. Postnatal neurogenesis in the cow pineal gland: an immunohistochemical study.

    PubMed

    Gómez Esteban, M B; Muñoz Mosqueira, M I; Arroyo, A A; Muñoz Barragán, L

    2013-03-01

    In the pineal gland of cows and rats structures designated rosettes have been described both during embryonic development and in adult animals. In order to investigate the possible nature of the cells comprising such structures, in the present work we studied the pineal glands from 10 cows of one- or four-years-old using conventional immunocytochemical and confocal microscopy techniques. As markers of glial cells, we used anti-vimentin (Vim) and glial fibrillary acidic protein (GFAP) and anti-S-100 sera, and the pinealocytes were labelled with β-III tubulin. As a marker of stem cells, we used an antinestin serum, while an anti-PCNA serum was employed to label proliferating cells. To explore the neuronal nature of some cells of the rosettes, we used an anti-SRIF serum. The rosettes were seen to be present throughout the glandular parenchyma and displayed a central cavity surrounded by cells, most of which expressed all or just some of the above glial labels and nestin, although there were also some rosettes with cells that expressed β-III tubulin and other cells that expressed SRIF. Likewise, in the cells of the rosettes the cell nucleus showed strong expression of PCNA. Confocal microscopy revealed that the walls of the rosettes contained cells that coexpressed Vim/S-100, Vim/GFAP and Vim/nestin. The number of rosettes was significantly greater in the animals of one year of age with respect to the four-year-old cows. The present findings allow us to suggest that rosettes are evolving structures and that most of the cells present in their walls should be considered stem cells, and hence responsible for the postnatal neurogenesis occurring in the pineal gland of cows.

  17. Postnatal arsenic exposure and attention impairment in school children.

    PubMed

    Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

    2016-01-01

    additional evidence that postnatal arsenic exposure impairs neurological function in children.

  18. Eating behavior, prenatal and postnatal growth in Angelman syndrome.

    PubMed

    Mertz, Line G B; Christensen, Rikke; Vogel, Ida; Hertz, Jens M; Østergaard, John R

    2014-11-01

    The objectives of the present study were to investigate eating behavior and growth parameters in Angelman syndrome. We included 39 patients with Angelman syndrome. Twelve cases had a larger Class I deletion, eighteen had a smaller Class II deletion, whereas paternal uniparental disomy (pUPD) or a verified UBE3A mutation were present in five and four cases, respectively. Eating behavior was assessed by a questionnaire. Anthropometric measures were obtained from medical records and compared to Danish reference data. Children with pUPD had significantly larger birth weight and birth length than children carrying a deletion or a UBE3A mutation. We found no difference in birth weight or length in children with Class I or Class II deletions. When maternal birth weight and/or birth weight of siblings were taken into consideration, children with Class I deletion had a lower weight at birth than expected, and the weight continued to be reduced during the investigated initial five years of life. In contrast, children with pUPD showed hyperphagic behavior and their weight increased significantly after the age of two years. Accordingly, their body mass index was significantly increased as compared to children with a deletion. At birth, one child showed microcephaly. At five years of age, microcephaly was observed in half of the deletion cases, but in none of the cases with a UBE3A mutation or pUPD. The apparently normal cranial growth in the UBE3A and pUPD patients should however be regarded as the result of a generally increased growth. Eating behavior, pre- and postnatal growth in children with Angelman syndrome depends on genotype.

  19. Impact of uteroplacental insufficiency on postnatal rat male gonad

    PubMed Central

    Germani, Daniela; Puglianiello, Antonella; Stukenborg, Jan-Bernd; Reda, Ahmed; Savchuk, Iuliia; Kjartansdóttir, Kristín Rós; Cianfarani, Stefano; Söder, Olle

    2016-01-01

    Prenatal events such as intrauterine growth restriction can affect gonadal development of the offspring and have an impact on reproductive health. To investigate the effects of intrauterine growth restriction induced by uterine artery ligation on the postnatal rat testis. Pregnant rats underwent uterine artery ligation at day 19 of gestation. Offspring were killed at 5, 20 and 40 days post-partum (dpp). At killing, one gonad was snap-frozen in liquid nitrogen and processed for RNA and steroid extraction. The other gonad was formalin-fixed for histology. Gene expression was analyzed by TaqMan Low-Density Array. Intratesticular testosterone, estradiol and serum gonadotrophins were measured. Thirty genes were dysregulated in intrauterine growth-restricted rats compared to controls, among which markers of Sertoli cell and Leydig cell function, cell metabolism and growth factors. Testis weights were significantly reduced at 5 and 20 dpp in intrauterine growth-restricted rats and caught-up by 40 dpp. Accordingly, Sertoli cell number was significantly lower in 5 dpp intrauterine growth-restricted rats. At 20 dpp, intratesticular testosterone was significantly increased in intrauterine growth-restricted rats, whereas serum gonadotrophins were unchanged. IUGR altered the gene expression in the rat testes up to peripubertal age and reduced testis size and Sertoli cell number in neonatal age. Multiple mechanisms encompassing genetic changes and steroid production by the testis may be involved in the catch-up growth phase that restored testis size by 40 dpp. Permanent consequences on organ function and gamete integrity cannot be excluded and deserve further investigations. PMID:27885054

  20. 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

  1. Postnatal mental distress in relation to the sociocultural practices of childbirth: An exploratory qualitative study from Ethiopia☆

    PubMed Central

    Hanlon, Charlotte; Whitley, Rob; Wondimagegn, Dawit; Alem, Atalay; Prince, Martin

    2009-01-01

    Sociocultural patterning of the postnatal period in non-Western settings has been hypothesised to protect against postnatal depression. In 2004, in a predominantly rural area of Ethiopia, we conducted 25 in-depth interviews and five focus group discussions with purposively selected participants including perinatal women, fathers, grandmothers, traditional and religious leaders, birth attendants and community leaders. Our main objectives were (1) to examine societal recognition of problematic distress states in the postnatal period and relate this to Western conceptualisations of postnatal depression and (2) to relate the occurrence of distress states to sociocultural patterning of the postnatal period. Inductive analysis was employed to identify salient themes. Participants spontaneously described culturally problematic distress states occurring in the postnatal period, although did not consider them to be illness. Vulnerability and danger of the postnatal period was emphasised, with risk of supernatural attack and physical harm leading to distress states. Participants also spoke of how gender disadvantage and economic strain intersect with cultural patterning of the postnatal period, threatening mental health due to the resulting disappointed expectations and exclusion, as well as exacerbation of pre-existing problems. Cultural dissonance, where a person's beliefs or actions are out of kilter with strong prevailing cultural norms, may be an important risk factor for postnatal distress in rural Ethiopia, where the postnatal period is extensively culturally elaborated. PMID:19709793

  2. Postnatal mental distress in relation to the sociocultural practices of childbirth: an exploratory qualitative study from Ethiopia.

    PubMed

    Hanlon, Charlotte; Whitley, Rob; Wondimagegn, Dawit; Alem, Atalay; Prince, Martin

    2009-10-01

    Sociocultural patterning of the postnatal period in non-Western settings has been hypothesised to protect against postnatal depression. In 2004, in a predominantly rural area of Ethiopia, we conducted 25 in-depth interviews and five focus group discussions with purposively selected participants including perinatal women, fathers, grandmothers, traditional and religious leaders, birth attendants and community leaders. Our main objectives were (1) to examine societal recognition of problematic distress states in the postnatal period and relate this to Western conceptualisations of postnatal depression and (2) to relate the occurrence of distress states to sociocultural patterning of the postnatal period. Inductive analysis was employed to identify salient themes. Participants spontaneously described culturally problematic distress states occurring in the postnatal period, although did not consider them to be illness. Vulnerability and danger of the postnatal period was emphasised, with risk of supernatural attack and physical harm leading to distress states. Participants also spoke of how gender disadvantage and economic strain intersect with cultural patterning of the postnatal period, threatening mental health due to the resulting disappointed expectations and exclusion, as well as exacerbation of pre-existing problems. Cultural dissonance, where a person's beliefs or actions are out of kilter with strong prevailing cultural norms, may be an important risk factor for postnatal distress in rural Ethiopia, where the postnatal period is extensively culturally elaborated.

  3. Postnatal Notch1 activation induces T‑cell malignancy in conditional and inducible mouse models.

    PubMed

    Liu, Ju; Dong, Fengyun; Fung, Iris; Chen, Edwin; Allen, Thaddeus D; Deutsch, Urban; Lobe, Corrinne G

    2014-11-01

    The Notch1 signaling pathway is essential for hematopoietic development. However, the effects of postnatal activation of Notch1 signaling on hematopoietic system is not yet fully understood. We previously generated ZEG‑IC‑Notch1 transgenic mice that have a floxed β‑geo/stop signal between a CMV promoter and intracellular domain of Notch1 (IC‑Notch1). Constitutively active IC‑Notch1 is silent until the introduction of Cre recombinase. In this study, endothelial/hematopoietic specific expression of IC‑Notch1 in double transgenic ZEG‑IC‑Notch1/Tie2‑Cre embryos induced embryonic lethality at E9.5 with defects in vascular system but not in hematopoietic system. Inducible IC‑Notch1 expression in adult mice was achieved by using tetracycline regulated Cre system. The ZEG‑IC‑Notch1/Tie2‑tTA/tet‑O‑Cre triple transgenic mice survived embryonic development when maintained on tetracycline. Post‑natal withdrawal of tetracycline induced expression of IC‑Notch1 transgene in hematopoietic cells of adult mice. The triple transgenic mice displayed extensive T‑cell infiltration in multiple organs and T‑cell malignancy of lymph nodes. In addition, the protein levels of p53 and alternative reading frame (ARF) were decreased in lymphoma‑like neoplasms from the triple transgenic mice while their mRNA expression remained unchanged, suggesting that IC‑Notch1 might repress ARF‑p53 pathway by a post‑transcriptional mechanism. This study demonstrated that activation of constitutive Notch1 signaling after embryonic development alters adult hematopoiesis and induces T‑cell malignancy.

  4. Prenatal ethanol increases sucrose reinforcement, an effect strengthened by postnatal association of ethanol and sucrose.

    PubMed

    Culleré, Marcela Elena; Spear, Norman E; Molina, Juan Carlos

    2014-02-01

    Late prenatal exposure to ethanol recruits sensory processing of the drug and of its motivational properties, an experience that leads to heightened ethanol affinity. Recent studies indicate common sensory and neurobiological substrates between this drug and sweet tastants. Using a recently developed operant conditioning technique for infant rats, we examined the effects of prenatal ethanol history upon sucrose self-administration (postnatal days, PDs 14-17). Prior to the last conditioning session, a low (0.5 g/kg) or a high (2.5 g/kg) ethanol dose were paired with sucrose. The intention was to determine if ethanol would inflate or devalue the reinforcing capability of the tastant and if these effects are dependent upon prenatal ethanol history. Male and female pups prenatally exposed to ethanol (2.0 g/kg) responded more when reinforced with sucrose than pups lacking this antenatal experience. Independently of prenatal status, a low ethanol dose (0.5 g/kg) enhanced the reinforcing capability of sucrose while the highest dose (2.5 g/kg) seemed to ameliorate the motivational properties of the tastant. During extinction (PD 18), two factors were critical in determining persistence of responding despite reinforcement omission. Pups prenatally exposed to ethanol that subsequently experienced the low ethanol dose paired with sucrose, showed higher resistance to extinction. The effects here reported were not associated with differential blood alcohol levels across prenatal treatments. These results indicate that fetal ethanol experience promotes affinity for a natural sweet reinforcer and that low doses of ethanol are also capable of enhancing the positive motivational consequences of sucrose when ethanol and sucrose are paired during infancy.

  5. Selective ablation of pillar and deiters' cells severely affects cochlear postnatal development and hearing in mice.

    PubMed

    Mellado Lagarde, Marcia M; Cox, Brandon C; Fang, Jie; Taylor, Ruth; Forge, Andrew; Zuo, Jian

    2013-01-23

    Mammalian auditory hair cells (HCs) are inserted into a well structured environment of supporting cells (SCs) and acellular matrices. It has been proposed that when HCs are irreversibly damaged by noise or ototoxic drugs, surrounding SCs seal the epithelial surface and likely extend the survival of auditory neurons. Because SCs are more resistant to damage than HCs, the effects of primary SC loss on HC survival and hearing have received little attention. We used the Cre/loxP system in mice to specifically ablate pillar cells (PCs) and Deiters' cells (DCs). In Prox1CreER(T2)+/-;Rosa26(DTA/+) (Prox1DTA) mice, Cre-estrogen receptor (CreER) expression is driven by the endogenous Prox1 promoter and, in presence of tamoxifen, removes a stop codon in the Rosa26(DTA/+) allele and induces diphtheria toxin fragment A (DTA) expression. DTA produces cell-autonomous apoptosis. Prox1DTA mice injected with tamoxifen at postnatal days 0 (P0) and P1 show significant DC and outer PC loss at P2-P4, that reaches ∼70% by 1 month. Outer HC loss follows at P14 and is almost complete at 1 month, while inner HCs remain intact. Neural innervation to the outer HCs is disrupted in Prox1DTA mice and auditory brainstem response thresholds in adults are 40-50 dB higher than in controls. The hearing deficit correlates with loss of cochlear amplification. Remarkably, in Prox1DTA mice, the auditory epithelium preserves the ability to seal the reticular lamina and spiral ganglion neuron counts are normal, a key requirement for cochlear implant success. In addition, our results show that cochlear SC pools should be appropriately replenished during HC regeneration strategies.

  6. Prenatal Ethanol Increases Sucrose Reinforcement, an Effect Strengthened by Postnatal Association of Ethanol and Sucrose

    PubMed Central

    Culleré, Marcela Elena; Spear, Norman E.; Molina, Juan Carlos

    2014-01-01

    Late prenatal exposure to ethanol recruits sensory processing of the drug and of its motivational properties, an experience that leads to heightened ethanol affinity. Recent studies indicate common sensory and neurobiological substrates between this drug and sweet tastants. Using a recently developed operant conditioning technique for infant rats, we examined the effects of prenatal ethanol history upon sucrose self-administration (postnatal days, PDs 14–17). Prior to the last conditioning session, a low (0.5 g/kg) or a high (2.5 g/kg) ethanol dose were paired with sucrose. The intention was to determine if ethanol would inflate or devalue the reinforcing capability of the tastant and if these effects are dependent upon prenatal ethanol history. Male and female pups prenatally exposed to ethanol (2.0 g/kg) responded more when reinforced with sucrose than pups lacking this antenatal experience. Independently of prenatal status, a low ethanol dose (0.5 g/kg) enhanced the reinforcing capability of sucrose while the highest dose (2.5 g/kg) seemed to ameliorate the motivational properties of the tastant. During extinction (PD 18), two factors were critical in determining persistence of responding despite reinforcement omission. Pups prenatally exposed to ethanol that subsequently experienced the low ethanol dose paired with sucrose, showed higher resistance to extinction. The effects here reported were not associated with differential blood alcohol levels across prenatal treatments. These results indicate that fetal ethanol experience promotes affinity for a natural sweet reinforcer and that low doses of ethanol are also capable of enhancing the positive motivational consequences of sucrose when ethanol and sucrose are paired during infancy. PMID:24398347

  7. Postnatal Pancreas of Mice Contains Tripotent Progenitors Capable of Giving Rise to Duct, Acinar, and Endocrine Cells In Vitro.

    PubMed

    Ghazalli, Nadiah; Mahdavi, Alborz; Feng, Tao; Jin, Liang; Kozlowski, Mark T; Hsu, Jasper; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2015-09-01

    Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells for treating type 1 diabetes. However, it remains unclear whether young (1-week-old) pancreas harbors multipotent progenitors capable of differentiating into duct, acinar, and endocrine cells. Laminin is an extracellular matrix (ECM) protein important for β-cells' survival and function. We established an artificial extracellular matrix (aECM) protein that contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin (designated aECM-lam). Whether IKVAV is necessary for endocrine differentiation in vitro is unknown. To answer these questions, we cultured single cells from 1-week-old pancreas in semi-solid media supplemented with aECM-lam, aECM-scr (which contains a scrambled sequence instead of IKVAV), or Matrigel. We found that colonies were generated in all materials. Individual colonies were examined by microfluidic reverse transcription-polymerase chain reaction, immunostaining, and electron microscopy analyses. The majority of the colonies expressed markers for endocrine, acinar, and ductal lineages, demonstrating tri-lineage potential of individual colony-forming progenitors. Colonies grown in aECM-lam expressed higher levels of endocrine markers Insulin1, Insulin2, and Glucagon compared with those grown in aECM-scr and Matrigel, indicating that the IKVAV sequence enhances endocrine differentiation. In contrast, Matrigel was inhibitory for endocrine gene expression. Colonies grown in aECM-lam displayed the hallmarks of functional β-cells: mature insulin granules and glucose-stimulated insulin secretion. Colony-forming progenitors were enriched in the CD133(high) fraction and among 230 micro-manipulated single CD133(high) cells, four gave rise to colonies that expressed tri-lineage markers. We conclude that young postnatal pancreas contains multipotent progenitor cells and that aECM-lam promotes differentiation of β-like cells in vitro.

  8. Maternal Omega-3 Supplement Improves Dopaminergic System in Pre- and Postnatal Inflammation-Induced Neurotoxicity in Parkinson's Disease Model.

    PubMed

    Delattre, Ana Marcia; Carabelli, Bruno; Mori, Marco Aurélio; Kempe, Paula G; Rizzo de Souza, Luiz E; Zanata, Silvio M; Machado, Ricardo B; Suchecki, Deborah; Andrade da Costa, Belmira L S; Lima, Marcelo M S; Ferraz, Anete C

    2017-04-01

    Evidence suggests that idiopathic Parkinson's disease (PD) is the consequence of a neurodevelopmental disruption, rather than strictly a consequence of aging. Thus, we hypothesized that maternal supplement of omega-3 polyunsaturated fatty acids (ω-3 PUFA) may be associated with neuroprotection mechanisms in a self-sustaining cycle of neuroinflammation and neurodegeneration in lipopolysaccharide (LPS)-model of PD. To test this hypothesis, behavioral and neurochemical assay were performed in prenatally LPS-exposed offspring at postnatal day 21. To further determine whether prenatal LPS exposure and maternal ω-3 PUFAs supplementation had persisting effects, brain injury was induced on PN 90 rats, following bilateral intranigral LPS injection. Pre- and postnatal inflammation damage not only affected dopaminergic neurons directly, but it also modified critical features, such as activated microglia and astrocyte cells, disrupting the support provided by the microenvironment. Unexpectedly, our results failed to show any involvement of caspase-dependent and independent apoptosis pathway in neuronal death mechanisms. On the other hand, learning and memory deficits detected with a second toxic exposure were significantly attenuated in maternal ω-3 PUFAs supplementation group. In addition, ω-3 PUFAs promote beneficial effect on synaptic function, maintaining the neurochemical integrity in remaining neurons, without necessarily protect them from neuronal death. Thus, our results suggest that ω-3 PUFAs affect the functional ability of the central nervous system in a complex way in a multiple inflammation-induced neurotoxicity animal model of PD and they disclose new ways of understanding how these fatty acids control responses of the brain to different challenges.

  9. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    PubMed Central

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

  10. 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

  11. Influence of prenatal and postnatal fraternity size on reproduction in swine.

    PubMed

    Kirkpatrick, B W; Rutledge, J J

    1988-10-01

    Hypotheses of a negative association between fraternity size (size of litter in which an individual develops prior to birth or is reared following birth) and ovulation rate or litter size were tested by examining reproduction of females born or reared in varying prenatal and postnatal fraternities. Gifts were randomly assigned to develop prenatally and be reared postnatal in small or large fraternities. Dams of experimental animals were randomly assigned to one of two prenatal fraternity size treatments, either unilateral oviductal ligation (to bear a small prenatal litter) or no ligation (to bear a normal prenatal litter). Whereas this did result in differences (P less than .01) in litter size at birth (small = 6.2 +/- .4 vs large = 9.6 +/- .9), there was considerable overlap in observed litter sizes between ligated and nonligated dams. Consequently, effects of prenatal fraternity size were examined by regression. Distinct differences in postnatal fraternity size were created by randomly assigning piglets to small (5 piglets) or large (10 piglets) postnatal fraternities within 24 h of birth. Differences in postnatal fraternity size were maintained through weaning at 3 wk (small = 4.9 +/- .1 vs large = 9.4 +/- .2). Weights at birth (regression of birth weight on prenatal fraternity size = -.07 +/- .02, P less than .01) and weaning (small = 6.09 +/- .15 vs large = 5.46 +/- .17 kg, P less than .01) were heavier for gilts from small prenatal and postnatal fraternities, respectively, compared with gilts from large fraternities. Effects of prenatal and postnatal size on BW did not persist following weaning (P greater than .20).

  12. 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.

  13. 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

  14. The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats

    PubMed Central

    Özgür, Erdoğan; Gürbüz Özgür, Börte; Aksu, Hatice; Cesur, Gökhan

    2016-01-01

    Objective: The aim of this study was to investigate depression-like behaviors of juvenile rats with congenital and postnatal hypothyroidism. Methods: Twenty-seven newborn rat pups were used. First, 6-month-old Wistar Albino female rats were impregnated. Methimazole (0.025% wt/vol) was given to dam rats from the first day of pregnancy until postnatal 21 days (P21) to generate pups with congenital hypothyroidism (n=8), whereas in the postnatal hypothyroidism group (n=10), methimazole was given from P0 to P21. In the control group (n=9), dam rats were fed ad libitum and normal tap water. Offspring were fed with breast milk from their mothers. The behavioral parameters were measured with the juvenile forced swimming test (JFST). The procedure of JFST consisted of two sessions in two consecutive days: the 15-minute pre-test on day 1 and the 5-minute test on day 2. Results: Increased immobility and decreased climbing duration were observed in both congenital and postnatal hypothyroidism groups. Decreased swimming duration was detected in the postnatal hypothyroidism group. Both hypothyroidism groups had a lower body weight gain compared with the control group, while the congenital hypothyroidism group had the lowest body weight. Conclusion: Our results showed that hypothyroidism had negative effects on depression-like behavior as well as on growth and development. Both congenital and postnatal hypothyroidism caused an increase in immobility time in JFST. New studies are required to understand the differing results on depression-like behavior between congenital and postnatal hypothyroidism. PMID:27611926

  15. 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

  16. 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.

  17. Critical appraisal of different anthropometric charts to evaluate postnatal growth of preterm infants.

    PubMed

    Bertino, E; Coscia, A; Arslanoglu, S; Cresi, F; Sabatino, G; Giuliani, F; Chiale, F; Occhi, L; Martano, C; Gilli, G

    2012-01-01

    Preterm infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth, specifically in relation to the charts used. At present, the charts available in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. Recently, an international project has recently started aiming to create prescriptive standard for the evaluation of postnatal growth of preterm infants (INTERGROWTH-21st). Alternatively, at present, while specific charts for evaluating preterm infant postnatal growth are lacking, the best compromise is likely to be as follows: from birth to term neonatal anthropometric charts; International longitudinal charts WHO 2006 or CDC 2002 from term to childhood.

  18. Post-natal effect of overexpressed DKK1 on mandibular molar formation.

    PubMed

    Han, X L; Liu, M; Voisey, A; Ren, Y S; Kurimoto, P; Gao, T; Tefera, L; Dechow, P; Ke, H Z; Feng, J Q

    2011-11-01

    Dickkopf-related protein 1 (DKK1) is a potent inhibitor of Wnt/β-catenin signaling. Dkk1-null mutant embryos display severe defects in head induction. Conversely, targeted expression of Dkk1 in dental epithelial cells leads to the formation of dysfunctional enamel knots and subsequent tooth defects during embryonic development. However, its role in post-natal dentinogenesis is largely unknown. To address this issue, we studied the role of DKK1 in post-natal dentin development using 2.3-kb Col1a1-Dkk1 transgenic mice, with the following key findings: (1) The Dkk1 transgene was highly expressed in pulp and odontoblast cells during post-natal developmental stages; (2) the 1(st) molar displayed short roots, an enlarged pulp/root canal region, and a decrease in the dentin formation rate; (3) a small malformed second molar and an absent third molar; (4) an increase of immature odontoblasts, few mature odontoblasts, and sharply reduced dentinal tubules; and (5) a dramatic change in Osx and nestin expression. We propose that DKK1 controls post-natal mandibular molar dentin formation either directly or indirectly via the inhibition of Wnt signaling at the following aspects: (i) post-natal dentin formation, (ii) formation and/or maintenance of the dentin tubular system, (iii) mineralization of the dentin, and (iv) regulation of molecules such as Osx and nestin.

  19. In utero Transplanted Human Hepatocytes Allows for Postnatal Engraftment of Human Hepatocytes in Pigs

    PubMed Central

    Fisher, James E; Lillegard, Joseph B; Mckenzie, Travis J; Rodysill, Brian R; Wettstein, Peter J; Nyberg, Scott L

    2012-01-01

    In utero cell transplantation (IUCT) can lead to postnatal engraftment of human cells in the xenogeneic recipient. Most reports of IUCTs have involved hematopoietic stem cells. It is unknown if human hepatocytes used for IUCT in fetal pigs will lead to engraftment of these same cells in the postnatal environment. In this study, fetal pigs received direct liver injections of 1×107 human hepatocytes in utero and were delivered by cesarean-section at term. Piglets received a second direct liver injection of 5×107 human hepatocytes 1 week postnatally. Serum was analyzed for human albumin at 2, 4, and 6 weeks post-engraftment. Piglet livers were harvested 6 weeks after transplantation and examined by immunohistochemistry, PCR and fluorescence in situ hybridization for human specific sequences. Piglets receiving IUCT with human hepatocytes that were postnatally engrafted with human hepatocytes showed significant levels of human albumin production in their serum at all post-engraftment time points. Human albumin gene expression, the presence of human hepatocytes and the presence of human beta-2 microglobulin were all confirmed 6 weeks post-engraftment. IUCT in fetal pigs using human hepatocytes early in gestation allowed for engraftment of human hepatocytes, which remained viable and functional for weeks after transplantation. IUCT followed by postnatal engraftment may provide a future means for large scale expansion of human hepatocytes in genetically-engineered pigs. PMID:23280879

  20. Intrauterine growth correlation to postnatal growth--influence of risk factors and complications in pregnancy.

    PubMed

    Larsen, T; Greisen, G; Petersen, S

    1997-01-20

    In a population of 616 pregnant women with increased risk of intrauterine growth retardation, we examined the relationship of third trimester fetal growth to maternal and pregnancy risk factors, the infants condition at birth, and postnatal growth. Intrauterine growth velocity was calculated from repeated estimations of fetal weight using ultrasound. Postnatal growth up to 3 months was measured in 313 of the infants. Intrauterine growth velocity was directly correlated to birth weight deviation (R = 0.35, P < 0.0001) and inversely correlated to postnatal growth (R = 0.21, P = 0.0001). Heavy smoking throughout pregnancy was the most pronounced factor associated with loss of fetal growth percentiles (P = 0.006), and it was also associated with postnatal catchup (P = 0.01). Infants who needed neonatal care had significantly lower intrauterine growth velocities compared to the rest of the study group; no correlation was found between intrauterine growth velocity and Apgar scores or umbilical pH. It is concluded that growth retardation in the third trimester can be identified by ultrasound fetometry, and is associated with maladaptation at birth and postnatal catchup. However, the correlations were weak suggesting that deviation at birth reflects, only to a limited degree, acceleration or deceleration of growth in the third trimester.

  1. Maternal Bonding through Pregnancy and Postnatal: Findings from an Australian Longitudinal Study.

    PubMed

    Rossen, Larissa; Hutchinson, Delyse; Wilson, Judy; Burns, Lucinda; Allsop, Steve; Elliott, Elizabeth J; Jacobs, Sue; Macdonald, Jacqui A; Olsson, Craig; Mattick, Richard P

    2017-02-17

    Background Mother-infant bonding provides the foundation for secure attachment through the lifespan and organizes many facets of infant social-emotional development, including later parenting. Aims To describe maternal bonding to offspring across the pregnancy and postnatal periods, and to examine a broad range of sociodemographic and psychosocial predictors of the maternal-offspring bond. Methods Data were drawn from a sample of 372 pregnant women participating in an Australian population-based longitudinal study of postnatal health and development. Participants completed maternal bonding questionnaires at each trimester and 8 weeks postnatal. Data were collected on a range of sociodemographic and psychosocial factors. Results Bonding increased significantly through pregnancy, in quality and intensity. Regression analyses indicated that stronger antenatal bonding at all time points (trimesters 1 through 3) predicted stronger postnatal bonding. Older maternal age, birth mother being born in a non-English speaking country, mother not working full time, being a first-time mother, breast-feeding problems, and baby's crying behavior all predicted poorer bonding at 8 weeks postpartum. Conclusion These novel findings have important implications for pregnant women and their infant offspring, and for health care professionals working in perinatal services. Importantly, interventions to strengthen maternal-fetal bonding would be beneficial during pregnancy to enhance postnatal bonding and infant health outcomes.

  2. 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.

  3. Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Rats

    PubMed Central

    Smith, Catherine A.; Farmer, Kyle; Lee, Hyunmin; Holahan, Matthew R.; Smith, Jeffrey C.

    2015-01-01

    Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl) phthalate (DEHP) disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females. PMID:26516880

  4. Critical role of androgen receptor in the postnatal period in male sexual behavior in rats.

    PubMed

    Yamada, Shunji; Ohoya, Miku; Takanami, Keiko; Matsuda, Ken Ichi; Kawata, Mitsuhiro

    2015-11-16

    Gonadal hormones have a developmental role in organization of the nervous system that regulates sexually dimorphic behavior. It is well known that androgen secreted from testes in the perinatal period is converted to estrogen by aromatase in rodent brain, and that estrogen and its receptor play a pivotal role in masculinization of brain structure and function. Treatment with flutamide, an androgen receptor (AR) antagonist, during the perinatal period inhibits development of malespecific brain structure and function, suggesting that androgen signaling via AR also influences brain masculinization. In this study, we investigated which stage during the postnatal period is critical for androgen signaling in brain masculinization. The postnatal period was designated as postnatal days (PD) 0-22, and divided into stages I (PD 0-7), II (PD 8-14), and III (PD 15-22). Newborn male rats were given flutamide subcutaneously in each stage. After adulthood, the effects of postnatal flutamide treatment on brain masculinization were evaluated byanalysis of male sexual behavior. Continuous inhibition of AR throughout stages I and II caused a robust reduction of the intromission ratio and ejaculation frequency compared with other groups. AR inhibition in stage I, II, or III did not cause any change. AR inhibition had no effect onmount behavior. These results show that stage-specific AR activation in the first two postnatal weeks may contribute to brain masculinization mediating male sexual behavior in adulthood.

  5. [Review and guidelines on the prevention, diagnosis and treatment of post-natal cytomegalovirus infection].

    PubMed

    Alarcón Allen, A; Baquero-Artigao, F

    2011-01-01

    Postnatal cytomegalovirus (CMV) infection in the newborn can occur from exposure to maternal cervical secretions during birth, ingestion of breast milk, transfusion of blood products or transmission by body fluids of infected people. Breast milk is the main source of infection, given the high rate of CMV-positive mothers excreting CMV in milk. Freezing reduces the risk of CMV transmission by breastfeeding, although it does not eliminate it completely. Pasteurisation prevents such transmission, but it can alter the immunological properties of breast milk. Postnatal CMV infection is usually asymptomatic, as it normally results from viral reactivation in the mother, and the neonate is born with protective antibodies. However, in the very low birth weight premature infant the amount of transferred antibodies is smaller and a symptomatic infection can occur. Symptomatic post-natal CMV infection in the newborn typically causes hepatitis, neutropenia, thrombocytopenia or sepsis-like syndrome. Pneumonitis and enteritis are less common, but very characteristic. Diagnosis is based on urine virus detection at the time of onset of symptoms. Postnatal CMV infection in the newborn generally resolves spontaneously without antiviral treatment. Ganciclovir should be reserved for severe cases. Unlike congenital CMV disease, post-natal CMV infection in the preterm infant does not seem to be associated with hearing loss or abnormal neuro-development in long term follow-up.

  6. Dynamic expression of neurotrophic factor receptors in postnatal spinal motoneurons and in mouse model of ALS.

    PubMed

    Zhang, Jiasheng; Huang, Eric J

    2006-07-01

    Neurotrophic factors support the survival of spinal motoneurons (MNs) and have been considered as strong candidates for treating motoneuron diseases. However, it is unclear if the right combination of neurotrophic factor receptors is present in postnatal spinal MNs. In this study, we show that the level of c-ret expression remains relatively stable in embryonic and postnatal spinal MNs. In contrast, the mRNA and protein of GFRalpha1 and -2 are progressively down-regulated in postnatal life. By 3 and 6 months of age, both receptors are barely detectable in spinal MNs. The down-regulation of GFRalpha1 appears accelerated in transgenic mice expressing mutant SOD1(G93A). Despite the progressive loss of GFRalpha1 and -2, phosphorylation of c-ret shows no detectable reduction on tyrosine residues or on serine 696. In addition to the GFRalpha subunits, expression of TrkB also shows a dynamic change. During embryogenesis, there is twice as much full-length TrkB as the truncated TrkB isoform. However, this ratio is reversed in postnatal spinal cord. Expression of the mutant SOD1(G93A) appears to have no effect on the TrkB receptor ratio. Taken together, our data indicate that the expression of neurotrophic factor receptors, GFRalpha1, -2, and TrkB, is not static, but undergoes dynamic changes in postnatal spinal MNs. These results provide insights into the use of neurotrophic factors as therapeutic agents for ALS.

  7. 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

  8. Health Promotion

    PubMed Central

    Wilson, Ron

    1992-01-01

    How physicians address issues of disease prevention and health promotion is discussed and current standards of screening for disease and counseling practices are reviewed. Collaboration among all health professionals is necessary if preventive medicine is to be effective. PMID:21221259

  9. Transcriptional Profiling of Intrinsic PNS Factors in the Postnatal Mouse

    PubMed Central

    Smith, Robin P.; Lerch-Haner, Jessica K.; Pardinas, Jose R.; Buchser, William J.; Bixby, John L.; Lemmon, Vance P.

    2010-01-01

    Neurons in the peripheral nervous system (PNS) display a higher capacity to regenerate after injury than those in the central nervous system, suggesting cell specific transcriptional modules underlying axon growth and inhibition. We report a systems biology based search for PNS specific transcription factors (TFs). Messenger RNAs enriched in dorsal root ganglion (DRG) neurons compared to cerebellar granule neurons (CGNs) were identified using subtractive hybridization and DNA microarray approaches. Network and transcription factor binding site enrichment analyses were used to further identify TFs that may be differentially active. Combining these techniques, we identified 32 TFs likely to be enriched and/or active in the PNS. Twenty-five of these TFs were then tested for an ability to promote CNS neurite outgrowth in an overexpression screen. Real-time PCR and immunohistochemical studies confirmed that one representative TF, STAT3, is intrinsic to PNS neurons, and that constitutively active STAT3 is sufficient to promote CGN neurite outgrowth. PMID:20696251

  10. Transcriptional profiling of intrinsic PNS factors in the postnatal mouse.

    PubMed

    Smith, Robin P; Lerch-Haner, Jessica K; Pardinas, Jose R; Buchser, William J; Bixby, John L; Lemmon, Vance P

    2011-01-01

    Neurons in the peripheral nervous system (PNS) display a higher capacity to regenerate after injury than those in the central nervous system, suggesting cell specific transcriptional modules underlying axon growth and inhibition. We report a systems biology based search for PNS specific transcription factors (TFs). Messenger RNAs enriched in dorsal root ganglion (DRG) neurons compared to cerebellar granule neurons (CGNs) were identified using subtractive hybridization and DNA microarray approaches. Network and transcription factor binding site enrichment analyses were used to further identify TFs that may be differentially active. Combining these techniques, we identified 32 TFs likely to be enriched and/or active in the PNS. Twenty-five of these TFs were then tested for an ability to promote CNS neurite outgrowth in an overexpression screen. Real-time PCR and immunohistochemical studies confirmed that one representative TF, STAT3, is intrinsic to PNS neurons, and that constitutively active STAT3 is sufficient to promote CGN neurite outgrowth.

  11. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1

    PubMed Central

    Yan, Naihong; Cheng, Lin; Cho, Kinsang; Malik, Muhammad Taimur A.; Xiao, Lirong; Guo, Chenying; Yu, Honghua; Zhu, Ruilin; Rao, Rajesh C.; Chen, Dong Feng

    2016-01-01

    Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy. PMID:27677711

  12. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring

    PubMed Central

    Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C.

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

  13. Child maltreatment and foster care: unpacking the effects of prenatal and postnatal parental substance use.

    PubMed

    Smith, Dana K; Johnson, Amber B; Pears, Katherine C; Fisher, Philip A; DeGarmo, David S

    2007-05-01

    Parental substance use is a well-documented risk for children. However, little is known about specific effects of prenatal and postnatal substance use on child maltreatment and foster care placement transitions. In this study, the authors unpacked unique effects of (a) prenatal and postnatal parental alcohol and drug use and (b) maternal and paternal substance use as predictors of child maltreatment and foster care placement transitions in a sample of 117 maltreated foster care children. Models were tested with structural equation path modeling. Results indicated that prenatal maternal alcohol use predicted child maltreatment and that combined prenatal maternal alcohol and drug use predicted foster care placement transitions. Prenatal maternal alcohol and drug use also predicted postnatal paternal alcohol and drug use, which in turn predicted foster care placement transitions. Findings highlight the potential integrative role that maternal and paternal substance use has on the risk for child maltreatment and foster care placement transitions.

  14. 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.

  15. The postnatal origin of adult neural stem cells and the effects of glucocorticoids on their genesis.

    PubMed

    Ortega-Martínez, Sylvia; Trejo, José L

    2015-02-15

    The relevance of adult neurogenesis in hippocampal function is well documented, as is the potential impact stress has on the adult neurogenic niche. Adult born neurons are generated from neural precursors in the dentate gyrus (DG), although the point in postnatal development that these cell precursors originate is not known. This is particularly relevant if we consider the effects stress may have on the development of neural precursors, and whether such effects on adult neurogenesis and behavior may persist in the long-term. We have analyzed the proportion of neural precursors in the adult murine hippocampus born on specific days during postnatal development using a dual birth-dating analysis, and we assessed their sensitivity to dexamethasone (DEX) on the peak day of cell generation. We also studied the consequences of postnatal DEX administration on adult hippocampal-dependent behavior. Postnatal day 6 (P6) is a preferred period for proliferating neural stem cells (NSCs) to become the precursors that remain in a proliferative state throughout adulthood. This window is independent of gender, the cell's location in the DG granule cell layer or their rostro-caudal position. DEX administration at P6 reduces the size of the adult NSC pool in the DG, which is correlated with poor learning/memory capacity and increased anxiety-like behavior. These results indicate that aNSCs are generated non-uniformly during postnatal development, with peak generation on day P6, and that stress receptor activation during the key period of postnatal NSC generation has a profound impact on both adult hippocampal neurogenesis and behavior.

  16. 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.

  17. The influence of prenatal and postnatal fraternity size on reproduction in mice.

    PubMed

    Kirkpatrick, B W; Rutledge, J J

    1987-05-01

    Effects of prenatal and postnatal fraternity size (size of litter in which an individual is reared) on age at vaginal opening, growth, and subsequent litter production were examined by rearing mice in standardized prenatal and postnatal fraternities in a 3 X 3 factorial design. Prenatal fraternity size was standardized by reducing litters of 14 or more to either 14, 10, or 6 fetuses on Day 9 of gestation. Postnatal fraternity size was standardized by assigning pups randomly to nurse in litters of 5, 10, or 15 pups within 24 h of birth. Both prenatal and postnatal fraternity size affected growth of the mice (p = 0.02 and p less than 0.01, respectively) with mice reared in small fraternities attaining greater weights throughout the study. Prenatal fraternity size had a negative linear effect on litter size at second parity and tended to have a positive linear effect on age at vaginal opening. Postnatal fraternity size affected age at vaginal opening (p less than 0.01), litter size at first parity (p less than 0.01), and litter size at second parity (p = 0.03). These effects were positive and linear for age at vaginal opening (p less than 0.01; small fraternity size associated with younger age at vaginal opening) and negative and linear for litter size at first and second parity (p less than 0.01 and p = 0.10, respectively; smaller fraternity size associated with larger litter size). There was no interaction between prenatal and postnatal fraternity size effects on age at vaginal opening or litter size (p greater than 0.20).

  18. Developmental Expression of Inositol 1, 4, 5-trisphosphate Receptor in the Post-Natal Rat Cochlea

    PubMed Central

    Liu, W. J.; Yang, J.

    2015-01-01

    Inositol 1, 4, 5-trisphosphate receptor (IP3R) has been established to be essential for hearing. However, the expression of IP3R in the cochlea in the period of auditory development remains unknown. We investigated the expression of IP3R in the developing rat cochlea using immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). We observed its presence in the developing rat cochlea, and changes in IP3R protein expressions from the early post-natal period to adult. At birth (postnatal day 0, P0), IP3R expression was only found in Hensen’s cell. IP3R immunoreactivity first appeared in the sensory hair cells in the organ of Corti at P2. This localization was confirmed by means of double-labeling experiments with Myosin VIIA, a marker for cochlear hair cells. Colocalization of IP3R and Myosin VIIA from P2 to the second post-natal week suggested early expression of IP3R in developing inner and outer hair cells. Claudius’ cells near the spiral ligament were labelled for IP3R from P8 onwards. Transient IP3R expression was observed in the stria vascularis in early post-natal rat from P4 to P8. Spiral ganglion neurons also exhibited weaker IP3R fluorescence signals during post-natal development. The results of RT-PCR demonstrated that all three IP3R isoforms (IP3R1, IP3R2, and IP3R3) were present in rat cochlea during four different developmental stages of cochlea, from P0 to P28. Present immunohistochemical evidence for both change and maintenance of expression of IP3R during post-natal development of the rat cochlea indicated the possible involvement of IP3R-mediated calcium signaling in cochlear development. PMID:26150157

  19. 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

  20. 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.

  1. 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.

  2. Health Promotion

    PubMed Central

    Karmali-Rawji, Shameela; Kassim-Lakha, Shaheen; Taylor, Karmel

    1992-01-01

    Perceived lack or loss of control, stress, a rapidly again population and rising costs of health care necessitate effective health promotion and disease prevention in the elderly. In a collaborative health promotion effort, the private sector, public sector, and community partners have joined to increase the South Asian elders' sense of control over the decisions and circumstances that affect their everyday lives. The project was designed to help elders come to terms with the fragmentation of their extended families, cultural alienation, decreased autonomy, need for information, and greater risk of cardiovascular disease. Imagesp622-a

  3. 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.

  4. [The postnatal development of the progeny of males whose germ cells were irradiated at different stages of spermatogenesis].

    PubMed

    Lepekhin, N P; Palyga, G F

    1995-01-01

    Distinct genetic radiosensitivity of germinal cells of males irradiated during different stages of spermatogenesis with doses of 0.25-5.0 Gy leads to reduction in vital newborn rats number in the first generation progeny and to elevated postnatal mortality rate. These postnatal ontogeny disorders depend on the irradiation dose and spermatogenesis stage for a moment irradiation.

  5. The Effects of Maternal Postnatal Depression and Child Sex on Academic Performance at Age 16 Years: A Developmental Approach

    ERIC Educational Resources Information Center

    Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Croudace, Tim; Cooper, Peter

    2010-01-01

    Background: Postnatal depression (PND) is associated with poor cognitive functioning in infancy and the early school years; long-term effects on academic outcome are not known. Method: Children of postnatally depressed (N = 50) and non-depressed mothers (N = 39), studied from infancy, were followed up at 16 years. We examined the effects on…

  6. Effects of Prenatal and Postnatal Parent Depressive Symptoms on Adopted Child HPA Regulation: Independent and Moderated Influences

    ERIC Educational Resources Information Center

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Harold, Gordon T.; Reiss, David

    2013-01-01

    This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck…

  7. Postnatal exposure to a high-carbohydrate diet interferes epigenetically with thyroid hormone receptor induction of the adult male rat skeletal muscle glucose transporter isoform 4 expression.

    PubMed

    Raychaudhuri, Nupur; Thamotharan, Shanthie; Srinivasan, Malathi; Mahmood, Saleh; Patel, Mulchand S; Devaskar, Sherin U

    2014-10-01

    Early life nutritional intervention causes adult-onset insulin resistance and obesity in rats. Thyroid hormone receptor (TR), in turn, transcriptionally enhances skeletal muscle Glut4 expression. We tested the hypothesis that reduced circulating thyroid-stimulating hormone and T4 concentrations encountered in postnatal (PN4-PN24) high-carbohydrate (HC) milk formula-fed versus the mother-fed controls (MF) would epigenetically interfere with TR induction of adult (100 days) male rat skeletal muscle Glut4 expression, thereby providing a molecular mechanism mediating insulin resistance. We observed increased DNA methylation of the CpG island with enhanced recruitment of Dnmt3a, Dnmt3b and MeCP2 in the glut4 promoter region along with reduced acetylation of histone (H)2A.Z and H4 particularly at the H4.lysine (K)16 residue, which was predominantly mediated by histone deacetylase 4 (HDAC4). This was followed by enhanced recruitment of heterochromatin protein 1β to the glut4 promoter with increased Suv39H1 methylase concentrations. These changes reduced TR binding of the T3 response element of the glut4 gene (TREs; -473 to -450 bp) detected qualitatively in vivo (electromobility shift assay) and quantified ex vivo (chromatin immunoprecipitation). In addition, the recruitment of steroid receptor coactivator and CREB-binding protein to the glut4 promoter-protein complex was reduced. Co-immunoprecipitation experiments confirmed the interaction between TR and CBP to be reduced and HDAC4 to be enhanced in HC versus MF groups. These molecular changes were associated with diminished skeletal muscle Glut4 mRNA and protein concentrations. We conclude that early postnatal exposure to HC diet epigenetically reduced TR induction of adult male skeletal muscle Glut4 expression, uncovering novel molecular mechanisms contributing to adult insulin resistance and obesity.

  8. Evaluation of changes in postnatal care using the "Parents' Postnatal Sense of Security" instrument and an assessment of the instrument's reliability and validity

    PubMed Central

    Kvist, Linda J; Persson, Eva K

    2009-01-01

    Background A sense of security is important for experiences of parenthood in the early postpartum period. The objectives of this study were to evaluate two models of postnatal care using a questionnaire incorporating the Parents' Postpartum Sense of Security (PPSS) instrument and to test the validity of the PPSS instrument. Methods Postal surveys were sent to 234 mothers who had experienced two different forms of postnatal care (study group and control group) and returned by 86.8%. These two groups of mothers were compared for total scores on the PPSS instrument. Demographic variables and mothers' opinions about care interventions were also compared and these variables were tested for correlations with the total PPSS score. A regression analysis was carried out to assess areas of midwifery care which might affect a sense of security. The internal consistency and concurrent validity of the instrument were tested for the total population. Results there were no significant differences between the groups for scores on the PPSS instrument. A total of three variables predicted 26% of the variability on the PPSS scores for the study group and five variables predicted 37% of the variability in the control group. One variable was common to both: "The midwives on the postnatal ward paid attention to the mother as an individual". There were significant correlations between the total PPSS scores and scores for postpartum talks and visits to the breastfeeding clinic. There was also a significant correlation between the single question: "I felt secure during the first postpartum week" and the total PPSS score. Tests for internal consistency and concurrent validity were satisfactory. Conclusion The proposed new model of care neither improved nor impaired mothers' feelings of security the week following birth. Being seen as an individual by the midwife who provides postnatal care may be an important variable for mothers' sense of postnatal security. It is possible that postpartum

  9. 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

  10. Profound morphological and functional changes of rodent Purkinje cells between the first and the second postnatal weeks: a metamorphosis?

    PubMed Central

    Dusart, Isabelle; Flamant, Frederic

    2012-01-01

    Between the first and the second postnatal week, the development of rodent Purkinje cells is characterized by several profound transitions. Purkinje cells acquire their typical dendritic “espalier” tree morphology and form distal spines. During the first postnatal week, they are multi-innervated by climbing fibers and numerous collateral branches sprout from their axons, whereas from the second postnatal week, the regression of climbing fiber multi-innervation begins, and Purkinje cells become innervated by parallel fibers and inhibitory molecular layer interneurons. Furthermore, their periods of developmental cell death and ability to regenerate their axon stop and their axons become myelinated. Thus a Purkinje cell during the first postnatal week looks and functions differently from a Purkinje cell during the second postnatal week. These fundamental changes occur in parallel with a peak of circulating thyroid hormone in the mouse. All these features suggest to some extent an interesting analogy with amphibian metamorphosis. PMID:22514522

  11. Exploring risk of experiencing intimate partner violence after HIV infection: a qualitative study among women with HIV attending postnatal services in Swaziland

    PubMed Central

    Mulrenan, Claire; Colombini, Manuela; Kikuvi, Joshua; Mayhew, Susannah H

    2015-01-01

    Objective To explore risks of experiencing intimate partner violence (IPV) after HIV infection among women with HIV in a postnatal care setting in Swaziland. Design A qualitative semistructured in-depth interview study, using thematic analysis with deductive and inductive coding, of IPV experiences after HIV infection extracted from service-integration interview transcripts. Setting Swaziland. Participants 19 women with HIV, aged 18–44, were purposively sampled for an in-depth interview about their experiences of services, HIV and IPV from a quantitative postnatal cohort participating in an evaluation of HIV and reproductive health services integration in Swaziland. Results Results indicated that women were at risk of experiencing IPV after HIV infection, with 9 of 19 disclosing experiences of physical violence and/or coercive control post-HIV. IPV was initiated through two key pathways: (1) acute interpersonal triggers (eg, status disclosure, mother-to-child transmission of HIV) and (2) chronic normative tensions (eg, fertility intentions, initiating contraceptives). Conclusions The results highlight a need to mitigate the risk of IPV for women with HIV in shorter and longer terms in Swaziland. While broader changes are needed to resolve gender disparities, practical steps can be institutionalised within health facilities to reduce, or avoid increasing, IPV pathways for women with HIV. These might include mutual disclosure between partners, greater engagement of Swazi males with HIV services, and promoting positive masculinities that support and protect women. Trial registration number NCT01694862. PMID:25976760

  12. Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality

    PubMed Central

    Dudok, Jacobus J.; Groffen, Alexander J. A.; Toonen, Ruud F. T.; Verhage, Matthijs

    2011-01-01

    The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT) promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival. PMID:22140524

  13. The effect of in vivo hydrocortisone administration on the labelling index and size of chromaffin tissue in the postnatal and adult mouse.

    PubMed Central

    Monkhouse, W S

    1986-01-01

    Hydrocortisone administration in vivo to neonatal mice for seven days led to a significant increase in both the size and the labelling index of extra-adrenal chromaffin tissue (as represented by the para-aortic body) of 8 days old mice. In untreated animals at this age, the para-aortic body was in most cases too small to obtain a valid labelling index. In the para-aortic bodies of 14 days old, 21 days old and adult mice, the extra-adrenal chromaffin tissue was too dispersed to obtain values for either volumetric analysis or labelling indices, and hydrocortisone was without significant effect in promoting a hyperplastic response. In the postnatal adrenal medulla at all ages studied, hydrocortisone had no effect on the medullary size or on the labelling indices of either adrenaline- or noradrenaline-storing cells, although it led to a marked diminution of adrenocortical volume. The relative proportion of adrenaline-storing cells increased between the values for 8 days old animals and those for adults; this was unaffected by hydrocortisone. The cortico-medullary ratio remained unchanged from the eighth postnatal day onwards. The results are discussed and related to those of other workers. It is suggested that factors as yet unknown might modulate the response to corticosteroids of developing intra- and extra-adrenal chromaffin tissue. Images Fig. 1 Fig. 2 PMID:3693040

  14. Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

    PubMed

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-02-14

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  15. 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.

  16. 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.

  17. Relationship of prenatal transportation stress with postnatal temperament of Brahman calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prenatal stress resulting from repeated transportation during gestation has been shown to increase postnatal adrenal responsiveness of calves to a stressor. The objective of the current experiment was to examine the relationship between prenatal stress and gestation length, calf birth weight, and su...

  18. Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells.

    PubMed

    Zhang, Zhaocheng; Nör, Felipe; Oh, Min; Cucco, Carolina; Shi, Songtao; Nör, Jacques E

    2016-06-01

    Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/β-catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, β-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/β-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587.

  19. The Long-Term Economic Impact of in Utero and Postnatal Exposure to Malaria

    ERIC Educational Resources Information Center

    Barreca, Alan I.

    2010-01-01

    I use an instrumental-variables identification strategy and historical data from the United States to estimate the long-term economic impact of in utero and postnatal exposure to malaria. My research design matches adults in the 1960 Decennial Census to the malaria death rate in their respective state and year of birth. To address potential…

  20. Evidence for Hippocampus-Dependent Contextual Learning at Postnatal Day 17 in the Rat

    ERIC Educational Resources Information Center

    Foster, Jennifer A.; Burman, Michael A.

    2010-01-01

    Long-term memory for fear of an environment (contextual fear conditioning) emerges later in development (postnatal day; PD 23) than long-term memory for fear of discrete stimuli (PD 17). As contextual, but not explicit cue, fear conditioning relies on the hippocampus; this has been interpreted as evidence that the hippocampus is not fully…

  1. Developmental schedule of the postnatal rat testis determined by flow cytometry.

    PubMed

    Malkov, M; Fisher, Y; Don, J

    1998-07-01

    Analysis of the biochemical events and the genes expressed at various postnatal developmental stages in the testis of mammals is of great importance for understanding spermatogenesis in general and meiosis in particular. A prerequisite for such an analysis is the characterization of a detailed developmental schedule of the postnatal testis. In this study we used four-parameter flow cytometry analysis to determine a detailed testicular developmental schedule in rats as compared to mice. A dot plot of forward-scatter/side-scatter of testicular cell suspensions from mature animals revealed 7 distinct subpopulations within the testis. These, when analyzed by fluorescence parameters, were divided into 4 levels of fluorescence: cells containing 4d DNA, 2d DNA, and 2 levels of haploid cells. Observing the acquisition pattern of these subpopulations during postnatal development, we were able to suggest the following developmental schedule for the rat. At postnatal Days 6-7, the testis contains somatic cells and spermatogonia cells only. By Days 13-14, leptotene spermatocytes appear; by Days 17-18, zygotene spermatocytes are present; by Days 19-20 and Days 22-23, early and late pachytene spermatocytes, respectively, are seen. Haploid round spermatids first appear at Days 24-25 and elongating spermatids by Days 30-31; by Day 36, elongated spermatozoa can be found.

  2. Postnatal changes of local neuronal circuits involved in activation of jaw-closing muscles.

    PubMed

    Inoue, Tomio; Nakamura, Shiro; Takamatsu, Junichi; Tokita, Kenichi; Gemba, Akiko; Nakayama, Kiyomi

    2007-04-01

    Feeding behaviour in mammals changes from suckling to mastication during postnatal development and the neuronal circuits controlling feeding behaviour should change in parallel to the development of orofacial structures. In this review we discuss the location of excitatory premotor neurons for jaw-closing motoneurons (JCMNs) and postnatal changes of excitatory synaptic transmission from the supratrigeminal region (SupV) to JCMNs. We show that neurons located in SupV and the reticular formation dorsal to the facial nucleus most likely excite JCMNs. Excitatory inputs from SupV to JCMNs are mediated by activation of glutamate and glycine receptors in neonatal rats, whereas glycinergic inputs from SupV to JCMNs become inhibitory with age. We also show that the incidence of post-spike afterdepolarization increases during postnatal development, whereas the amplitude and half-duration of the medium-duration afterhyperpolarization decrease with age. Such postnatal changes in synaptic transmission from SupV to JCMNs and membrane properties of JCMNs might be involved in the transition from suckling to mastication.

  3. In utero heat stress increases postnatal core body temperature in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In utero heat stress (IUHS) negatively impacts postnatal development, but how it alters future body temperature parameters and energetic metabolism is not well-understood. Objectives were to characterize future temperature indices and bioenergetic markers in pigs originating from differing in utero...

  4. Prenatal Maternal Reactivity to Infant Cries Predicts Postnatal Perceptions of Infant Temperament and Marriage Appraisal.

    ERIC Educational Resources Information Center

    Pedersen, Frank A.; And Others

    1996-01-01

    Examined cardiac response and ratings of subjective aversiveness to recordings of unfamiliar infant cries in 60 primiparous women at 32 weeks' gestation. Mothers who prenatally rated the crying recordings as more aversive postnatally described their infants as more fussy and unpredictable. Women who showed greater cardiac acceleration to the cries…

  5. NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain

    PubMed Central

    2011-01-01

    From an early postnatal period and throughout life there is a continuous production of olfactory bulb (OB) interneurons originating from neuronal precursors in the subventricular zone. To reach the OB circuits, immature neuroblasts migrate along the rostral migratory stream (RMS). In the present study, we employed cultured postnatal mouse forebrain slices and used lentiviral vectors to label neuronal precursors with GFP and to manipulate the expression levels of the Na-K-2Cl cotransporter NKCC1. We investigated the role of this Cl- transporter in different stages of postnatal neurogenesis, including neuroblast migration and integration in the OB networks once they have reached the granule cell layer (GCL). We report that NKCC1 activity is necessary for maintaining normal migratory speed. Both pharmacological and genetic manipulations revealed that NKCC1 maintains high [Cl-]i and regulates the resting membrane potential of migratory neuroblasts whilst its functional expression is strongly reduced at the time cells reach the GCL. As in other developing systems, NKCC1 shapes GABAA-dependent signaling in the RMS neuroblasts. Also, we show that NKCC1 controls the migration of neuroblasts in the RMS. The present study indeed indicates that the latter effect results from a novel action of NKCC1 on the resting membrane potential, which is independent of GABAA-dependent signaling. All in all, our findings show that early stages of the postnatal recruitment of OB interneurons rely on precise, orchestrated mechanisms that depend on multiple actions of NKCC1. PMID:21284844

  6. Solutions forgone? How health professionals frame the problem of postnatal depression.

    PubMed

    Lloyd, Beverley; Hawe, Penelope

    2003-11-01

    Our interest is in how particular solutions in postnatal depression have a tendency to be adopted at the expense of alternative solutions. One aspect of the answer may lie in how people in positions of authority think about problems. 'Framing' refers to the way particular causalities, consequences and moralities are contained within the ways in which people communicate concepts, in particular in language and in metaphor. Naming the way problems are framed and identifying alternative frames, (i.e., 'reframing') may provide an opportunity to set problems more effectively and to identify solutions that will solve the problem more effectively. A framing analysis was conducted, drawing on interviews with senior researchers, policy makers and practitioners in the field of postnatal depression. Seven principal ways in which the problem of postnatal depression was framed were illuminated. These fitted into three broad approaches to the problem: individual therapeutic approaches, social competence approaches and societal approaches. Participants in our study were comfortable and articulate in describing the problem of postnatal depression-whether they were focused on the individual or societal levels of analysis. However, they were less well versed and comfortable in discussing what they felt might be important social or societal-level solutions, lacking in both language and schema to do so. The history and hierarchy that is carried by people from the helping professions may be hindering new avenues to help mothers with new babies.

  7. Postnatal development of echolocation abilities in a bottlenose dolphin (Tursiops truncatus): temporal organization.

    PubMed

    Favaro, Livio; Gnone, Guido; Pessani, Daniela

    2013-03-01

    In spite of all the information available on adult bottlenose dolphin (Tursiops truncatus) biosonar, the ontogeny of its echolocation abilities has been investigated very little. Earlier studies have reported that neonatal dolphins can produce both whistles and burst-pulsed sounds just after birth and that early-pulsed sounds are probably a precursor of echolocation click trains. The aim of this research is to investigate the development of echolocation signals in a captive calf, born in the facilities of the Acquario di Genova. A set of 81 impulsive sounds were collected from birth to the seventh postnatal week and six additional echolocation click trains were recorded when the dolphin was 1 year old. Moreover, behavioral observations, concurring with sound production, were carried out by means of a video camera. For each sound we measured five acoustic parameters: click train duration (CTD), number of clicks per train, minimum, maximum, and mean click repetition rate (CRR). CTD and number of clicks per train were found to increase with age. Maximum and mean CRR followed a decreasing trend with dolphin growth starting from the second postnatal week. The calf's first head scanning movement was recorded 21 days after birth. Our data suggest that in the bottlenose dolphin the early postnatal weeks are essential for the development of echolocation abilities and that the temporal features of the echolocation click trains remain relatively stable from the seventh postnatal week up to the first year of life.

  8. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: postnatal evaluation

    EPA Science Inventory

    The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated ...

  9. 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.

  10. POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE

    EPA Science Inventory

    POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE.
    J J Diliberto', J T Hamm'.2, F McQuaid', and L S Birnbaum'. 'US EPA, ORD/NHEERL/ETD, RTP, NC; 2Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC.
    2,3,7,8-Tetrachlorodibenz...

  11. 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.

  12. 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.

  13. Changing numbers of neuronal and non-neuronal cells underlie postnatal brain growth in the rat

    PubMed Central

    Bandeira, Fabiana; Lent, Roberto; Herculano-Houzel, Suzana

    2009-01-01

    The rat brain increases >6× in mass from birth to adulthood, presumably through the addition of glial cells and increasing neuronal size, without the addition of neurons. To test this hypothesis, here we investigate quantitatively the postnatal changes in the total number of neuronal and non-neuronal cells in the developing rat brain, and examine how these changes correlate with brain growth. Total numbers of cells were determined with the isotropic fractionator in the brains of 53 Wistar rats, from birth to young adulthood. We find that at birth, >90% of the cells in the rat brain are neurons. Following a dormant period of ≈3 days after birth, the net number of neurons in the cerebral cortex, hippocampus, and remaining tissue (excluding cerebellum and olfactory bulb) doubles during the first week, then is reduced by 70% during the second postnatal week, concurrently with net gliogenesis. A second round of net addition of 6 million neurons is observed in the cerebral cortex over the following 2 weeks. During the first postnatal week, brain growth relates mainly to increased numbers of neurons of larger average size. In the second and third weeks, it correlates with increased numbers of non-neuronal cells that are smaller in size than the preexisting neurons. Postnatal rat brain development is thus characterized by dramatic changes in the cellular composition of the brain, whose growth is governed by different combinations of cell addition and loss, and changes in average cell size during the first months after birth. PMID:19666520

  14. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

    PubMed Central

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-01-01

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life. PMID:28216584

  15. Pre- and Postnatal Influences on Preschool Mental Health: A Large-Scale Cohort Study

    ERIC Educational Resources Information Center

    Robinson, Monique; Oddy, Wendy H.; Li, Jianghong; Kendall, Garth E.; de Klerk, Nicholas H.; Silburn, Sven R.; Zubrick, Stephen R.; Newnham, John P.; Stanley, Fiona J.; Mattes, Eugen

    2008-01-01

    Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western…

  16. Exposure to Lipopolysaccharide in Utero Alters the Postnatal Metabolic Response in Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal metabolic response to an LPS challenge in beef heifers. Pregnant crossbred cows (n = 50) were assigned to a prenatal immune stimulation (PIS; n = 25; administered 0.1 micrograms/kg BW LPS s...

  17. In Utero Exposure to Lipopolysaccharide Alters the Postnatal Acute Phase Response in Beef Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the potential effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers. Pregnant crossbred cows (n = 50) were separated into prenatal immune stimulation (PIS; n = 25; administered 0.1 microgr...

  18. ADVERSE PRE- AND POSTNATAL EVENTS REPORTED TO FDA IN ASSOCIATION WITH MATERNAL ATENOLOL TREATMENT IN PREGNANCY

    EPA Science Inventory

    Atenolol is a beta-adrenoreceptor blocker used for treatment of hypertension in pregnancy. This study evaluates the reporting frequency of adverse pre- and postnatal outcomes in a series of 70 cases of maternal exposure during gestation, derived from 140 reports to FDA with Ateno...

  19. 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

  20. Sensory and motor characterization in the postnatal valproate rat model of autism.

    PubMed

    Reynolds, Stacey; Millette, Alexandre; Devine, Darragh P

    2012-01-01

    Although autism is diagnosed according to three core features of social deficits, communication impairments, and repetitive or stereotyped behaviors, other behavioral features such as sensory and motor impairments are present in more than 70% of individuals with autism spectrum disorders (ASD). Exposure of rat pups to the teratogen valproate during sensitive periods of brain development has been shown to elicit behavioral features associated with autism diagnosis and has been proposed as a valid animal model of the disorder. The purpose of this study was to characterize sensory and motor performance in rats postnatally treated with valproate. Thirty-four rat pups were injected with either valproate (150 mg/kg) or saline on postnatal days 6-12. Auditory and tactile startle as well as auditory sensory gating was assessed during both the juvenile and adolescent stages of development; motor testing was conducted during late adolescence and included a sunflower seed eating task and a vermicelli handling task. Valproate-treated rats were underresponsive to auditory stimuli, showed deficits in auditory sensory gating, and demonstrated impairments in motor speed and performance. These findings suggest that postnatal valproate treatment elicits sensory and motor features often seen in individuals with ASD. Further, the hyposensitivity seen in postnatally valproate-treated rats contrasted with hypersensitivity previously reported in prenatally valproate-exposed rats. This suggests that timing of teratogenic exposure during early brain development may be important to consider when investigating the neurobiological basis of sensorimotor impairments in ASD.

  1. A BIOASSAY THAT IDENTIFIES POSTNATAL FUNCTIONAL DEFICITS IN MICE PRENATALLY EXPOSED TO XENOBIOTICS

    EPA Science Inventory

    Experimental strategies to evaluate adverse postnatal effects due to prenatal exposure exist for many organ systems. Often, however, there is insufficient information to suggest that a particular organ system(s) may be sensitive to the test agent. A single bioassay to identify ...

  2. Non-School Influences and Educational Disadvantage: Pre and Post-natal Nutritional Deprivation

    ERIC Educational Resources Information Center

    Doll, Russell C.

    1973-01-01

    Deals with pre and post-natal malnutrition and its possible influence on the child, focusing on these points: How wide-spread and severe is the malnutrition? What might be the effects of the malnutrition at certain critical points in development? (Author/JM)

  3. Hominins do not share a common postnatal facial ontogenetic shape trajectory.

    PubMed

    Cobb, S N; O'Higgins, P

    2004-05-15

    This paper examines the hypothesis raised by recent studies that postnatal trajectories of shape change in the facial skeleton are parallel between, at least, chimpanzees, modern humans and also fossil hominins, specifically australopithecines and possibly Neanderthals. In contrast, other studies point to divergences in postnatal shape trajectories within diverse groups of primates. As such there is some debate regarding the relative contributions of pre and postnatal ontogeny to adult morphological differences. This paper presents a series of geometric morphometric studies of the ontogeny of facial shape in hominins with the specific aim of resolving these issues. The results indicate that many differences in facial shape between hominins are established prenatally, however highly significant divergences of postnatal facial ontogeny are found among living hominins. Our studies point to possible differences between the shape ontogeny of the Australopithecus africanus face and that of African apes on the one hand and humans on the other. However, sampling experiments indicate that the small sample size of available specimens of A. africanus does not permit any conclusions to be drawn regarding comparative shape ontogeny of the face.

  4. Primary Postnatal Dorsal Root Ganglion Culture from Conventionally Slaughtered Calves

    PubMed Central

    Fadda, A.; Bärtschi, M.; Hemphill, A.; Widmer, H. R.; Zurbriggen, A.; Perona, P.; Vidondo, B.; Oevermann, A.

    2016-01-01

    Neurological disorders in ruminants have an important impact on veterinary health, but very few host-specific in vitro models have been established to study diseases affecting the nervous system. Here we describe a primary neuronal dorsal root ganglia (DRG) culture derived from calves after being conventionally slaughtered for food consumption. The study focuses on the in vitro characterization of bovine DRG cell populations by immunofluorescence analysis. The effects of various growth factors on neuron viability, neurite outgrowth and arborisation were evaluated by morphological analysis. Bovine DRG neurons are able to survive for more than 4 weeks in culture. GF supplementation is not required for neuronal survival and neurite outgrowth. However, exogenously added growth factors promote neurite outgrowth. DRG cultures from regularly slaughtered calves represent a promising and sustainable host specific model for the investigation of pain and neurological diseases in bovines. PMID:27936156

  5. Oral antibiotics increase blood neutrophil maturation and reduce bacteremia and necrotizing enterocolitis in the immediate postnatal period of preterm pigs.

    PubMed

    Nguyen, Duc Ninh; Fuglsang, Eva; Jiang, Pingping; Birck, Malene M; Pan, Xiaoyu; Kamal, Shamrulazhar B S; Pors, Susanne E; Gammelgaard, Pernille L; Nielsen, Dennis S; Thymann, Thomas; Levy, Ofer; Frøkiær, Hanne; Sangild, Per T

    2016-01-01

    Immature immunity may predispose preterm neonates to infections and necrotizing enterocolitis (NEC). Intravenous antibiotics are frequently given to prevent and treat sepsis, while oral antibiotics are seldom used. We hypothesized that oral antibiotics promote maturation of systemic immunity and delay gut bacterial colonization and thereby protect preterm neonates against both NEC and bacteremia in the immediate postnatal period. Preterm pigs were given formula and administered saline (CON) or broad-spectrum antibiotics orally (ORA) or systemically (SYS) for 5 d after birth. Temporal changes in blood parameters and bacterial composition in the intestine, blood and immune organs were analyzed. Newborn preterm pigs had few blood neutrophils and a high frequency of progenitor cells. Neutrophils gradually matured after preterm birth with increasing CD14 and decreasing CD172a expressions. Preterm neutrophil and monocyte TLR2 expression and TLR2-mediated blood cytokine responses were low relative to adults. ORA pigs showed enhanced blood neutrophil maturation with reduced cell size and CD172a expression. Only ORA pigs, but not SYS pigs, were protected from a high density of gut Gram-positive bacteria, high gut permeability, Gram-positive bacteremia and NEC. Neonatal oral antibiotics may benefit mucosal and systemic immunity via delayed gut colonization and enhanced blood neutrophil maturation just after preterm birth.

  6. Atoh1 Directs the Formation of Sensory Mosaics and Induces Cell Proliferation in the Postnatal Mammalian Cochlea In Vivo

    PubMed Central

    Kelly, Michael C.; Chang, Qing; Pan, Alex; Lin, Xi; Chen, Ping

    2012-01-01

    Hearing impairment due to the loss of sensory hair cells is permanent in humans. Considerable interest targets the hair cell differentiation factor Atoh1 as a potential tool with which to promote hair cell regeneration. We generated a novel mouse model to direct the expression of Atoh1 in a spatially and temporally specific manner in the postnatal mammalian cochlea to determine the competency of various types of cochlear epithelial cells for hair cell differentiation. Atoh1 can generate cells in young animals with morphological, molecular, and physiological properties reminiscent of hair cells.This competency is cell type specific and progressively restricted with age. Significantly, Atoh1 induces ectopic sensory patches through Notch signaling to form a cellular mosaic similar to the endogenous sensory epithelia and expansion of the sensory mosaic through the conversion of supporting cells and nonautonomous supporting cell production. Furthermore, Atoh1 also activates proliferation within the normally postmitotic cochlear epithelium. These results provide insight into the potential and limitations of Atoh1-mediated hair cell regeneration. PMID:22573692

  7. 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.

  8. Role of Neurotrophins on Postnatal Neurogenesis in the Thalamus: Prenatal Exposure to Ethanol

    PubMed Central

    Mooney, Sandra M.; Miller, Michael W.

    2011-01-01

    A second wave of neuronal generation occurs in the ventrobasal nucleus of the rat thalamus (VB) during the first three postnatal weeks. The present study tested the hypotheses (1) that postnatal neurogenesis in the VB is neurotrophin-regulated and (2) that ethanol-induced changes in this proliferation are mediated by neurotrophins. The first studies examined the effects of neurotrophins on the numbers of cycling cells in ex vivo preparations of the VB from three-day-old rats. The proportion of cycling (Ki-67-positive) VB cells was higher in cultured thalamic slices treated with neurotrophins than in controls. Interestingly, this increase occurred with nerve growth factor (NGF) alone or with a combination of NGF and brain-derived neurotrophic factor (BDNF), but not with BDNF alone. Based on these data, the VBs from young offspring of pregnant rats fed an ethanol-containing or an isocaloric non-alcoholic liquid diet were examined between postnatal day (P) 1 and P31. Studies used enzyme-linked immunosorbent assays and immunoblots to explore the effects of ethanol on the expression of neurotrophins, their receptors, and representative signaling proteins. Ethanol altered the expression of neurotrophins and receptors throughout the first postnatal month. Expression of NGF increased, but there was no change in the expression of BDNF. The high affinity receptors (TrkA and TrkB) were unchanged but ethanol decreased expression of the low affinity receptor, p75. One downstream signaling protein, extracellular signal-regulated kinase (ERK), decreased but Akt expression was unchanged. Thus, postnatal cell proliferation in the VB of young rat pups is neurotrophin-responsive and is affected by ethanol. PMID:21277941

  9. Postnatal dexamethasone-induced programmed hypertension is related to the regulation of melatonin and its receptors.

    PubMed

    Chang, Hsin-Yu; Tain, You-Lin

    2016-04-01

    Adulthood hypertension can be programmed by glucocorticoid exposure in early life. We found that maternal melatonin therapy prevents postnatal dexamethasone (DEX)-induced programmed hypertension. Melatonin acts through specific receptors, including MT1 and MT2 membrane receptors, and retinoid related orphan nuclear receptors of the RZR/ROR family. Thus we tested whether postnatal DEX-induced hypertension is related to changes of melatonin receptors in the kidney and heart, which was preserved by maternal melatonin therapy. Male neonates were assigned to four groups (n=6-8/group): control, DEX, control+melatonin (MEL), and DEX+MEL. Male rat pups were injected i.p. with DEX on d 1 (0.5 mg/kg BW), d 2 (0.3 mg/kg BW), and d 3 (0.1 mg/kg BW) after birth. Melatonin was administered in drinking water (0.01%) during the lactation period. We found DEX group developed hypertension at 16 weeks of age, which melatonin therapy prevented. Postnatal DEX treatment increased mRNA expression of MT1 and MT2, while decreased RORα and RZRβ in the kidney. These changes were prevented by melatonin therapy. Postnatal DEX decreased protein level of MT2 in the kidney, which was attenuated by melatonin therapy. Renal protein level of RORα was higher in DEX+MEL group compared to control and DEX group. Renal melatonin level was higher in the MEL and DEX+MEL groups compared to control. We concluded that melatonin therapy has long-term protection on postnatal DEX-induced programmed hypertension, which is associated with regulation on melatonin receptors in the kidney. Our findings would offer potential therapeutic approaches to prevent programmed hypertension in premature baby receiving glucocorticoids.

  10. Expression of Npas4 mRNA in Telencephalic Areas of Adult and Postnatal Mouse Brain

    PubMed Central

    Damborsky, Joanne C.; Slaton, G. Simona; Winzer-Serhan, Ursula H.

    2015-01-01

    The transcription factor neuronal PAS domain-containing protein 4 (Npas4) is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON), piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu), septum and basolateral amygdala nucleus (BLA), basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5), transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission. PMID:26633966

  11. 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

  12. 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.

  13. Correction of murine hemoglobinopathies by prenatal tolerance induction and postnatal nonmyeloablative allogeneic BM transplants.

    PubMed

    Peranteau, William H; Hayashi, Satoshi; Abdulmalik, Osheiza; Chen, Qiukan; Merchant, Aziz; Asakura, Toshio; Flake, Alan W

    2015-09-03

    Sickle cell disease (SCD) and thalassemias (Thal) are common congenital disorders, which can be diagnosed early in gestation and result in significant morbidity and mortality. Hematopoietic stem cell transplantation, the only curative therapy for SCD and Thal, is limited by the absence of matched donors and treatment-related toxicities. In utero hematopoietic stem cell transplantation (IUHCT) is a novel nonmyeloablative transplant approach that takes advantage of the immunologic immaturity and normal developmental properties of the fetus to achieve mixed allogeneic chimerism and donor-specific tolerance (DST). We hypothesized that a combined strategy of IUHCT to induce DST, followed by postnatal nonmyeloablative same donor "booster" bone marrow (BM) transplants in murine models of SCD and Thal would result in high levels of allogeneic engraftment and donor hemoglobin (Hb) expression with subsequent phenotypic correction of SCD and Thal. Our results show that: (1) IUHCT is associated with DST and low levels of allogeneic engraftment in the murine SCD and Thal models; (2) low-level chimerism following IUHCT can be enhanced to high-level chimerism and near complete Hb replacement with normal donor Hb with this postnatal "boosting" strategy; and (3) high-level chimerism following IUHCT and postnatal "boosting" results in phenotypic correction in the murine Thal and SCD models. This study supports the potential of IUHCT, combined with a postnatal nonmyelablative "boosting" strategy, to cure Thal and SCD without the toxic conditioning currently required for postnatal transplant regimens while expanding the eligible transplant patient population due to the lack of a restricted donor pool.

  14. Placental cortisol and cord serum IGFBP-2 concentrations are important determinants of postnatal weight gain.

    PubMed

    Street, M E; Smerieri, A; Petraroli, A; Cesari, S; Viani, I; Garrubba, M; Rossi, M; Bernasconi, S

    2012-01-01

    There is a need to identify simple biochemical markers at birth that may predict subjects at risk of growth failure and metabolic complications in later life. Limited research to date has been performed on relationships of specific biochemical determinants at birth with postnatal weight gain and growth. We proposed to establish whether placental cortisol and IL-6 concentrations and cord serum IGF-II and IGFBP-2 concentrations influenced postnatal growth. We followed up from pregnancy 23 IUGR and 37 AGA subjects, and determined placental cortisol and IL-6 concentrations, and cord serum IGF-II, and IGFBP-2 concentrations at birth. We obtained height and weight measurements at 3, 6, 12, 24 months and 5 years of age in 20 IUGR and 15 AGA subjects of comparable gestational age. A multiple linear regression model was designed to establish the effect of the placental and cord serum peptides on postnatal linear growth and weight gain. All IUGR subjects had catch-up growth before 2 years of age. Placental cortisol concentration correlated positively with weight gain during the first 5 years of postnatal growth (P<0.05). Subjects with the highest placental cortisol concentrations were those who showed a greater increase in weight. Cord serum IGFBP-2 concentrations correlated positively with weight gain throughout the 5 year observation period (P:0.003). The subjects with the highest concentrations showed a greater weight gain. Placental cortisol and cord serum IGFBP-2 concentrations were related to postnatal weight gain, suggesting that the fetal environment has long-term effects on growth.

  15. Expression Pattern of Thyroid Hormone Transporters in the Postnatal Mouse Brain

    PubMed Central

    Müller, Julia; Heuer, Heike

    2014-01-01

    For a comprehensive description of the tissue-specific thyroidal state under normal as well as under pathophysiological conditions it is of utmost importance to include thyroid hormone (TH) transporters in the analysis as well. The current knowledge of the cell-specific repertoire of TH transporters, however, is still rather limited, although several TH transporting proteins have been identified. Here, we describe the temporal and spatial distribution pattern of the most prominent TH transporters in the postnatal mouse brain. For that purpose, we performed radioactive in situ hybridization studies in order to analyze the cellular mRNA expression pattern of the monocarboxylate transporters Mct8 and Mct10, the L-type amino acid transporters Lat1 and Lat2 as well as the organic anion transporting peptide Oatp1c1 at different postnatal time points. Highest TH transporter expression levels in the CNS were observed at postnatal day 6 and 12, while hybridization signal intensities visibly declined after the second postnatal week. The only exception was Mct10 for which the strongest signals could be observed in white matter regions at postnatal day 21 indicating that this transporter is preferentially expressed in mature oligodendrocytes. Whereas Mct8 and Lat2 showed an overlapping neuronal mRNA expression pattern in the cerebral cortex, hippocampus, and in the hypothalamus, Oatp1c1 and Lat1 specific signals were most prominent in capillary endothelial cells throughout the CNS. In the choroid plexus, expression of three transporters (Mct8, Lat2, and Oatp1c1) could be detected, whereas in other brain areas (e.g., striatum, thalamus, and brain stem nuclei) only one of the transporter candidates appeared to be present. Overall, our study revealed a distinct mRNA distribution pattern for each of the TH transporter candidates. Further studies will reveal to which extent these transporters contribute to the cell-specific TH uptake and efflux in the mouse CNS. PMID:24994998

  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. Neonatal pain in relation to postnatal growth in infants born very preterm.

    PubMed

    Vinall, Jillian; Miller, Steven P; Chau, Vann; Brummelte, Susanne; Synnes, Anne R; Grunau, Ruth E

    2012-07-01

    Procedural pain is associated with poorer neurodevelopment in infants born very preterm (≤ 32 weeks gestational age), however, the etiology is unclear. Animal studies have demonstrated that early environmental stress leads to slower postnatal growth; however, it is unknown whether neonatal pain-related stress affects postnatal growth in infants born very preterm. The aim of this study was to examine whether greater neonatal pain (number of skin-breaking procedures adjusted for medical confounders) is related to decreased postnatal growth (weight and head circumference [HC] percentiles) early in life and at term-equivalent age in infants born very preterm. Participants were n=78 preterm infants born ≤ 32 weeks gestational age, followed prospectively since birth. Infants were weighed and HC measured at birth, early in life (median: 32 weeks [interquartile range 30.7-33.6]) and at term-equivalent age (40 weeks [interquartile range 38.6-42.6]). Weight and HC percentiles were computed from sex-specific British Columbia population-based data. Greater neonatal pain predicted lower body weight (Wald χ(2)=7.36, P=0.01) and HC (Wald χ(2)=4.36, P=0.04) percentiles at 32 weeks postconceptional age, after adjusting for birth weight percentile and postnatal risk factors of illness severity, duration of mechanical ventilation, infection, and morphine and corticosteroid exposure. However, later neonatal infection predicted lower weight percentile at term (Wald χ(2)=5.09, P=0.02). Infants born very preterm undergo repetitive procedural pain during a period of physiological immaturity that appears to impact postnatal growth, and may activate a downstream cascade of stress signaling that affects later growth in the neonatal intensive care unit.

  18. Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

    PubMed Central

    2009-01-01

    Background Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia. Objective To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury. Methods 129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (VT) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with VT 8 mL/kg and PEEP 5 cmH20 for 2 h 45 min. Results High VT ventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids. Conclusions Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury. PMID:20003512

  19. Sex and Tissue Specificity of Peg3 Promoters

    PubMed Central

    Perera, Bambarendage P. U.; Kim, Joomyeong

    2016-01-01

    The expression of mouse Peg3 (Paternally expressed gene 3) is driven by 4 promoters, including its main and three alternative promoters. The sexual, temporal and spatial specificity of these promoters was characterized in the current study. According to the results, the main promoter displays ubiquitous expression patterns throughout different stages and tissues. In contrast, the expression of Peg3 driven by the alternative promoter U2 was detected mainly in muscle and skin, but not in brain, starting from the late embryonic stage, revealing its tissue and stage specificity. The expression levels of both the main and U2 promoters are also sexually biased: the levels in females start higher but become lower than those in males during early postnatal stages. As an imprinted locus, the paternal alleles of these promoters are active whereas the maternal alleles are silent. Interestingly, deletion of the repressed maternal allele of the main promoter has an unusual effect on the opposite paternal allele, causing the up-regulation of both the main and U2 promoters. Overall, the promoters of Peg3 derive sexually biased and tissue-specific expression patterns. PMID:27711129

  20. Impact of a Manualized Multifocal Perinatal Home-Visiting Program Using Psychologists on Postnatal Depression: The CAPEDP Randomized Controlled Trial

    PubMed Central

    Dugravier, Romain; Tubach, Florence; Saias, Thomas; Guedeney, Nicole; Pasquet, Blandine; Purper-Ouakil, Diane; Tereno, Susana; Welniarz, Bertrand; Matos, Joana

    2013-01-01

    Context Postnatal maternal depression (PND) is a significant risk factor for infant mental health. Although often targeted alongside other factors in perinatal home-visiting programs with vulnerable families, little impact on PND has been observed. Objective This study evaluates the impact on PND symptomatology of a multifocal perinatal home-visiting intervention using psychologists in a sample of women presenting risk factors associated with infant mental health difficulties. Methods 440 primiparous women were recruited at their seventh month of pregnancy. All were future first-time mothers, under 26, with at least one of three additional psychosocial risk factors: low educational level, low income, or planning to raise the child without the father. The intervention consisted of intensive multifocal home visits through to the child’s second birthday. The control group received care as usual. PND symptomatology was assessed at baseline and three months after birth using the Edinburgh Postnatal Depression Scale (EPDS). Results At three months postpartum, mean (SD) EPDS scores were 9.4 (5.4) for the control group and 8.6 (5.4) for the intervention group (p = 0.18). The difference between the mean EPDS scores was 0.85 (95% CI: 0.35; 1.34). The intervention group had significantly lower EPDS scores than controls in certain subgroups: women with few depressive symptoms at inclusion (EPDS <8): difference = 1.66 (95%CI: 0.17; 3.15), p = 0.05, adjusted for baseline EPDS score), women who were planning to raise the child with the child’s father: difference = 1.45 (95%CI: 0.27; 2.62), p = 0.04 (adjusted); women with a higher educational level: difference = 1.59 (95%CI: 0.50; 2.68) p = 0.05 (adjusted). Conclusion CAPEDP failed to demonstrate an overall impact on PND. However, post-hoc analysis reveals the intervention was effective in terms of primary prevention and in subgroups of women without certain risk factors. Effective overall reduction

  1. Creb1-Mecp2-mCpG Complex Transactivates Postnatal Murine Neuronal Glucose Transporter Isoform 3 Expression

    PubMed Central

    Chen, Yongjun; Shin, Bo-Chul; Thamotharan, Shanthie

    2013-01-01

    The murine neuronal facilitative glucose transporter isoform 3 (Glut3) is developmentally regulated, peaking in expression at postnatal day (PN)14. In the present study, we characterized a canonical CpG island spanning the 5′-flanking region of the glut3 gene. Methylation-specific PCR and bisulfite sequencing identified methylation of this CpG (mCpG) island of the glut3 gene, frequency of methylation increasing 2.5-fold with a 1.6-fold increase in DNA methyl transferase 3a concentrations noted with advancing postnatal age (PN14 vs PN3). 5′-flanking region of glut3-luciferase reporter transient transfection in HT22 hippocampal neurons demonstrated that mCpGs inhibit glut3 transcription. Contrary to this biological function, glut3 expression rises synchronously with mCpGs in PN14 vs PN3 neurons. Chromatin immunoprecipitation (IP) revealed that methyl-CpG binding protein 2 (Mecp2) bound the glut3-mCpGs. Depending on association with specific coregulators, Mecp2, a dual regulator of gene transcription, may repress or activate a downstream gene. Sequential chromatin IP uncovered the glut3-mCpGs to bind Mecp2 exponentially upon recruitment of Creb1 rather than histone deacetylase 1. Co-IP and coimmunolocalization confirmed that Creb1 associated with Mecp2 and cotransfection with glut3-mCpG in HT22 cells enhanced glut3 transcription. Separate 5-aza-2′-deoxycytidine pretreatment or in combination with trichostatin A reduced mCpG and specific small interference RNAs targeting Mecp2 and Creb1 separately or together depleting Mecp2 and/or Creb1 binding of glut3-mCpGs reduced glut3 expression in HT22 cells. We conclude that Glut3 is a methylation-sensitive neuronal gene that recruits Mecp2. Recruitment of Creb1-Mecp2 by glut3-mCpG contributes towards transactivation, formulating an escape from mCpG-induced gene suppression, and thereby promoting developmental neuronal glut3 gene transcription and expression. PMID:23493374

  2. Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling

    PubMed Central

    Menéndez-Gutiérrez, María P.; Rőszer, Tamás; Fuentes, Lucía; Núñez, Vanessa; Escolano, Amelia; Redondo, Juan Miguel; De Clerck, Nora; Metzger, Daniel; Valledor, Annabel F.; Ricote, Mercedes

    2015-01-01

    Osteoclasts are bone-resorbing cells that are important for maintenance of bone remodeling and mineral homeostasis. Regulation of osteoclast differentiation and activity is important for the pathogenesis and treatment of diseases associated with bone loss. Here, we demonstrate that retinoid X receptors (RXRs) are key elements of the transcriptional program of differentiating osteoclasts. Loss of RXR function in hematopoietic cells resulted in formation of giant, nonresorbing osteoclasts and increased bone mass in male mice and protected female mice from bone loss following ovariectomy, which induces osteoporosis in WT females. The increase in bone mass associated with RXR deficiency was due to lack of expression of the RXR-dependent transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MAFB) in osteoclast progenitors. Evaluation of osteoclast progenitor cells revealed that RXR homodimers directly target and bind to the Mafb promoter, and this interaction is required for proper osteoclast proliferation, differentiation, and activity. Pharmacological activation of RXRs inhibited osteoclast differentiation due to the formation of RXR/liver X receptor (LXR) heterodimers, which induced expression of sterol regulatory element binding protein-1c (SREBP-1c), resulting in indirect MAFB upregulation. Our study reveals that RXR signaling mediates bone homeostasis and suggests that RXRs have potential as targets for the treatment of bone pathologies such as osteoporosis. PMID:25574839

  3. Low-intensity and moderate exercise training improves autonomic nervous system activity imbalanced by postnatal early overfeeding in rats

    PubMed Central

    2014-01-01

    Background Postnatal early overfeeding and physical inactivity are serious risk factors for obesity. Physical activity enhances energy expenditure and consumes fat stocks, thereby decreasing body weight (bw). This study aimed to examine whether low-intensity and moderate exercise training in different post-weaning stages of life is capable of modulating the autonomic nervous system (ANS) activity and inhibiting perinatal overfeeding-induced obesity in rats. Methods The obesity-promoting regimen was begun two days after birth when the litter size was adjusted to 3 pups (small litter, SL) or to 9 pups (normal litter, NL). The rats were organized into exercised groups as follows: from weaning until 90-day-old, from weaning until 50-day-old, or from 60- until 90-days-old. All experimental procedures were performed just one day after the exercise training protocol. Results The SL-no-exercised (SL-N-EXE) group exhibited excess weight and increased fat accumulation. We also observed fasting hyperglycemia and glucose intolerance in these rats. In addition, the SL-N-EXE group exhibited an increase in the vagus nerve firing rate, whereas the firing of the greater splanchnic nerve was not altered. Independent of the timing of exercise and the age of the rats, exercise training was able to significantly blocks obesity onset in the SL rats; even SL animals whose exercise training was stopped at the end of puberty, exhibited resistance to obesity progression. Fasting glycemia was maintained normal in all SL rats that underwent the exercise training, independent of the period. These results demonstrate that moderate exercise, regardless of the time of onset, is capable on improve the vagus nerves imbalanced tonus and blocks the onset of early overfeeding-induced obesity. Conclusions Low-intensity and moderate exercise training can promote the maintenance of glucose homeostasis, reduces the large fat pad stores associated to improvement of the ANS activity in adult rats that were

  4. Postnatal alterations of GABA receptor profiles in the rat superior colliculus.

    PubMed

    Clark, S E; Garret, M; Platt, B

    2001-01-01

    Midbrain sections taken from Sprague-Dawley rats of varying ages within the first four postnatal weeks were used to determine, immunocytochemically, putative changes of GABA(A) receptor beta2/3 subunits, GABA(B) receptor (R1a and R1b splice variants), and GABA(C) receptor rho1 subunit expression and distribution in the superficial, visual layers of the superior colliculus. Immunoreactivity for the GABA(A) receptor beta2/3 subunits was found in the superficial grey layer from birth. The labelling changed with age, with an overall continuous reduction in the number of cells labelled and a significant increase in the labelling intensity distribution (neuropil vs soma). Further analysis revealed an initial increase in the labelling intensity between postnatal days 0 and 7 in parallel with an overall reduction of labelled neurones. This was followed by a significant decrease in labelling intensity distribution between postnatal days 7 and 16, and a subsequent increase in intensity between postnatal days 16 and 28. The labelling profiles for GABA(B) receptors (R1a and R1b splice variants) and GABA(C) receptors (rho1 subunit) showed similar patterns. Both receptors could be found in the superficial layers of the superior colliculus from birth, and the intensity and distribution of labelling remained constant during the first postnatal month. However, the cell body count showed a significant decrease between postnatal days 7 and 16. These changes may be related to the time-point of eye opening, which occurred approximately two weeks after birth. For all three receptor types, the cell body count remained constant after postnatal day 16. By four weeks of age, there was no significant difference between the cell numbers obtained for the different receptors. Both GABA itself and neurofilament labelling were also obtained in the superficial superior colliculus at birth. Neurofilament, although found at birth, showed very little ordered arrangement until 16days after birth. When

  5. 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

  6. Predictors of postnatal mother-infant bonding: the role of antenatal bonding, maternal substance use and mental health.

    PubMed

    Rossen, Larissa; Hutchinson, Delyse; Wilson, Judy; Burns, Lucy; A Olsson, Craig; Allsop, Steve; J Elliott, Elizabeth; Jacobs, Sue; Macdonald, Jacqueline A; Mattick, Richard P

    2016-08-01

    The emotional bond that a mother feels towards her baby is critical to social, emotional and cognitive development. Maternal health and wellbeing through pregnancy and antenatal bonding also play a key role in determining bonding postnatally, but the extent to which these relationships may be disrupted by poor mental health or substance use is unclear. This study aimed to examine the extent to which mother-fetal bonding, substance use and mental health through pregnancy predicted postnatal mother-infant bonding at 8 weeks. Participants were 372 women recruited from three metropolitan hospitals in Australia. Data was collected during trimesters one, two and three of pregnancy and 8 weeks postnatal using the Maternal Antenatal Attachment Scale (MAAS), Maternal Postnatal Attachment Scale (MPAS), the Edinburgh Antenatal and Postnatal Depression Scale (EPDS), the Depression and Anxiety Scales (DASS-21), frequency and quantity of substance use (caffeine, alcohol and tobacco) as well as a range of demographic and postnatal information. Higher antenatal bonding predicted higher postnatal bonding at all pregnancy time-points in a fully adjusted regression model. Maternal depressive symptoms in trimesters two and three and stress in trimester two were inversely related to poorer mother-infant bonding 8 weeks postnatally. This study extends previous work on the mother's felt bond to her developing child by drawing on a large sample of women and documenting the pattern of this bond at three time points in pregnancy and at 8 weeks postnatally. Utilising multiple antenatal waves allowed precision in isolating the relationships in pregnancy and at key intervention points. Investigating methods to enhance bonding and intervene in pregnancy is needed. It is also important to assess maternal mental health through pregnancy.

  7. Differential regulation of GLT-1/EAAT2 gene expression by NF-κB and N-myc in male mouse brain during postnatal development.

    PubMed

    Gupta, Rajaneesh Kumar; Prasad, S

    2014-01-01

    The synaptic glutamate level homeostasis is mainly maintained by the astrocytes membrane bound glutamate transporter type-1 (GLT-1/EAAT2). Alterations in its expression during development and aging and the underlying mechanisms are not well studied. Here, we report that NF-κB interaction was highest in both cerebral and cerebellar cortices at day 15 when compared with that at day 0 during development, and it further declined significantly in day 45, and remained unchanged in 20 and 70 weeks mice. On the other hand, N-myc interaction was highest at 0 day which significantly declined at 15-day and interestingly remained unaltered at later ages in both the cortices. This age dependent reciprocal pattern of NF-κB and N-myc interactions with their cognate GLT-1 promoter sequences was further correlated with GLT-1 protein and transcript levels. We found that higher NF-κB interaction with its cognate GLT-1 promoter sequences correlates with up-regulation whereas the higher N-myc interaction correlates with down-regulation of GLT-1 expression during postnatal developmental age up to 15 day, however, such phenomenon was not found in the higher ages from day 45 to 70 weeks. Thus our data suggests a postnatal development- and age dependent differential interaction of transcription factors NF-κB and N-myc to their respective sequences and they act as positive and negative regulator, respectively of GLT-1 gene expression in the brain during early developmental period in both cerebral and cerebellar cortices which might be different in aging of mice.

  8. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.

    PubMed

    El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2015-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.

  9. Liquid flow across the epithelium of the artificially perfused lung of fetal and postnatal sheep.

    PubMed Central

    Ramsden, C A; Markiewicz, M; Walters, D V; Gabella, G; Parker, K A; Barker, P M; Neil, H L

    1992-01-01

    1. The lungs of five fetal (133-140 days gestation) and thirty-four postnatal (2-240 days) sheep were artificially perfused in situ with warmed and oxygenated sheep blood. In postnatal animals the airspace of the lung was filled with liquid similar in composition to fetal lung liquid. In fetal and postnatal animals luminal liquid volume was measured by the impermeant tracer technique. 2. Under resting conditions the pulmonary epithelium of fetal animals secreted liquid at a mean (+/- S.E.M.) rate of 2.0 (+/- 0.4) ml (kg body weight)-1 h-1, those of postnantal animals absorbed liquid at -1.8 (+/- 0.2) ml (kg body weight)-1 h-1. 3. Addition of 2,4-dinitrophenol to achieve a concentration of 1.5 x 10(-3) M in the perfusing blood in postnatal animals caused complete cessation of liquid absorption. 4. Light and electron microscopic examination of the lung after periods of up to 6 h of artificial perfusion showed no evidence of epithelial damage. From 3 h onwards, liquid accumulation was evident in the perivascular spaces. 5. Addition of adrenaline to the perfusate in fetal animals caused absorption of liquid to occur at a mean rate of -2.9 (+/- 1.3) ml (kg body weight)-1 h-1. In postnatal animals adrenaline caused the rate of liquid absorption to increase from a mean rate of -1.4 (+/- 0.2) to -2.2 (+/- 0.3) ml (kg body weight)-1 h-1. 6. In the fetus addition of amiloride (0.8 x 10(-4) M) to the luminal fluid blocked adrenaline-induced liquid absorption and caused secretion to occur at 1.3 (+/- 0.3) ml (kg body weight)-1 h-1. 7. In postnatal animals the response to amiloride was age dependent. In newborn lambs (2-14 days) amiloride blocked liquid absorption and caused secretion of liquid to occur in seven out of eight animals at a mean rate of 0.9 (+/- 0.3) ml (kg body weight)-1 h-1 (n = 8). In older animals (15-240 days) the characteristic response to amiloride was slowing of the rate of liquid absorption (mean rate of absorption,-0.2 (+/- 0.09) ml (kg body weight)-1 h

  10. Are portable bladder scanning and real-time ultrasound accurate measures of bladder volume in postnatal women?

    PubMed

    Mathew, S; Horne, A W; Murray, L S; Tydeman, G; McKinley, C A

    2007-08-01

    Real-time ultrasound and portable bladder scanners are commonly used instead of catheterisation to determine bladder volumes in postnatal women but it is not known whether these are accurate. Change in bladder volumes measured by ultrasound and portable scanners were compared with actual voided volume (VV) in 100 postnatal women. The VV was on average 41 ml (CI 29 - 54 ml) higher than that measured by ultrasound, and 33 ml (CI 17 - 48 ml) higher than that measured by portable scanners. Portable scanner volumes were 9 ml (CI -8 - 26 ml) higher than those measured by ultrasound. Neither method is an accurate tool for detecting bladder volume in postnatal women.

  11. 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.

  12. Generation of murine sympathoadrenergic progenitor-like cells from embryonic stem cells and postnatal adrenal glands.

    PubMed

    Saxena, Shobhit; Wahl, Joachim; Huber-Lang, Markus S; Stadel, Dominic; Braubach, Peter; Debatin, Klaus-Michael; Beltinger, Christian

    2013-01-01

    Sympathoadrenergic progenitor cells (SAPs) of the peripheral nervous system (PNS) are important for normal development of the sympathetic PNS and for the genesis of neuroblastoma, the most common and often lethal extracranial solid tumor in childhood. However, it remains difficult to isolate sufficient numbers of SAPs for investigations. We therefore set out to improve generation of SAPs by using two complementary approaches, differentiation from murine embryonic stem cells (ESCs) and isolation from postnatal murine adrenal glands. We provide evidence that selecting for GD2 expression enriches for ESC-derived SAP-like cells and that proliferating SAP-like cells can be isolated from postnatal adrenal glands of mice. These advances may facilitate investigations about the development and malignant transformation of the sympathetic PNS.

  13. Indian hedgehog roles in post-natal TMJ development and organization.

    PubMed

    Ochiai, T; Shibukawa, Y; Nagayama, M; Mundy, C; Yasuda, T; Okabe, T; Shimono, K; Kanyama, M; Hasegawa, H; Maeda, Y; Lanske, B; Pacifici, M; Koyama, E

    2010-04-01

    Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation. To determine whether it regulates those processes during post-natal life, we ablated Ihh in cartilage of neonatal mice and assessed the consequences on temporomandibular joint (TMJ) growth and organization over age. Ihh deficiency caused condylar disorganization and growth retardation and reduced polymorphic cell layer proliferation. Expression of Sox9, Runx2, and Osterix was low, as was that of collagen II, collagen I, and aggrecan, thus altering the fibrocartilaginous nature of the condyle. Though a disc formed, it exhibited morphological defects, partial fusion with the glenoid bone surface, reduced synovial cavity space, and, unexpectedly, higher lubricin expression. Analysis of the data shows, for the first time, that continuous Ihh action is required for completion of post-natal TMJ growth and organization. Lubricin overexpression in mutants may represent a compensatory response to sustain TMJ movement and function.

  14. Involvement of epithelial Wntless in the regulation of postnatal hair follicle morphogenesis.

    PubMed

    Huang, Sixia; Zhu, Xuming; Tao, Yixin; Sun, Qianqian; Wang, Lei; Li, Baojie; He, Lin; Guo, Xizhi; Ma, Gang

    2015-11-01

    The roles of the Wnt cargo receptor Wntless (Wls) during hair follicle (HF) induction and postnatal HF cycling in skin have been elucidated. However, whether Wls regulates postnatal HF morphogenesis remains unclear. In this study, we found that Wls is expressed in developing HF during the morphogenesis stage after birth. By knocking out Wls in mouse skin epithelia with hypomorphic K14-cre, we found that Wls is required for normal HF morphogenesis. Wls-deficient HFs prematurely regressed, which was possibly caused by abnormally activated TGF-β/JNK pathway. Although Wls was reported to be a direct target of the Wnt/β-catenin pathway, we found that epithelial β-catenin was not necessary to maintain Wls expression. Therefore, other signals are involved in regulating Wls transcription in mouse skin.

  15. 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.

  16. A systematic review of the effects of postnatal maternal anxiety on children

    PubMed Central

    Richardson, Gale A.; Fabio, Anthony

    2011-01-01

    Several decades of research have focused on the impact of exposure to postnatal depression on children, while anxiety has been largely overlooked. Estimates of the prevalence of postnatal maternal anxiety (PMA) range from 3% to 43%, suggesting PMA may be an important risk factor for adverse outcomes in children. This review summarizes what is known about the effects of PMA exposure on children and makes recommendations for future research. A systematic search of Ovid MEDLINE® and PsychINFO® through 2008 identified 18 studies that evaluated child outcomes associated with PMA exposure. Identified studies covered three domains: somatic, developmental, and psychological outcomes. The strongest evidence for an adverse effect of PMA exposure is in somatic and psychological outcomes; the evidence for an effect of PMA on child development is inconclusive. Methodological differences among the studies make comparisons difficult and there are a number of common limitations that challenge the validity of these studies. PMID:19789953

  17. Quantitative assessment of angiogenesis, perfused blood vessels and endothelial tip cells in the postnatal mouse brain.

    PubMed

    Wälchli, Thomas; Mateos, José María; Weinman, Oliver; Babic, Daniela; Regli, Luca; Hoerstrup, Simon P; Gerhardt, Holger; Schwab, Martin E; Vogel, Johannes

    2015-01-01

    During development and in various diseases of the CNS, new blood vessel formation starts with endothelial tip cell selection and vascular sprout migration, followed by the establishment of functional, perfused blood vessels. Here we describe a method that allows the assessment of these distinct angiogenic steps together with antibody-based protein detection in the postnatal mouse brain. Intravascular and perivascular markers such as Evans blue (EB), isolectin B4 (IB4) or laminin (LN) are used alongside simultaneous immunofluorescence on the same sections. By using confocal laser-scanning microscopy and stereological methods for analysis, detailed quantification of the 3D postnatal brain vasculature for perfused and nonperfused vessels (e.g., vascular volume fraction, vessel length and number, number of branch points and perfusion status of the newly formed vessels) and characterization of sprouting activity (e.g., endothelial tip cell density, filopodia number) can be obtained. The entire protocol, from mouse perfusion to vessel analysis, takes ∼10 d.

  18. 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.

  19. Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model

    PubMed Central

    Ono, Mitsuaki; Oshima, Masamitsu; Ogawa, Miho; Sonoyama, Wataru; Hara, Emilio Satoshi; Oida, Yasutaka; Shinkawa, Shigehiko; Nakajima, Ryu; Mine, Atsushi; Hayano, Satoru; Fukumoto, Satoshi; Kasugai, Shohei; Yamaguchi, Akira; Tsuji, Takashi; Kuboki, Takuo

    2017-01-01

    Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine. PMID:28300208

  20. Fate choice of post-natal mesoderm progenitors: skeletal versus cardiac muscle plasticity.

    PubMed

    Costamagna, Domiziana; Quattrocelli, Mattia; Duelen, Robin; Sahakyan, Vardine; Perini, Ilaria; Palazzolo, Giacomo; Sampaolesi, Maurilio

    2014-02-01

    Regenerative medicine for skeletal and cardiac muscles still constitutes a fascinating and ambitious frontier. In this perspective, understanding the possibilities of intrinsic cell plasticity, present in post-natal muscles, is vital to define and improve novel therapeutic strategies for acute and chronic diseases. In addition, many somatic stem cells are now crossing the boundaries of basic/translational research to enter the first clinical trials. However, it is still an open question whether a lineage switch between skeletal and cardiac adult myogenesis is possible. Therefore, this review focuses on resident somatic stem cells of post-natal skeletal and cardiac muscles and their plastic potential toward the two lineages. Furthermore, examples of myogenic lineage switch in adult stem cells are also reported and discussed.

  1. Generation of Murine Sympathoadrenergic Progenitor-Like Cells from Embryonic Stem Cells and Postnatal Adrenal Glands

    PubMed Central

    Saxena, Shobhit; Wahl, Joachim; Huber-Lang, Markus S.; Stadel, Dominic; Braubach, Peter; Debatin, Klaus-Michael; Beltinger, Christian

    2013-01-01

    Sympathoadrenergic progenitor cells (SAPs) of the peripheral nervous system (PNS) are important for normal development of the sympathetic PNS and for the genesis of neuroblastoma, the most common and often lethal extracranial solid tumor in childhood. However, it remains difficult to isolate sufficient numbers of SAPs for investigations. We therefore set out to improve generation of SAPs by using two complementary approaches, differentiation from murine embryonic stem cells (ESCs) and isolation from postnatal murine adrenal glands. We provide evidence that selecting for GD2 expression enriches for ESC-derived SAP-like cells and that proliferating SAP-like cells can be isolated from postnatal adrenal glands of mice. These advances may facilitate investigations about the development and malignant transformation of the sympathetic PNS. PMID:23675538

  2. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

    PubMed Central

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss; Wiese, Maria; Lundsager, Mia; Buschard, Karsten Stig; Hansen, Axel Kornerup; Frøkiær, Hanne

    2016-01-01

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND) 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice. PMID:26783537

  3. 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.

  4. 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.

  5. 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.

  6. Postnatal Persistent Infection with Classical Swine Fever Virus and Its Immunological Implications

    PubMed Central

    Rosell, Rosa; Pérez, Lester Josué; Frías-Leuporeau, Maria Teresa; Fraile, Lorenzo; Montoya, Maria; Cordoba, Lorena; Domingo, Mariano; Ehrensperger, Felix; Summerfield, Artur; Ganges, Llilianne

    2015-01-01

    It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed

  7. Postnatal neurodevelopmental expression and glutamate-dependent regulation of the ZNF804A rodent homologue.

    PubMed

    Chang, Eric H; Kirtley, Anne; Chandon, Toni-Shay S; Borger, Philip; Husain-Krautter, Sehba; Vingtdeux, Valerie; Malhotra, Anil K

    2015-10-01

    The zinc finger protein ZNF804A rs1344706 variant is a replicated genome-wide significant risk variant for schizophrenia and bipolar disorder. While its association with altered brain structure and cognition in patients and healthy risk allele carriers is well documented, the characteristics and function of the gene in the brain remains poorly understood. Here, we used in situ hybridization to determine mRNA expression levels of the ZNF804A rodent homologue, Zfp804a, across multiple postnatal neurodevelopmental time points in the rat brain. We found changes in Zfp804a expression in the rat hippocampus, frontal cortex, and thalamus across postnatal neurodevelopment. Zfp804a mRNA peaked at postnatal day (P) 21 in hippocampal CA1 and DG regions and was highest in the lower cortical layers of frontal cortex at P1, possibly highlighting a role in developmental migration. Using immunofluorescence, we found that Zfp804a mRNA and ZFP804A co-localized with neurons and not astrocytes. In primary cultured cortical neurons, we found that Zfp804a expression was significantly increased when neurons were exposed to glutamate [20μM], but this increase was blocked by the N-methyl-d-aspartate receptor (NMDAR) antagonist MK-801. Expression of Comt, Pde4b, and Drd2, genes previously shown to be regulated by ZNF804A overexpression, was also significantly changed in an NMDA-dependent manner. Our results describe, for the first time, the unique postnatal neurodevelopmental expression of Zfp804a in the rodent brain and demonstrate that glutamate potentially plays an important role in the regulation of this psychiatric susceptibility gene. These are critical steps toward understanding the biological function of ZNF804A in the mammalian brain.

  8. Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus.

    PubMed

    Tyzio, Roman; Minlebaev, Marat; Rheims, Sylvain; Ivanov, Anton; Jorquera, Isabelle; Holmes, Gregory L; Zilberter, Yuri; Ben-Ari, Yehezkiel; Khazipov, Rustem

    2008-05-01

    During postnatal development of the rat hippocampus, gamma-aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell-attached recordings of GABA(A) and N-methyl-D-aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride-extrusion and chloride-loading systems. Thus, the postnatal excitatory-to-inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings.

  9. 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.

  10. 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.

  11. Postnatal Support Strategies for Improving Rates of Exclusive Breastfeeding in Case of Caesarean Baby.

    PubMed

    Jesmin, E; Chowdhury, R B; Begum, S; Shapla, N R; Shahida, S M

    2015-10-01

    Despite awarness of the many advantages of breast feeding exclusive breastfeeding (EBF) rate is still lower than recommended practice and the rate is less in case of caesarean baby. In an effort towards achieving better breast feeding practices, UNICEF and WHO launched the baby friendly hospital initiative in 1991 to ensure that all maternity facilities support mothers in making the best choice about feeding. The implementation of effective programs improves rates of short and long term exclusive breast feeding even in case of caesarean baby. The objective of present study was to investigate whether postnatal support improves the rate of exclusive breast feeding in case of caesarean baby compared with usual hospital care. This was a longitudinal study over one and half year period, from April 2009 to October 2011 done in Combined Military Hospital in Mymensingh. A total of 565 pregnant women were included this study. Primary outcome was early establishment of breast feeding after caesarean section. Secondary outcome was exclusive breast feeding at discharge from hospital, two weeks and six weeks after caesarean section delivery. Early establishment of breast feeding within one hour after caesarean section was higher in postnatal support group than usual care group (70.29% vs. 57.14%). Rates of exclusive breastfeeding in the postnatal support strategies group were significantly higher when compared with those who received usual hospital care at discharge (89.13% vs. 75.94%, p=0.004), at 2 weeks (85.51% vs. 53.38%, p<0.001) and at 6 weeks (74.64% vs. 38.35%, p<0.001). Postnatal lactation support, as single intervention based in hospital significantly improves rates of exclusive breast feeding.

  12. 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.

  13. Variation in elemental intensities among teeth and between pre- and postnatal regions of enamel.

    PubMed

    Dolphin, Alexis E; Goodman, Alan H; Amarasiriwardena, Dulasiri D

    2005-12-01

    Microspatial analyses of the trace element composition of dental enamel are made possible using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Fine spatial resolution, multielement capabilities, and minimal sample destruction make this technique particularly well-suited for documenting the distribution of elements in sequentially calcifying layers of enamel. Because deciduous enamel forms from week 13 in utero up to 9 months postnatally (thereafter essentially becoming inert), the application of LA-ICP-MS allows for the retrospective measurement of prenatal and early postnatal trace-element uptake during a critical period of child development. In this study, we compared intra- and intertooth intensities of 25Mg, 57Fe, 66Zn, 68Zn, 88Sr, 138Ba, and 208Pb via LA-ICP-MS of 38 exfoliated deciduous incisors and canines donated by 36 participants in the Solís Valley Mexico Nutrition Collaborative Research Support Program (NCRSP). Pre- and postnatal comparisons within teeth showed significant increases (P < 0.001) and greater variation in the abundance of all isotopes in postnatal enamel, with the exception of a decrease in 25Mg (P < 0.001) and constant values for 88Sr (P = 0.681). Conversely, comparisons by tooth type and mouth quadrant revealed few significant differences between teeth of the same individual. We argue that more variation in the trace element composition of teeth occurs across developmental areas within a tooth than among different teeth of the same person. This study further demonstrates that sequentially calcifying areas of enamel have different chemical concentrations. The results support the use of microspatial analyses of enamel for understanding changes in nutrition, pollution, and residence.

  14. Postnatal persistent infection with classical Swine Fever virus and its immunological implications.

    PubMed

    Muñoz-González, Sara; Ruggli, Nicolas; Rosell, Rosa; Pérez, Lester Josué; Frías-Leuporeau, Maria Teresa; Fraile, Lorenzo; Montoya, Maria; Cordoba, Lorena; Domingo, Mariano; Ehrensperger, Felix; Summerfield, Artur; Ganges, Llilianne

    2015-01-01

    It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed

  15. Postnatal developmental expression of regulator of G protein signaling 14 (RGS14) in the mouse brain.

    PubMed

    Evans, Paul R; Lee, Sarah E; Smith, Yoland; Hepler, John R

    2014-01-01

    Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and mitogen-activated protein kinase (MAPK) signaling pathways. In the adult mouse brain, RGS14 mRNA and protein are found almost exclusively in hippocampal CA2 neurons. We have shown that RGS14 is a natural suppressor of CA2 synaptic plasticity and hippocampal-dependent learning and memory. However, the protein distribution and spatiotemporal expression patterns of RGS14 in mouse brain during postnatal development are unknown. Here, using a newly characterized monoclonal anti-RGS14 antibody, we demonstrate that RGS14 protein immunoreactivity is undetectable at birth (P0), with very low mRNA expression in the brain. However, RGS14 protein and mRNA are upregulated during early postnatal development, with protein first detected at P7, and both increasing over time until reaching highest sustained levels throughout adulthood. Our immunoperoxidase data demonstrate that RGS14 protein is expressed in regions outside of hippocampal CA2 during development including the primary olfactory areas, the anterior olfactory nucleus and piriform cortex, and the olfactory associated orbital and entorhinal cortices. RGS14 is also transiently expressed in neocortical layers II/III and V during postnatal development. Finally, we show that RGS14 protein is first detected in the hippocampus at P7, with strongest immunoreactivity in CA2 and fasciola cinerea and sporadic immunoreactivity in CA1; labeling intensity in hippocampus increases until adulthood. These results show that RGS14 mRNA and protein are upregulated throughout postnatal mouse development, and RGS14 protein exhibits a dynamic localization pattern that is enriched in hippocampus and primary olfactory cortex in the adult mouse brain.

  16. Interrelationships of Prenatal and Postnatal Growth, Hormones, Diet and Breast Cancer

    DTIC Science & Technology

    2001-06-01

    interrelationships, we hypothesized that insulin resistance will be positively associated with breast cancer. Further, we hypothesized that genetic susceptibility...and adolescent/adult diet and physical activity will modify the effect of insulin resistance on breast cancer. Specific aims were: (1) to undergo... insulin resistance -breast cancer relationship, and (3) to obtain fending to conduct a cohort study of the association between prenatal and postnatal

  17. Interrelationships of Prenatal and Postnatal Growth, Hormones, Diet, and Breast Cancer

    DTIC Science & Technology

    2003-06-01

    interrelationships, we hypothesized that insulin resistance will be positively associated with breast cancer. Further, we hypothesized that genetic susceptibility...and adolescent/adult diet and physical activity will modify the effect of insulin resistance on breast cancer. Specific aims were: 1) to undergo... insulin resistance -breast cancer relationship, and 3) to obtain finding to conduct a cohort study of the association between prenatal and postnatal growth

  18. Interrelationship of Prenatal and Postnatal Growth, Hormones, Diet and Breast Cancer

    DTIC Science & Technology

    2002-06-01

    interrelationships, we hypothesized that insulin resistance will be positively associated with breast cancer. Further, we hypothesized that genetic susceptibility...and adolescent/adult diet and physical activity will modify the effect of insulin resistance on breast cancer. Specific aims were: 1) to undergo... insulin resistance -breast cancer relationship, and 3) to obtain funding to conduct a cohort study of the association between prenatal and postnatal growth

  19. 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.

  20. Postnatal growth of the human pons: a morphometric and immunohistochemical analysis.

    PubMed

    Tate, Matthew C; Lindquist, Robert A; Nguyen, Thuhien; Sanai, Nader; Barkovich, A James; Huang, Eric J; Rowitch, David H; Alvarez-Buylla, Arturo

    2015-02-15

    Despite its critical importance to global brain function, the postnatal development of the human pons remains poorly understood. In the present study, we first performed magnetic resonance imaging (MRI)-based morphometric analyses of the postnatal human pons (0-18 years; n = 6-14/timepoint). Pons volume increased 6-fold from birth to 5 years, followed by continued slower growth throughout childhood. The observed growth was primarily due to expansion of the basis pontis. T2-based MRI analysis suggests that this growth is linked to increased myelination, and histological analysis of myelin basic protein in human postmortem specimens confirmed a dramatic increase in myelination during infancy. Analysis of cellular proliferation revealed many Ki67(+) cells during the first 7 months of life, particularly during the first month, where proliferation was increased in the basis relative to tegmentum. The majority of proliferative cells in the postnatal pons expressed the transcription factor Olig2, suggesting an oligodendrocyte lineage. The proportion of proliferating cells that were Olig2(+) was similar through the first 7 months of life and between basis and tegmentum. The number of Ki67(+) cells declined dramatically from birth to 7 months and further decreased by 3 years, with a small number of Ki67(+) cells observed throughout childhood. In addition, two populations of vimentin/nestin-expressing cells were identified: a dorsal group near the ventricular surface, which persists throughout childhood, and a parenchymal population that diminishes by 7 months and was not evident later in childhood. Together, our data reveal remarkable postnatal growth in the ventral pons, particularly during infancy when cells are most proliferative and myelination increases.

  1. 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.

  2. 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.

  3. Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

    PubMed

    Boullu-Ciocca, S; Tassistro, V; Dutour, A; Grino, M

    2015-12-01

    Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11β-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11β-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11β-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

  4. Substratum preferences of motor and sensory neurons in postnatal and adult rats.

    PubMed

    Gonzalez-Perez, Francisco; Alé, Albert; Santos, Daniel; Barwig, Christina; Freier, Thomas; Navarro, Xavier; Udina, Esther

    2016-02-01

    After peripheral nerve injuries, damaged axons can regenerate but functional recovery is limited by the specific reinnervation of targets. In this study we evaluated if motor and sensory neurites have a substrate preference for laminin and fibronectin in postnatal and adult stages. In postnatal dorsal root ganglia (DRG) explants, sensory neurons extended longer neurites on collagen matrices enriched with laminin (~50%) or fibronectin (~35%), whereas motoneurons extended longer neurites (~100%) in organotypic spinal cord slices embedded in fibronectin-enriched matrix. An increased percentage of parvalbumin-positive neurites (presumptive proprioceptive) vs. neurofilament-positive neurites was also found in DRG in fibronectin-enriched matrix. To test if the different preference of neurons for extracellular matrix components was maintained in vivo, these matrices were used to fill a chitosan guide to repair a 6-mm gap in the sciatic nerve of adult rats. However, the number of regenerating motor and sensory neurons after 1 month was similar between groups. Moreover, none of the retrotraced sensory neurons in DRG was positive for parvalbumin, suggesting that presumptive proprioceptive neurons had poor regenerative capabilities compared with other peripheral neurons. Using real-time PCR we evaluated the expression of α5β1 (receptor for fibronectin) and α7β1 integrin (receptor for laminin) in spinal cord and DRG 2 days after injury. Postnatal animals showed a higher increase of α5β1 integrin, whereas both integrins were similarly expressed in adult neurons. Therefore, we conclude that motor and sensory axons have a different substrate preference at early postnatal stages but this difference is lost in the adult.

  5. Developmental changes in the expression of ATP7A during a critical period in postnatal neurodevelopment.

    PubMed

    Niciu, M J; Ma, X-M; El Meskini, R; Ronnett, G V; Mains, R E; Eipper, B A

    2006-01-01

    ATP7A is a P-type ATPase that transports copper from cytosol into the secretory pathway for loading onto cuproproteins or efflux. Mutations in Atp7a cause Menkes disease, a copper-deficiency disorder fatal in the postnatal period due to severe neurodegeneration. Early postnatal copper injections are known to diminish degenerative changes in some human patients and mice bearing mutations in Atp7a. In situ hybridization studies previously demonstrated that ATP7A transcripts are expressed widely in the brain. ATP7A-specific antibody was used to study the neurodevelopmental expression and localization of ATP7A protein in the mouse brain. Based on immunoblot analyses, ATP7A expression is most abundant in the early postnatal period, reaching peak levels at P4 in neocortex and cerebellum. In the developing and adult brain, ATP7A levels are greatest in the choroid plexus/ependymal cells of the lateral and third ventricles. ATP7A expression decreases in most neuronal subpopulations from birth to adulthood. In contrast, ATP7A expression increases in CA2 hippocampal pyramidal and cerebellar Purkinje neurons. ATP7A is expressed in a subset of astrocytes, microglia, oligodendrocytes, tanycytes and endothelial cells. ATP7A is largely localized to the trans-Golgi network, adopting the cell-specific and developmentally-regulated morphology of this organelle. The presence of ATP7A in the axons of postnatal, but not adult, optic nerve suggests stage-specific roles for this enzyme. In sum, the precisely-regulated neurodevelopmental expression of ATP7A correlates well with the limited therapeutic window for effective treatment of Menkes disease.

  6. 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.

  7. 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

  8. 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.

  9. Alterations in central monoamine systems after postnatal lead acetate treatment in rats

    SciTech Connect

    Luthman, J. Univ. of Colorado Health Sciences Center, Denver, CO ); Lindqvist, E.; Olson, L. ); Gerhardt, G.A.; Hoffer, B.H. )

    1994-04-01

    The present study was undertaken to investigate the effect of postnatal lead exposure on central monoamine systems. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally for 20 days postnatally. Two groups of control rats received sodium acetate, or sodium acetate in oversized litters to compensate for lead-induced malnutrition in the high lead dose group, while nontreated animals also served as controls. At Day 21 or 51 regional tissue levels of monoamines were determined using HPLC techniques. No major changes were seen after the lead exposures in the levels of dopamine, noradrenaline, and serotonin, or metabolites of dopamine and serotonin, when compared to respective control groups. On the other hand, in the control group given sodium acetate in oversized litters some alterations of the monoamine levels were observed in frontal cortex and striatum at Day 21 compared to controls. At Day 51, the striatal homovanillic acid and 5-hydroxyindoleacetic acid levels were higher in the low lead dose group compared to those in the controls, No other changes in the monoamine levels were seen at Day 51. At 50-70 days postnatally, potassium-stimulated dopamine overflow was studied in striatum with in vivo chronoamperometry. In the high lead dose group the amplitudes of signals were lower in both the dorsal and ventral striatum compared to the controls, while no difference was seen in the clearance time of dopamine. The capacity of the dopamine terminals to respond to repeated stimulation was not affected by the lead exposure. Thus, the steady-state levels of monoamines were essentially unaltered after postnatal lead exposure in rats, while functional aspects of striatal dopamine transmission were affected after exposure to the higher dose of lead. These findings support the hypothesis that lead-induced changes in motor skills and exploratory behavior may be related to altered dopamine neurotransmission. 77 refs., 3 figs., 2 tabs.

  10. Prenatal and Postnatal Fruit and Vegetable Intake Among US Women: Associations with WIC Participation.

    PubMed

    Stallings, Tiffany L; Gazmararian, Julie A; Goodman, Michael; Kleinbaum, David

    2016-08-01

    Objective Evaluate variation in fruit and vegetable intake by Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participation and poverty status among pregnant, and postpartum women participating in the Infant Feeding Practice Study II (IFPSII). Methods IFPSII (2005-2007) followed US women from third trimester through 1 year postpartum through mailed questionnaires measuring income, WIC participation, breastfeeding; and dietary history questionnaires (DHQ) assessing prenatal/postnatal fruit and vegetable consumption. Poverty measurements used U.S. Census Bureau Federal Poverty thresholds to calculate percent of poverty index ratio (PIR) corresponding to WIC's financial eligibility (≤185 % PIR). Comparison groups: WIC recipients; WIC eligible (≤185 % PIR), but non-recipients; and women not financially WIC eligible (>185 % PIR). IFPSII participants who completed at least one DHQ were included. Intake variation among WIC/poverty groups was assessed by Kruskal-Wallis tests and between groups by Mann-Whitney Wilcoxon tests and logistic regression. Mann-Whitney Wilcoxon tests examined postnatal intake by breastfeeding. Results Prenatal vegetable intake significantly varied by WIC/poverty groups (p = 0.04) with WIC recipients reporting significantly higher intake than women not financially WIC eligible (p = 0.02); association remained significant adjusting for confounders [odds ratio 0.66 (95 % confidence interval: 0.49-0.90)]. Prenatal fruit and postnatal consumption did not significantly differ by WIC/poverty groups. Postnatal intake was significantly higher among breastfeeding than non-breastfeeding women (fruit: p < 0.0001; vegetable: p = 0.006). Conclusions for Practice Most intakes did not significantly differ by WIC/poverty groups and thus prompts research on WIC recipient's dietary behaviors, reasons for non-participation in WIC, and the influence of the recent changes to the WIC food package.

  11. Exploratory behavior in rats postnatally exposed to cocaine and housed in an enriched environment.

    PubMed

    Magalhães, Ana; Melo, Pedro; Alves, Cecília Juliana; Tavares, Maria Amélia; de Sousa, Liliana; Summavielle, Teresa

    2008-10-01

    Exposure to cocaine in early periods of postnatal life is usually associated with changes in development of neurotransmitter systems and structure of the central nervous system. Such changes are most likely correlated with behavioral alterations. Environmental enrichment conditions (EC) in early stages is a factor that affects structural and behavioral development. The purpose of this study is to examine the effects of EC on rats postnatally exposed to cocaine on exploratory behavior. Wistar rats were assigned to four groups-Group 1: pups exposed to cocaine hydrochloride (15 mg/kg body weight/day) s.c., in two daily doses, from postnatal day (PND) 1 to 28 and reared in EC; Group 2: pups exposed to cocaine as previously described and reared in a standard environmental conditions (SC); Group 3: pups saline-injected and reared in EC; and Group 4: pups saline-injected and reared in SC. On PND 21, 24, and 28, groups of four rats (to reduce anxiety) were placed for 10 minutes into an arena with several objects. The following exploratory behavioral categories were examined: object interaction, exploration, manipulation, approximation, and total time of object contact. Animals from Group 2 showed decreased object interaction and total contact on PND 21. Control offspring reared in EE showed decreases in exploratory behavior at all ages analyzed compared with the control SE group, while cocaine-exposed animals reared in EC showed decreased object interaction, object approximation, and total exploratory behavior. The results in this group suggest that EC improved information acquisition and memory processes in animals postnatally exposed to cocaine.

  12. 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.

  13. 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.

  14. Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.

    PubMed

    Cuomo, V; Cagiano, R; Mocchetti, I; Coen, E; Cattabeni, F; Racagni, G

    1983-01-01

    Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.

  15. Metabolic perturbations of postnatal growth restriction and hyperoxia-induced pulmonary hypertension in a bronchopulmonary dysplasia model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Neonatal pulmonary hypertension (PH) is a common manifestation of bronchopulmonary dysplasia (BPD) and contributes to increased morbidity and mortality of preterm birth. Postnatal growth restriction and hyperoxia are independent contributors to PH development, as indicated by our previ...

  16. Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.

    PubMed

    Al Jaam, Bilal; Heu, Katy; Pennarubia, Florian; Segelle, Alexandre; Magnol, Laetitia; Germot, Agnès; Legardinier, Sébastien; Blanquet, Véronique; Maftah, Abderrahman

    2016-09-01

    Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1(cax/cax) (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1(cax/cax) mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1(cax/cax) SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7(+)/MYOD(-) progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice.

  17. 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.

  18. Postnatal caffeine treatment affects differently two pentylenetetrazol seizure models in rats.

    PubMed

    Tchekalarova, Jana; Kubová, Hana; Mares, Pavel

    2009-09-01

    Effects of repeated postnatal administration of caffeine (10 and 20mg/kg s.c. daily from P7 to P11) were studied in two models of epileptic seizures characterized by spike-and-wave EEG rhythm in 18- and 25-day-old rats. Rhythmic metrazol activity (RMA, model of human absences) was induced by low dose of pentylenetetrazol (PTZ, 20mg/kg or 40mg/kg, i.p.) and minimal clonic seizures (model of human myoclonic seizures) by two successive doses of PTZ (20 and 40mg/kg i.p.). Early postnatal caffeine treatment resulted in significant changes of RMA only in 18-day-old rats. Anticonvulsant effects were observed in RMA episodes elicited by the 20-mg/kg dose of PTZ in both caffeine groups whereas latency of RMA episodes induced by the 40-mg/kg dose was shortened and their duration was prolonged. No changes were found in 25-day-old animals. Incidence, EEG and motor pattern of minimal clonic seizures were not changed. Some animals in both control age groups exhibited transition to generalized tonic-clonic seizures. This type of seizures never appeared in caffeine-treated 25-day-old animals. Mixed effects of postnatal caffeine exposure were demonstrated; these predominantly anticonvulsant effects are age- and model-specific.

  19. Influence of Gestational Age and Postnatal Age on Speech Sound Processing in NICU infants

    PubMed Central

    Key, Alexandra P.F.; Lambert, E. Warren; Aschner, Judy L.; Maitre, Nathalie L.

    2012-01-01

    The study examined the effect of gestational (GA) and postnatal (PNA) age on speech sound perception in infants. Auditory ERPs were recorded in response to speech sounds (CV syllables) in 50 infant NICU patients (born at 24–40 weeks gestation) prior to discharge. Efficiency of speech perception was quantified as absolute difference in mean amplitudes of ERPs in response to vowel (/a/–/u/) and consonant (/b/–/g/, /d/–/g/) contrasts within 150–250, 250–400, 400–700 ms after stimulus onset. Results indicated that both GA and PNA affected speech sound processing. These effects were more pronounced for consonant than vowel contrasts. Increasing PNA was associated with greater sound discrimination in infants born at or after 30 weeks GA, while minimal PNA-related changes were observed for infants with GA less than 30 weeks. Our findings suggest that a certain level of brain maturity at birth is necessary to benefit from postnatal experience in the first 4 months of life, and both gestational and postnatal ages need to be considered when evaluating infant brain responses. PMID:22332725

  20. 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.

  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. Antenatal and Postnatal Psychopathology Among Women with Current and Past Eating Disorders: Longitudinal Patterns

    PubMed Central

    Easter, Abigail; Solmi, Francessca; Bye, Amanda; Taborelli, Emma; Corfield, Freya; Schmidt, Ulrike; Treasure, Janet; Micali, Nadia

    2015-01-01

    This study aims to investigate longitudinal patterns of psychopathology during the antenatal and postnatal periods among women with current (C-ED) and past (P-ED) eating disorders. Women were recruited to a prospective longitudinal study: C-ED (n = 31), P-ED (n = 29) and healthy control (HC; n = 57). Anxiety, depression and ED symptoms were measured at four time points: first/second trimester, third trimester, 8 weeks and 6 months postpartum. Linear mixed effects models were used to test for group differences. Women with C-ED and P-ED, in all diagnostic categories, had significantly higher levels of psychopathology at all time points. ED symptoms decreased in the C-ED group, compared with an overall increase in the other two groups but subsequently increased after pregnancy. Overall, depression and state and trait anxiety scores decreased in the C-ED group compared with the HC group throughout the antenatal and postnatal periods. High levels of psychopathology are common throughout the antenatal and postnatal periods among women with current and past ED, and despite some overall reductions, symptoms remain clinically significant. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd. PMID:25345371

  3. 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.

  4. Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice

    PubMed Central

    Al Jaam, Bilal; Heu, Katy; Pennarubia, Florian; Segelle, Alexandre; Magnol, Laetitia; Germot, Agnès; Blanquet, Véronique; Maftah, Abderrahman

    2016-01-01

    Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1cax/cax (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1cax/cax mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1cax/cax SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7+/MYOD− progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice. PMID:27628322

  5. Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep.

    PubMed

    Veiga-Lopez, Almudena; Moeller, Jacob; Sreedharan, Rohit; Singer, Kanakadurga; Lumeng, Carey; Ye, Wen; Pease, Anthony; Padmanabhan, Vasantha

    2016-02-01

    Among potential contributors for the increased incidence of metabolic diseases is the developmental exposure to endocrine-disrupting chemicals such as bisphenol A (BPA). BPA is an estrogenic chemical used in a variety of consumer products. Evidence points to interactions of BPA with the prevailing environment. The aim of this study was to assess the effects of prenatal exposure to BPA on postnatal metabolic outcomes, including insulin resistance, adipose tissue distribution, adipocyte morphometry, and expression of inflammatory markers in adipose tissue as well as to assess whether postnatal overfeeding would exacerbate these effects. Findings indicate that prenatal BPA exposure leads to insulin resistance in adulthood in the first breeder cohort (study 1), but not in the second cohort (study 2), which is suggestive of potential differences in genetic susceptibility. BPA exposure induced adipocyte hypertrophy in the visceral fat depot without an accompanying increase in visceral fat mass or increased CD68, a marker of macrophage infiltration, in the subcutaneous fat depot. Cohens effect size analysis found the ratio of visceral to subcutaneous fat depot in the prenatal BPA-treated overfed group to be higher compared with the control-overfed group. Altogether, these results suggest that exposure to BPA during fetal life at levels found in humans can program metabolic outcomes that lead to insulin resistance, a forerunner of type 2 diabetes, with postnatal obesity failing to manifest any interaction with prenatal BPA relative to insulin resistance and adipocyte hypertrophy.

  6. 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.

  7. Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep

    PubMed Central

    Veiga-Lopez, Almudena; Moeller, Jacob; Sreedharan, Rohit; Singer, Kanakadurga; Ye, Wen; Pease, Anthony

    2015-01-01

    Among potential contributors for the increased incidence of metabolic diseases is the developmental exposure to endocrine-disrupting chemicals such as bisphenol A (BPA). BPA is an estrogenic chemical used in a variety of consumer products. Evidence points to interactions of BPA with the prevailing environment. The aim of this study was to assess the effects of prenatal exposure to BPA on postnatal metabolic outcomes, including insulin resistance, adipose tissue distribution, adipocyte morphometry, and expression of inflammatory markers in adipose tissue as well as to assess whether postnatal overfeeding would exacerbate these effects. Findings indicate that prenatal BPA exposure leads to insulin resistance in adulthood in the first breeder cohort (study 1), but not in the second cohort (study 2), which is suggestive of potential differences in genetic susceptibility. BPA exposure induced adipocyte hypertrophy in the visceral fat depot without an accompanying increase in visceral fat mass or increased CD68, a marker of macrophage infiltration, in the subcutaneous fat depot. Cohens effect size analysis found the ratio of visceral to subcutanous fat depot in the prenatal BPA-treated overfed group to be higher compared with the control-overfed group. Altogether, these results suggest that exposure to BPA during fetal life at levels found in humans can program metabolic outcomes that lead to insulin resistance, a forerunner of type 2 diabetes, with postnatal obesity failing to manifest any interaction with prenatal BPA relative to insulin resistance and adipocyte hypertrophy. PMID:26646100

  8. β-defensins and the epididymis: contrasting influences of prenatal, postnatal, and adult scenarios

    PubMed Central

    Ribeiro, Camilla M; Silva, Erick JR; Hinton, Barry T; Avellar, Maria Christina W

    2016-01-01

    β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant expression of a variety of β-defensins in the postnatal epididymis of different species. A gradient of region- and cell-specific expression of these proteins is observed in the epithelium of the postnatal epididymis. Their secretion into the luminal fluid and binding to spermatozoa as they travel along the epididymis has suggested their involvement in reproduction-specific tasks. Therefore, continuous attention has been given to various β-defensins for their role in sperm function and fertility. Although β-defensins are largely dependent on androgens, the underlying mechanisms regulating their expression and function in the epididymis are not well understood. Recent investigation has pointed out to a new and interesting scenario where β-defensins emerge with a different expression pattern in the Wolffian duct, the embryonic precursor of the epididymis, as opposed to the adult epididymis, thereby redefining the concept concerning the multifunctional roles of β-defensins in the developing epididymis. In this review, we summarize some current views of β-defensins in the epididymis highlighting our most recent data and speculations on their role in the developing epididymis during the prenatal-to-postnatal transition, bringing attention to the many unanswered questions in this research area that may contribute to a better understanding of epididymal biology and male fertility. PMID:26763543

  9. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

    PubMed

    Muñoz-González, Sara; Perez-Simó, Marta; Muñoz, Marta; Bohorquez, José Alejandro; Rosell, Rosa; Summerfield, Artur; Domingo, Mariano; Ruggli, Nicolas; Ganges, Llilianne

    2015-07-09

    Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

  10. Postnatal hypoglycaemia and gluconeogenesis in the newborn rat. Delayed onset of gluconeogenesis in prematurely delivered newborns.

    PubMed Central

    Fernández, E; Valcarce, C; Cuezva, J M; Medina, J M

    1983-01-01

    The concentrations of glucose and lactate in the blood and of liver glycogen, and the phosphoenolpyruvate carboxykinase activity in liver and kidney of term and preterm newborn rats, were studied during the first 6 h post partum. Rates of lactate turnover and gluconeogenesis in vivo from [U-14C]lactate at 3 h and 6 h post partum were also quantified. The development of the prolonged postnatal hypoglycaemia observed after birth in the premature newborn rat is associated with lower rates of glucose production through glycogenolysis and gluconeogenesis; liver glycogenolysis was the main contributing factor to the glucose available during the neonatal period studied in both groups. Delayed induction of liver phosphoenolpyruvate carboxykinase activity was observed in premature newborn rats. Renal phosphoenolpyruvate carboxykinase activity increased 72% from birth in preterm newborns, but only a 25% increase was found in term newborns during the same experimental period. The gluconeogenesis in vivo from [U-14C]lactate paralleled the appearance of cytosolic phosphoenolpyruvate carboxykinase activity in the liver of both groups of newborns. Blood lactate concentrations remained higher in preterm than in term newborns. The postnatal utilization of lactate via the gluconeogenic pathway in either group of newborns was always less than 20% of the total lactate used. The results presented are discussed in relation to the development of postnatal hypoglycaemia and gluconeogenesis in the premature newborn rat. PMID:6615479

  11. 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

  12. 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.

  13. Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

    PubMed Central

    Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy; Sontag, Ryan L.; Weitz, Karl K.; Shukla, Anil K.; Nguyen, Son N.; Kim, Young-Mo; Zink, Erika M.; Luders, Teresa; Frevert, Charles W.; Gharib, Sina A.; Laskin, Julia; Carson, James P.; Metz, Thomas O.; Corley, Richard A.; Ansong, Charles

    2017-01-01

    Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylphosphatidylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murine lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6–8 week mice (adult) identified 924 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. This multi-omic view provides a unique resource and deeper insight into normal pulmonary development. PMID:28145528

  14. Antenatal and postnatal psychopathology among women with current and past eating disorders: longitudinal patterns.

    PubMed

    Easter, Abigail; Solmi, Francessca; Bye, Amanda; Taborelli, Emma; Corfield, Freya; Schmidt, Ulrike; Treasure, Janet; Micali, Nadia

    2015-01-01

    This study aims to investigate longitudinal patterns of psychopathology during the antenatal and postnatal periods among women with current (C-ED) and past (P-ED) eating disorders. Women were recruited to a prospective longitudinal study: C-ED (n = 31), P-ED (n = 29) and healthy control (HC; n = 57). Anxiety, depression and ED symptoms were measured at four time points: first/second trimester, third trimester, 8 weeks and 6 months postpartum. Linear mixed effects models were used to test for group differences. Women with C-ED and P-ED, in all diagnostic categories, had significantly higher levels of psychopathology at all time points. ED symptoms decreased in the C-ED group, compared with an overall increase in the other two groups but subsequently increased after pregnancy. Overall, depression and state and trait anxiety scores decreased in the C-ED group compared with the HC group throughout the antenatal and postnatal periods. High levels of psychopathology are common throughout the antenatal and postnatal periods among women with current and past ED, and despite some overall reductions, symptoms remain clinically significant. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

  15. 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.

  16. Inactivation of β-catenin results in the reduction of postnatal body weight gain.

    PubMed

    Wang, Hong-Tao; Zeng, Lin; Zhang, Xin; Li, Kui; Zu, Yong; Liu, Ji-wei; Liu, Yong-jie; Zhu, Zhi-chuan; Xiong, Zhi-Qi; Zheng, Jing; Hu, Ze-Lan

    2014-01-01

    Arcuate nucleus of hypothalamus (ARH) is the core component in the regulation circuits of food intake and energy homeostasis. ARH projections to other parts of the hypothalamus and to extrahypothalamic areas are established in the postnatal two weeks, which is a pivotal stage for individual development. β-Catenin, a cell adhesion protein and also the mediator of canonical Wnt signaling pathway, plays an important role in embryonic development and adult homeostasis. However, whether β-catenin plays any roles in the development of hypothalamus is not clear. Here, we report that perinatal conditional knockout of β-catenin by CamKIIα-Cre in forebrain reduces body weight gain from P8 and dramatically shortens life span. Quantitative PCR and in situ hybridization results showed the expression of NPY mRNA in the ARH of β-catenin CKO mice at P15 is obviously increased compared with that of littermate controls, whereas the expression of POMC mRNA is significantly decreased, which suggested the reduction of postnatal body weight gain might be due to the deficiency of food intake. Together, β-catenin might play an important role in the regulation of food intake and postnatal body weight gain probably through affecting the development of ARH circuits.

  17. Postnatal change in sulcal length asymmetry in cerebrum of cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Sakamoto, Kazuhito; Sawada, Kazuhiko; Fukunishi, Katsuhiro; Noritaka, Imai; Sakata-Haga, Hiromi; Yoshihiro, Fukui

    2014-02-01

    The purpose of this study was to determine the timing of the onset of adult-type sulcal length asymmetry during postnatal development of the male cynomolgus monkey cerebrum. The monkey brain has already reached adult size by 3 months of age, although the body weight only represents 1/8 of the adult body weight by that time. The fronto-occipital length and the cerebral width also reached adult levels by that postnatal age with no left/right bias. Consistently, lengths of the major primary sulci reached adult levels by 3 months of age, and then decreased slightly in sexually mature monkeys (4-6.5 years of age). Asymmetry quotient analysis showed that sulcal length asymmetry patterns gradually changed during postnatal development. The male adult pattern of sulcal length asymmetry was acquired after 24 months of age. In particular, age-dependent rightward lateralization of the arcuate sulcal length was revealed during cerebral maturation by three-way ANOVA. The results suggest that the regional difference in cerebral maturation from adolescence to young adulthood modifies the sulcal morphology with characteristic asymmetric patterns in male cynomolgus monkeys.

  18. 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.

  19. The endocannabinoid-CB(1) receptor system in pre- and postnatal life.

    PubMed

    Fride, Ester

    2004-10-01

    Recent research suggests that the endogenous cannabinoids ("endocannabinoids") and their cannabinoid receptors have a major influence during pre- and postnatal development. First, high levels of the endocannaboid anandamide and cannabinoid receptors are present in the preimplantation embryo and in the uterus, while a temporary reduction of anandamide levels is essential for embryonal implantation. In women accordingly, an inverse association has been reported between fatty acid amide hydrolase (the anandamide degrading enzyme) in human lymphocytes and miscarriage. Second, CB(1) receptors display a transient presence in white matter areas of the pre- and postnatal nervous system, suggesting a role for CB(1) receptors in brain development. Third, endocannabinoids have been detected in maternal milk and activation of CB(1) receptors appears to be critical for milk sucking by newborn mice, apparently activating oral-motor musculature. Fourth, anandamide has neuroprotectant properties in the developing postnatal brain. Finally, prenatal exposure to the active constituent of marihuana (Delta(9)-tetrahydrocannabinol) or to anandamide affects prefrontal cortical functions, memory and motor and addictive behaviors, suggesting a role for the endocannabinoid CB(1) receptor system in the brain structures which control these functions. Further observations suggest that children may be less prone to psychoactive side effects of Delta(9)-tetrahydrocannabinol or endocannabinoids than adults. The medical implications of these novel developments are far reaching and suggest a promising future for cannabinoids in pediatric medicine for conditions including "non-organic failure-to-thrive" and cystic fibrosis.

  20. Adolescent Experience Affects Postnatal Ultrasonic Vocalizations and Gene Expression in Future Offspring

    PubMed Central

    Bodi, Caroline M.; Vassoler, Fair M.; Byrnes, Elizabeth M.

    2017-01-01

    The present study measured postnatal ultrasonic vocalization (USV) and gene expression to examine potential changes in communication and/or attachment in the offspring of mothers exposed to morphine during adolescence. Offspring of morphine-exposed (Mor-F1), saline-exposed (Sal-F1), or non-handled control (Con-F1) female Sprague–Dawley rats were tested for separation-induced distress calls and maternal potentiation of distress calls during early postnatal development. We also examined relative expression of dopamine D2 receptor and mu opioid receptor (oprm1) mRNA in the nucleus accumbens and hypothalamus in these offspring, as their activity has been implicated in the regulation of postnatal USV in response to maternal separation. The findings indicate that adolescent experiences of future mothers, including their 10 daily saline or morphine injections, can result in significant region-specific differences in gene expression. In addition, these experiences resulted in fewer numbers of separation-induced distress calls produced by offspring. In contrast, augmented maternal potentiation was only observed in Mor-F1 offspring. PMID:26999300

  1. Pre- and Postnatal Exposure to Low Dose Glufosinate Ammonium Induces Autism-Like Phenotypes in Mice

    PubMed Central

    Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

    2014-01-01

    Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 – two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods. PMID:25477793

  2. 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

  3. 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.

  4. Postnatal treatment of rats with adrenergic receptor agonists or antagonists influences differentiation of sexual behavior.

    PubMed

    Jarzab, B; Sickmöller, P M; Geerlings, H; Döhler, K D

    1987-12-01

    The aim of the study was to investigate the possible role of the adrenergic system in development and differentiation of neural centers controlling sexual behavior in adulthood. For this purpose normal and androgenized female rats were treated with the alpha 1-receptor antagonist prazosin, the alpha 2-receptor agonist clonidine, or the alpha 2-receptor antagonist yohimbine-HCl throughout the first week of life. In adulthood all animals were ovariectomized and, after appropriate hormone-priming, they were tested for the capacity to display female and male sexual behavior patterns. Alteration of adrenergic transmission during the critical postnatal period for sexual differentiation of neural centers resulted in significant changes in the capacity to express female lordosis behavior in adulthood. In nonandrogenized animals clonidine significantly reduced the capacity for lordosis behavior. In androgenized animals clonidine had the opposite effect; it attenuated the inhibitory effect of testosterone propionate (TP) on differentiation of lordosis behavior. Prazosin, which was without effect in nonandrogenized animals, also attenuated the inhibitory effect of TP on differentiation of lordosis behavior. Yohimbine was without effect in androgenized and nonandrogenized animals. There was no influence of any of the adrenergic drugs on differentiation of male sexual behavior. In conclusion, differentiation of lordosis behavior seems to be mediated or modulated via adrenergic transmission. The defeminizing effect of testosterone postnatally on the differentiation of lordosis behavior seems to be expressed via alpha 1-adrenergic transmission, and diminished adrenergic activity during the postnatal period seems to protect the developing brain against this effect of testosterone.

  5. 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

  6. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

    PubMed Central

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  7. 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.

  8. Autosomal Recessive Hypophosphatasia Manifesting in Utero with Long Bone Deformity but Showing Spontaneous Postnatal Improvement

    PubMed Central

    Stevenson, David A.; Carey, John C.; Coburn, Stephen P.; Ericson, Karen L.; Byrne, Janice L. B.; Mumm, Steven; Whyte, Michael P.

    2008-01-01

    Context: Hypophosphatasia (HPP) is a heritable metabolic disorder of the skeleton that includes variable expressivity conditioned by gene dosage effect and the variety of mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene. Patient age when skeletal problems first manifest generally predicts the clinical course, with perinatal HPP causing bone disease in utero with postnatal lethality. Objective: Our objective was to identify TNSALP mutations and characterize the inheritance pattern of a family with clinically variable HPP with one child manifesting in utero with long bone deformity but showing spontaneous prenatal and postnatal improvement. Design: TNSALP enzyme and substrate analysis and TNSALP mutation analysis were performed on all family members. Patients: A boy with HPP showing long bone deformity that spontaneously improved in utero and after birth is described. His older brother has the childhood form of HPP without findings until after infancy. His parents and twin sister are clinically unaffected. Results: Both boys are compound heterozygotes for the same missense mutations in TNSALP, documenting autosomal recessive inheritance for their HPP. The parents each carry one defective allele. Conclusions: The patient is an autosomal recessive case of HPP with prenatal long bone deformity but with spontaneous prenatal and postnatal improvement. Thus, prenatal detection by sonography of bowing of long bones from HPP, even with autosomal recessive inheritance, does not necessarily predict lethality but can represent variable expressivity or the effects of modifiers on the TNSALP defect(s). PMID:18559907

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. The postnatal maturation of efferent tubules in the rat: a light and electron microscopy study.

    PubMed

    Francavilla, S; Moscardelli, S; Bruno, B; Barcellona, P S; De Martino, C

    1986-07-01

    The postnatal maturation of the epithelium and tubule wall of efferent tubules in the rat was investigated by light and transmission electron microscopy, from birth to 50 days of age, when sperms were released from the seminiferous tubules and appeared in the genital duct. At the end of the first week of life, an endocytotic apparatus is differentiated in the epithelial cells. During the third week of life, efferent tubules developed specializations for the transport of sperms and fluids, namely the appearance of ciliated elements interspersed among the principal cells of the epithelium, and differentiation of myoid elements in the tubule wall. The appearance of specializations related to endocytosis and fluid transport across the epithelium preceded the canalization of the seminiferous cords which, in fact, is reported to appear at the end of the second week of life in the rat, along with the initial secretion of testicular fluid. This suggested that the maturation of efferent tubules is not triggered by the passage of testicular fluid, as surmised for the postnatal differentiation of caput epididymis. The postnatal maturation of efferent tubules was almost complete 35 days after birth. The appearance of sperms in the genital duct of 50-day-old animals was not associated with any remarkable structural change.

  14. Postnatal expression of myosin isoforms in an expiratory muscle--external abdominal oblique.

    PubMed

    Watchko, J F; Daood, M J; Vazquez, R L; Brozanski, B S; LaFramboise, W A; Guthrie, R D; Sieck, G C

    1992-11-01

    We studied the postnatal expression of heavy-chain (MHC) and native myosin isoforms in an expiratory abdominal muscle of the rat, the external abdominal oblique (EO). Moreover, we contrasted EO myosin expression with that of the costal diaphragm (DIA) to draw inspiratory vs. expiratory muscle comparisons during development. Examination of MHC gels demonstrated a mature phenotype of slow and adult fast myosin isoforms at an earlier age in the EO (day 60) than in the DIA [day > 115 (adult)]. The mature MHC phenotype of the EO was characterized by a preponderance of MHC 2B, whereas the DIA was characterized by approximately equal portions of MHC slow, MHC 2A, and MHC 2X. During early postnatal development, there was a delay in the expression of MHC 2A in the EO compared with the DIA. However, MHC 2B, expressed later in development in both muscles, was noted in the EO before the DIA. We conclude that 1) the EO mature myosin phenotype is characterized by a preponderance of fast myosin isoforms and 2) the EO and DIA muscles are subject to different temporal patterns of isoform expression during postnatal development.

  15. Postnatal expression of myosin isoforms in the genioglossus and diaphragm muscles.

    PubMed

    Brozanski, B S; Daood, M J; Watchko, J F; LaFramboise, W A; Guthrie, R D

    1993-04-01

    We studied the expression of myosin heavy chain (MHC) and native myosin isoforms in the genioglossus (GG) and costal diaphragm (DIA) muscles of the rat during postnatal development using both denaturing and nondenaturing gel electrophoresis. Primary myotubes in both fast and slow muscles homogeneously express slow as well as embryonic myosin. Since the adult GG is comprised primarily of fast MHC isoforms, whereas the adult DIA is characterized by a mixture of MHC slow and fast isoforms, we hypothesized that the GG and DIA would be subject to different temporal patterns of MHC isoform expression during postnatal development. Native myosin and MHC gels demonstrated a persistence of neonatal MHC (MHC neo) on day 25 in the GG, whereas this isoform was not detected beyond day 21 in the DIA. The MHC phenotype in GG of the adult demonstrated a predominance of MHC 2X (35% +/- 8) and MHC 2B (45% +/- 10) with a smaller proportion of MHC 2A (19% +/- 5). In contrast, the MHC phenotype in adult DIA was characterized by approximately equal proportions of MHC slow (25% +/- 3), MHC 2A (34% +/- 10), and MHC 2X (31% +/- 12) with a small percentage of MHC 2B (9% +/- 7). These data suggest that postnatal regulation of MHC expression in the GG and DIA is muscle specific.

  16. The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells

    PubMed Central

    Liu, Siyuan John; Nowakowski, Tomasz Jan; Hong, Sung Jun; Gertz, Caitlyn; Salinas, Ryan D.; Zarabi, Hosniya; Kriegstein, Arnold R.; Lim, Daniel A.

    2015-01-01

    Summary While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations. PMID:25800779

  17. Pre- and Post-Natal Maternal Depressive Symptoms in Relation with Infant Frontal Function, Connectivity, and Behaviors

    PubMed Central

    Soe, Ni Ni; Wen, Daniel J.; Poh, Joann S.; Li, Yue; Broekman, Birit F. P.; Chen, Helen; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D.; Meaney, Michael J.; Rifkin-Graboi, Anne; Qiu, Anqi

    2016-01-01

    This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children’s externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls. PMID:27073881

  18. Pre- and Post-Natal Maternal Depressive Symptoms in Relation with Infant Frontal Function, Connectivity, and Behaviors.

    PubMed

    Soe, Ni Ni; Wen, Daniel J; Poh, Joann S; Li, Yue; Broekman, Birit F P; Chen, Helen; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Meaney, Michael J; Rifkin-Graboi, Anne; Qiu, Anqi

    2016-01-01

    This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children's externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls.

  19. Promoting Retention

    PubMed Central

    Hall, LaToya N.; Ficker, Lisa J.; Chadiha, Letha A.; Green, Carmen R.; Jackson, James S.; Lichtenberg, Peter A.

    2016-01-01

    Objectives: The objectives of this study were to evaluate the capability of a research volunteer registry to retain community-dwelling African American older adults, and to explore demographic and health factors associated with retention. Method: A logistic regression model was used to determine the influence of demographics, health factors, and registry logic model activities on retention in a sample of 1,730 older African American adults. Results: Almost 80% of participants active in the volunteer research registry between January 2012 and June 2015 were retained. Employment, being referred to research studies, a higher number of medical conditions, and more follow-up contacts were associated with an increased likelihood of retention. Older age, more months in the registry, and more mobility problems decreased the likelihood of retention. Discussion: These results suggest the Michigan Center for Urban African American Aging Research logic model promotes retention through involving older African American adults in research through study referrals and intensive follow-up. The loss of participants due to age- and mobility-related issues indicate the registry may be losing its most vulnerable participants. PMID:28138501

  20. Expression of Slug in S100β-protein-positive cells of postnatal developing rat anterior pituitary gland.

    PubMed

    Horiguchi, Kotaro; Fujiwara, Ken; Tsukada, Takehiro; Yako, Hideji; Tateno, Kozue; Hasegawa, Rumi; Takigami, Shu; Ohsako, Shunji; Yashiro, Takashi; Kato, Takako; Kato, Yukio

    2016-02-01

    Among heterogeneous S100β-protein-positive (S100β-positive) cells, star-like cells with extended cytoplasmic processes, the so-called folliculo-stellate cells, envelop hormone-producing cells or interconnect homophilically in the anterior pituitary. S100β-positive cells are known, from immunohistochemistry, to emerge from postnatal day (P) 10 and to proliferate and migrate in the pare