EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000
István M. Ábrahám
Abstract Postnatal handling, as a crucial early life experience, plays an essential role in the development of hypothalamo-pituitary,adrenal axis responses to stress. The impact of postnatal handling on the reactivity of stress-related neuronal circuitries was investigated in animals that were handled for the first 21 days of life and as adults they were exposed to physical (ether) or emotional (restraint) challenge. To assess neuronal activation we relied on the induction of immediate-early gene product c-Fos and analysed its spatial and temporal distribution at various time intervals after stress. Ether and restraint commonly activated parvocellular neurons in the hypothalamic paraventricular nucleus, and resulted in activation of brain areas providing stress-related information to the hypothalamic effector neurons and/or in regions governing autonomic and behavioural responses to stress. Beyond these areas, the strength and timing of c-Fos induction showed stressor specificity in olfactory and septal region, basal ganglia, hypothalamus, hippocampal formation, amygdala and brainstem. Handled rats displayed a lower number of c-Fos-positive cell nuclei and weaker staining intensity than non-handled controls in the hypothalamic paraventricular nucleus, bed nucleus of stria terminalis, central nucleus of amygdala, hippocampus, piriform cortex and posterior division of the cingulum. Significant differences were revealed in timing of c-Fos induction as a function of stressor and early life experience. Together, these data provide functional anatomical evidence that environmental enrichment in the early postnatal period attenuates the reactivity of stress-related neuronal circuitries in the adult rat brain. [source]

Postnatal handling reverses social anxiety in serotonin receptor 1A knockout mice

GENES, BRAIN AND BEHAVIOR, Issue 1 2010
C. Zanettini
Mice lacking the serotonin receptor 1A (Htr1a knockout, Htr1aKO) show increased innate and conditioned anxiety. This phenotype depends on functional receptor activity during the third through fifth weeks of life and thus appears to be the result of long-term changes in brain function as a consequence of an early deficit in serotonin signaling. To evaluate whether this phenotype can be influenced by early environmental factors, we subjected Htr1a knockout mice to postnatal handling, a procedure known to reduce anxiety-like behavior and stress responses in adulthood. Offspring of heterozygous Htr1a knockout mice were separated from their mother and exposed 15 min each day from postnatal day 1 (PD1) to PD14 to clean bedding. Control animals were left undisturbed. Maternal behavior was observed during the first 13 days of life. Adult male offspring were tested in the open field, social approach and resident,intruder tests and assessed for corticosterone response to restraint stress. Knockout mice showed increased anxiety in the open field and in the social approach test as well as an enhanced corticosterone response to stress. However, while no effect of postnatal handling was seen in wild-type mice, handling reduced anxiety-like behavior in the social interaction test and the corticosterone response to stress in knockout mice. These findings extend the anxiety phenotype of Htr1aKO mice to include social anxiety and demonstrate that this phenotype can be moderated by early environmental factors. [source]

Developmental Changes of Seminiferous Tubule in Prenatal, Postnatal and Adult Testis of Bonnet Monkey (Macaca radiata)

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2008
S. Prakash
Summary This paper is a part of our study on the male reproductive system of bonnet monkey. The developmental changes in testis of bonnet monkey were studied qualitatively and quantitatively, at the light microscopy level. Testicular development appears to primarily involve tubular growth that starts immediately after birth. There is a gradual increase in the number of tubules in the prenatal to neonatal stage in testis, without an increase in the volume. Increase in the number of tubules in the neonatal testis was achieved by an increase in the length of the tubules and reduction in the interstitial proportion. Scattered spermatogonial cells in the tubules of neonatal testis indicate the rapid growth rate of the tubules. Increase in tubular length along with diameter seems to be a continuous process until puberty. This is the first report on the developmental changes in the testis during fetal, postnatal and adult stages in the bonnet monkey. [source]

Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants

ACTA PAEDIATRICA, Issue 10 2003
R Tadokoro
Aim: To examined the changes in basal plasma concentrations of glicentin in developing children and the postnatal and postprandial changes in plasma glicentin levels in infants. Methods: Glicentin, an active component of enteroglucagon, is considered to have a significant trophic action on the intestinal mucosa. Fasting plasma concentrations of glicentin in healthy children and in term and preterm infants were measured before and 30 min after feeding during the first 14 d of life. Results: Plasma basal concentrations of glicentin in children under 1 y of age were significantly higher than those in children aged 1 to 15 y. Plasma basal concentrations of glicentin at 5 or 6 d (2496 and 2190 pg/ml) and at 14 d (2987 and 2817 pg/ml) after birth were significantly higher than those at 1 or 2 d (1098 and 1240 pg/ml) after birth in normal birthweight (NBW) and low-birthweight (LBW) infants. There was no significant difference in the glicentin level between infants at 1 or 2 d (1864 pg/ml) and at 5 or 6 d (1910 pg/ml) after birth in very-low birthweight (VLBW) infants, but the levels at 14 d (3310 pg/ml) after birth were significantly higher than either of those levels. Plasma glicentin concentrations after feeding were significantly higher than those before feeding at 1 or 2 d and at 5 or 6 d after birth in NBW and LBW infants, but a significant increase in the plasma glicentin level after feeding was first observed at 14 d after birth in VLBW infants. There were no significant differences in the basal plasma (2401 and 2718 pg/ml) and postprandial (3007 and 3912 pg/ml) glicentin levels between breastfed and formula-fed infants. Conclusion: The results of the study suggest that glicentin may play an important role in intestinal mucosal growth in the early period of life, although its role in VLBW infants should be further investigated. [source]

Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool

DEVELOPMENTAL DYNAMICS, Issue 7 2008
Nina Solberg
Abstract Canonical Wnt signaling is crucial for the correct development of both cortical and hippocampal structures in the dorsal telencephalon. In this study, we examined the role of the canonical Wnt signaling in the dorsal telencephalon of mouse embryos at defined time periods by inhibition of the pathway with ectopic expression of Dkk1. Transgenic mice with the D6-driven Dkk1 gene exhibited reduced canonical Wnt signaling in the cortex and hippocampus. As a result, all hippocampal fields were reduced in size. Neurogenesis in the dentate gyrus was severely reduced both in the premigratory and migratory progenitor pool. The lower number of progenitors in the dentate gyrus was not rescued after migration to the subgranular zone and thus the dentate gyrus lacked the entire internal blade and a part of the external blade from postnatal to adult stages. Developmental Dynamics 237:1799,1811, 2008. © 2008 Wiley-Liss, Inc. [source]

Chronological gene expression of ADAMs during testicular development: Prespermatogonia (gonocytes) express fertilin , (ADAM2)

DEVELOPMENTAL DYNAMICS, Issue 3 2003
Carolina Rosselot
Abstract Immediately after birth, primordial germinal cell-derived prespermatogonia (PSG), located in the center of the testicular cords, migrate between adjacent Sertoli cells to establish contact with the cord basal lamina. PSG migration suggests continued assembly and disassembly of cell,cell contacts by a molecular mechanism that may involve integrins and their ligands, the disintegrin domain of spermatogenic cell-specific plasma membrane proteins called ADAMs. We have analyzed the temporal gene expression of selected ADAMs in intact fetal, early postnatal, and pubertal rat testis and Sertoli,spermatogenic cell cocultures by reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunocytochemistry. We report that several ADAM transcripts are expressed in fetal, neonatal, and prepubertal testes. Cyritestin (ADAM3), ADAM5, ADAM6, and ADAM15 are expressed in day 17 fetal testes. In contrast, no expression of fertilin , (ADAM1) and fertilin , (ADAM 2) was detected in fetal testes. Fertilin , gene expression starts after postnatal day 2, subsequent to the expression of fertilin ,, which occurs on postnatal day 1. After postnatal day 2, all the indicated ADAMs, including the fertilin , and fertilin ,, continue to be expressed. Transcripts of spermatogenic cell-specific fertilin ,, fertilin ,, ADAM3, and ADAM5 were detected during the coculture of PSG with Sertoli cells for up to 72 hr after plating. The presence of fertilin , mRNA and protein in cocultured PSG was visualized by in situ hybridization and immunocytochemistry, respectively. These observations indicate that PSG in coculture with Sertoli cells provide a suitable approach for analyzing cell,cell adhesive responses involving spermatogenic cell-specific ADAMs. Development Dynamics 458,467, 2003. © 2003 Wiley-Liss, Inc. [source]

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

DEVELOPMENTAL NEUROBIOLOGY, Issue 11 2009
Mônica Marins
Abstract 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 ,M) 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. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source]

Distribution of neurotrophin-3 during the ontogeny and regeneration of the lizard (Gallotia galloti) visual system

DEVELOPMENTAL NEUROBIOLOGY, Issue 1 2008
E. Santos
Abstract We have previously described the spontaneous regeneration of retinal ganglion cell axons after optic nerve (ON) transection in the adult Gallotia galloti. As neurotrophin-3 (NT-3) is involved in neuronal differentiation, survival and synaptic plasticity, we performed a comparative immunohistochemical study of NT-3 during the ontogeny and regeneration (after 0.5, 1, 3, 6, 9, and 12 months postlesion) of the lizard visual system to reveal its distribution and changes during these events. For characterization of NT-3+ cells, we performed double labelings using the neuronal markers HuC-D, Pax6 and parvalbumin (Parv), the microglial marker tomato lectin or Lycopersicon esculentum agglutinin (LEA), and the astroglial markers vimentin (Vim) and glial fibrillary acidic protein (GFAP). Subpopulations of retinal and tectal neurons were NT-3+ from early embryonic stages to adulthood. Nerve fibers within the retinal nerve fiber layer, both plexiform layers and the retinorecipient layers in the optic tectum (OT) were also stained. In addition, NT-3+/GFAP+ and NT-3+/Vim+ astrocytes were detected in the ON, chiasm and optic tract in postnatal and adult lizards. At 1 month postlesion, abundant NT-3+/GFAP+ astrocytes and NT-3,/LEA+ microglia/macrophages were stained in the lesioned ON, whereas NT-3 became downregulated in the experimental retina and OT. Interestingly, at 9 and 12 months postlesion, the staining in the experimental retina resembled that in control animals, whereas bundles of putative regrown fibers showed a disorganized staining pattern in the OT. Altogether, we demonstrate that NT-3 is widely distributed in the lizard visual system and its changes after ON transection might be permissive for the successful axonal regrowth. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source]

Maternally separated rats show deficits in maternal care in adulthood

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2001
Vedran Lovic
Abstract Although there is considerable research on the phenomenology, neuroendocrinology, neuroanatomy, and sensory control of maternal behavior, little is known about the influences of early postnatal and postweaning experiences on the development of maternal behavior. The purpose of this study was to assess how early life separation from the mother rat affects development of the offspring's juvenile and adult maternal behavior. From postnatal Days 1 to 17, 3 female rats within each litter were separated (SEP) from the mother and the rest of the litter for 5 hr daily while 3 of their sisters were not maternally separated (NSEP). On postnatal Day 21, all subjects were weaned and randomly assigned to one of three juvenile conditions. One female from both SEP and NSEP groups was either isolated (I), given a social conspecific (S), or given 1- to 4-day-old pups (P) for 5 consecutive days. Maternal behavior of SEP and NSEP animals was assessed and recorded on each of the 5 days. Once all animals reached adulthood, they were mated, gave birth, and were assessed for their maternal behavior. We found that the effects of maternal separation on juvenile maternal-like behaviors were minimal. On the other hand, maternal separation reduced adult maternal licking and crouching over pups. In addition, there was a significant interaction between postnatal and juvenile experience on maternal crouching in maternal animals. These results are discussed in terms of the variety of possible behavioral, endocrine, and neurochemical mechanisms that mediate the effects of early life experiences on adult maternal behavior. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 19,33, 2001 [source]

Recruiting new neurons from the subventricular zone to the rat postnatal cortex: an organotypic slice culture model

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2008
A. G. Dayer
Abstract The neurogenic subventricular zone (SVZ) of the lateral ventricle is a potential source for neuronal replacement in the postnatal or adult neocortex after injury. Here we present a novel model system to directly explore the cellular mechanisms of this process. In order to visualize directed migration from the SVZ towards the cortex, we transplanted green fluorescent protein-labeled progenitor/stem cells into the SVZ of newborn rats. At 2 days after transplantation, we generated organotypic slice cultures and applied fluorescent time-lapse imaging to explore directly the migration and integration of donor cells into the host tissue for up to 2 weeks. Our studies revealed that subventricular grafts provide a significant number of immature neurons to neocortical regions. In the cortex, immature neurons first migrate radially towards the pial surface and then differentiate into GABAergic interneurons. We conclude that our model system presents a novel and effective experimental paradigm to evaluate the recruitment of SVZ-derived neurons into the postnatal cortex, a phenomenon that may represent a potential route for cortical repair. [source]

Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2003
Hong Li
Abstract NB-2, a member of the contactin subgroup in the immunoglobulin superfamily, is expressed specifically in the postnatal nervous system, reaching a maximum level at 3 weeks postnatal. NB-2 displays neurite outgrowth-promoting activity in vitro. To assess its function in the nervous system, we generated mutant mice in which a part of the NB-2 gene was ablated and replaced with the tau-LacZ gene. The general appearance of NB-2-deficient mice and their gross anatomical features were normal. The LacZ expression patterns in heterozygous mice revealed that NB-2 is preferentially expressed in the central auditory pathways. In the audiogenic seizure test, NB-2-deficient mice exhibited a lower incidence of wild running, but a higher mortality rate than the wild-type littermates. c-Fos immunohistochemistry demonstrated that neural excitability induced by the audiogenic seizure test in the NB-2-deficient mice was prominently attenuated in both the dorsal and external cortices of the inferior colliculus, where enhanced neural excitability was observed in the wild-type mice. In response to pure-tone stimulation after priming, NB-2-deficient mice exhibited a diffuse and low level of c-Fos expression in the central nucleus of the inferior colliculus, which was distinctly different from the band-like c-Fos expression corresponding to the tonotopic map in the wild-type littermates. Taken together, these results suggest that a lack of NB-2 causes impairment of the neuronal activity in the auditory system. [source]

Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003
Manel M. Santafé
Abstract We studied the presynaptic muscarinic autoreceptor subtypes controlling ACh release and their relationship with voltage-dependent calcium channels in the neuromuscular synapses of the Levator auris longus muscle from adult (30,40 days) and newborn (3,6 and 15 days postnatal) rats. Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potentials. In some experiments we previously incubated the muscle with calcium channel blockers (nitrendipine, ,-conotoxin-GVIA and ,-Agatoxin-IVA) before determining the muscarinic response. In the adult, the M1 receptor-selective antagonist pirenzepine (10 µm) reduced evoked neurotransmission (, 47%). The M2 receptor-selective antagonist methoctramine (1 µm) increased the evoked release (, 67%). Both M1- and M2-mediated mechanisms depend on calcium influx via P/Q-type synaptic channels. We found nothing to indicate the presence of M3 (4-DAMP-sensitive) or M4 (tropicamide-sensitive) receptors in the muscles of adult or newborn rats. In the 3,6-day newborn rats, pirenzepine reduced the evoked release (, 30%) by a mechanism independent of L-, N- and P/Q-type calcium channels, and the M2 antagonist methoctramine (1 µm) unexpectedly decreased the evoked release (, 40%). This methoctramine effect was a P/Q-type calcium-channel-dependent mechanism. However, upon maturation in the first two postnatal weeks, the M2 pathway shifted to perform the calcium-dependent release-inhibitory activity found in the adult. We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse. [source]

Postnatal innervation of the rat superior colliculus by axons of late-born retinal ganglion cells

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2002
Elizabeth J. Dallimore
Abstract Rat retinal ganglion cells (RGCs) are generated between embryonic day (E) 13 and E19. Retinal axons first reach the superior colliculus at E16/16.5 but the time of arrival of axons from late-born RGCs is unknown. This study examined (i) whether there is a correlation between RGC genesis and the timing of retinotectal innervation and (ii) when axons of late-born RGCs reach the superior colliculus. Pregnant Wistar rats were injected intraperitoneally with bromodeoxyuridine (BrdU) on E16, E18 or E19. Pups from these litters received unilateral superior colliculus injections of fluorogold (FG) at ages between postnatal (P) day P0 and P6, and were perfused 1,2 days later. RGCs in 3 rats from each BrdU litter were labelled in adulthood by placing FG onto transected optic nerve. Retinas were cryosectioned and the number of FG, BrdU and double-labelled (FG+/BrdU+) RGCs quantified. In the E16 group, the proportion of FG-labelled RGCs that were BrdU+ did not vary with age, indicating that axons from these cells had reached the superior colliculus by P0/P1. In contrast, for the smaller cohorts of RGCs born on E18 or E19, the proportion of BrdU+ cells that were FG+ increased significantly after birth; axons from most RGCs born on E19 were not retrogradely FG-labelled until P4/P5. Thus there is a correlation between birthdate and innervation in rat retinotectal pathways. Furthermore, compared to the earliest born RGCs, axons from late-born RGCs take about three times longer to reach the superior colliculus. Later-arriving axons presumably encounter comparatively different growth terrains en route and eventually innervate more differentiated target structures. [source]

Postnatal handling alters the activation of stress-related neuronal circuitries

Effects of supra-physiological changes in human ovarian hormone levels on maximum force production of the first dorsal interosseus muscle

EXPERIMENTAL PHYSIOLOGY, Issue 2 2005
Kirsty Jayne Elliott
The purpose of this study was to investigate the effects of supra-physiological changes in ovarian hormone levels on maximum force production in two conditions, one physiological (pregnancy) and one pseudo-physiological (in vitro fertilization (IVF) treatment). Forty IVF patients were tested at four distinct stages of treatment and 35 women were tested during each trimester of pregnancy and following parturition. Maximum voluntary isometric force per unit cross-sectional area of the first dorsal interosseus muscle was measured. Plasma concentrations of total and bioavailable oestradiol and testosterone were measured, in addition to the total concentrations of progesterone and human chorionic gonadotropin. Despite significant changes in the concentrations of total progesterone, 17,-oestradiol, bioavailable oestradiol and testosterone between phases, strength did not change significantly throughout IVF treatment (1.30 ± 0.29, 1.16 ± 0.38, 1.20 ± 0.29 and 1.26 ± 0.34 N mm,2, respectively, in the 4 phases of IVF treatment). Force production was significantly higher during the second trimester of pregnancy than following childbirth (1.33 ± 0.20 N mm,2 at week 12 of pregnancy, 1.51 ± 0.42 N mm,2 at week 20, 1.15 ± 0.26 N mm,2 at week 36 and 0.94 ± 0.31 N mm,2 at week 6 postnatal) but was not significantly correlated with any of the hormones measured. These data suggest that extreme changes in the concentrations of reproductive hormones do not affect the maximum force-generating capacity of young women. [source]

Postnatal handling reverses social anxiety in serotonin receptor 1A knockout mice

Handling and environmental enrichment do not rescue learning and memory impairments in ,CamKIIT286A mutant mice

GENES, BRAIN AND BEHAVIOR, Issue 3 2003
A. C. Need
Environmental enrichment and postnatal handling have been shown to improve learning and memory in the Morris water maze, and to rescue impairments caused by genetic modification, age or genetic background. Mice with a targeted point mutation that prevents autophosphorylation at threonine-286 of the ,-isoform of the Ca2+/calmodulin-dependent kinase II have impaired hippocampus-dependent and -independent strategy learning and memory in the water maze. We have investigated whether these impairments can be rescued with a combination of postnatal handling and environmental enrichment in a hybrid genetic background. Severe impairments were seen in acquisition and probe trials in both enriched and nonenriched mutants, indicating that enrichment did not rescue the learning and memory impairments. However, enrichment did rescue a specific performance deficit; enhanced floating behaviour, in the mutants. In summary, we have shown the lack of autophosphorylation of the ,-isoform of the Ca2+/calmodulin-dependent kinase II prevents enrichment-induced rescues of strategy learning and memory impairments. Furthermore, we have established that there are enrichment mechanisms that are independent of this autophosphorylation. [source]

Temporal control of gene recombination in astrocytes by transgenic expression of the tamoxifen-inducible DNA recombinase variant CreERT2

GLIA, Issue 1 2006
Petra G. Hirrlinger
Abstract Inducible gene modification using the Cre/loxP system provides a valuable tool for the analysis of gene function in the active animal. GFAP-Cre transgenic mice have been developed to achieve gene recombination in astrocytes, the most abundant cells of the central nervous system, with pivotal roles during brain function and pathology. Unfortunately, these mice displayed neuronal recombination as well, since the GFAP promoter is also active in embryonic radial glia, which possess a substantial neurogenic potential. To enable the temporal control of gene deletions in astrocytes only, we generated a transgenic mouse with expression of CreERT2, a fusion protein of the DNA recombinase Cre and a mutated ligand-binding domain of the estrogen receptor, under the control of the human GFAP promoter. In offspring originating from crossbreedings of GFAP-CreERT2-transgenic mice with various Cre-sensitive reporter mice, consecutive intraperitoneal injections of tamoxifen induced genomic recombination selectively in astrocytes of almost all brain regions. In Bergmann glia, which represent the main astroglial cell population of the cerebellum, virtually all cells showed successful gene recombination. When adult mice received cortical stab wound lesions, simultaneously given tamoxifen induced substantial recombination in reactive glia adjacent to the site of injury. These transgenic GFAP-CreERT2 mice will allow the functional analysis of loxP-modified genes in astroglia of the postnatal and adult brain. © 2006 Wiley-Liss, Inc. [source]

Postnatal neurogenesis in the dentate gyrus of the guinea pig

HIPPOCAMPUS, Issue 3 2005
Sandra Guidi
Abstract In all species examined, the dentate gyrus develops over an extended period that begins during gestation and continues up to adulthood. The aim of this study was to investigate the pattern of postnatal cell production in the dentate gyrus of the guinea pig, a rodent whose brain development has features more closely resembling the human condition than the most commonly used rodents (rat and mouse). Animals of different postnatal (P) ages received one or multiple injections of bromodeoxyuridine (BrdU), and the number of labeled cells in the dentate gyrus was counted after time intervals of 24 h or longer. The total granule cell number and the volume of the granule cell layer were evaluated in Nissl-stained brain sections from P1 and P30 animals. P1,P5 animals were treated with MK-801 to analyze the effect of NMDA receptor blockade on cell proliferation. Cell production occurred at a high rate (9,000,13,000 labeled cells 24 h after one injection) from P1 to P20, with a peak at 3,6 days of age, and then slowly declined from P20 to P30. The production of new cells continued in adult animals, although at a much-reduced rate (400 cells 24 h after one injection). About 20% of the labeled cells survived after a 17-day period and most (60%) of these cells had a neuronal phenotype. The total number of granule cells increased over the first postnatal month; in 30-day-old animals, it was 20% greater than in 1-day-old animals. Administration of MK-801 to P1,P5 animals caused an increase in cell proliferation restricted to the dorsal dentate gyrus. The present data show that, although the guinea pig dentate gyrus develops largely before birth, the production of new neurons continues at a high rate during the first postnatal month, leading to a considerable increase in cell number. This developmental pattern, resembling the human and nonhuman primate condition, may make the guinea pig a useful rodent model in developmental studies on dentate gyrus neurogenesis. © 2004 Wiley-Liss, Inc. [source]

Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1,

HUMAN MUTATION, Issue 2 2009
Wenke Seifert
Abstract Cohen syndrome is characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in COH1 (VPS13B) have been found in patients with Cohen syndrome from diverse ethnic origins. We have carried out mutation analysis in twelve novel patients with Cohen syndrome from nine families. In this series, we have identified 13 different mutations in COH1, twelve of these are novel including six frameshift mutations, four nonsense mutations, two splice site mutations, and a one-codon deletion. Since different transcripts of COH1 have been reported previously, we have analysed the expression patterns of COH1 splice variants. The transcript variant NM_152564 including exon 28b showed ubiquitous expression in all examined human tissues. In contrast, human brain and retina showed differential splicing of exon 28 (NM_017890). Moreover, analysis of mouse tissues revealed ubiquitous expression of Coh1 homologous to human NM_152564 in all examined tissues but no prevalent alternative splicing. © 2008 Wiley-Liss, Inc. [source]

Epigenetic regulation and downstream targets of the Rhox5 homeobox gene

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2008
S. Shanker
Summary The discovery of the Rhox homeobox gene cluster on the X chromosome opens up new vistas in the regulation of reproductive processes in mammals. In mice, this cluster comprises more than 30 genes that are selectively expressed in reproductive tissues. A subset of Rhox genes are androgen and AR regulated in postnatal and adult Sertoli cells, making them candidates to mediate androgen-dependent steps during spermatogenesis. The best characterized of these androgen/AR-regulated genes is Rhox5 (Pem), the founding member of the Rhox gene cluster. Targeted deletion of Rhox5 in mice causes male subfertility marked by increased germ-cell apoptosis and decreased sperm count and motility. Microarray analyses identified a wide variety of genes regulated by Rhox5 in Sertoli cells. One of them is the tumour suppressor UNC5C, a pro-apoptotic molecule previously only known to be involved in brain development. Targeted deletion of Unc5c causes decreased germ-cell apoptosis in postnatal and adult testes, indicating that it also has a role in spermatogenesis and supporting a model in which Rhox5 promotes germ-cell survival by downregulating Unc5c. Rhox5 has two independently regulated promoters that have distinct expression patterns. The unique tissue-specific and developmentally regulated transcription pattern of these two promoters appear to be controlled by DNA methylation. Both promoters are methylated in tissues in which they are not expressed, suggesting that DNA methylation serves to repress Rhox5 expression in inappropriate cell types and tissues. In summary, the Rhox gene cluster is an epigenetically regulated set of genes encoding a large number of transcription factors that are strong candidates to regulate gametogenesis and other aspects of reproduction. [source]

Climate and population density induce long-term cohort variation in a northern ungulate

JOURNAL OF ANIMAL ECOLOGY, Issue 5 2001
Mads C. Forchhammer
Summary 1,Density-dependent and climatic conditions experienced by individuals before and after birth differ considerably between cohorts. Such early environmental variability has the potential to create persistent fitness differences among cohorts. Here we test the hypothesis that conditions experienced by individuals in their early development will have long-term effects on their life history traits. 2,We approached this by analysing and contrasting the effects of climate (the North Atlantic Oscillation, NAO) and population density at year of birth on cohort birth weight, birth date, litter size, age of maturity, survival and fecundity of Soay sheep, Ovies aries L., ewes in the population on the island of Hirta, St Kilda, Scotland. 3,Significant intercohort variations were found in life history traits. Cohorts born after warm, wet and windy (high NAO) winters were lighter at birth, born earlier, less likely to have a twin and matured later than cohorts born following cold and dry (low NAO) winters. High population densities in the winter preceding birth also had a negative effect on birth weight, birth date and litter size, whereas high postnatal densities delayed age of first reproduction. 4,High NAO winters preceding birth depressed juvenile survival but increased adult survival and fecundity. The negative influence of high NAO winters on juvenile survival is likely to be related to mothers' compromised physical condition while the cohort is in utero, whereas the positive influence on adult survival and fecundity may relate to the improved postnatal forage conditions following high NAO winters. High pre- and postnatal population densities decreased juvenile (neonatal, yearling) and adult (2,4 years) survivorship but had no significant effect fecundity. [source]

Ontogeny of human hepatic cytochromes P450

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2007
Ronald N. Hines
Abstract Significant changes in drug-metabolizing enzyme (DME) expression occur during ontogeny. Such changes can have a profound effect on therapeutic efficacy in the fetus and child, as well as the risk for adverse drug reactions. To gain a better understanding of DME ontogeny, enzyme contents for six key cytochromes P450 were measured in 240 human liver samples representing ages from 8 weeks gestation to 18 years. Where possible, both quantitative western blotting and activity assays with probe substrates were performed. Although oversimplified, the DME can be grouped into one of three categories. As typified by CYP3A7, some enzymes are expressed at their highest level during the first trimester and either remain at high concentrations or decrease during gestation and are silenced or expressed at low levels within 1,2 years after birth. These data cause one to query whether these enzymes have an important endogenous function. Representatives of a second group, CYP3A5 and CYP2C19, are expressed at relatively constant levels throughout gestation. Postnatal increases in CYP2C19 are observed within the first year, but not for CYP3A5. CYP2C9, 2E1, and 3A4 are more typical of a third group of enzymes that are not expressed or are expressed at low levels in the fetus with the onset of expression generally in either the second or third trimester. Substantial increases in expression are observed within the first 1,2 years after birth; however, considerable interindividual variability is observed in the immediate postnatal (1,6 months) onset or increase in expression of these enzymes, often resulting in a window of hypervariability. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:169,175, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20179 [source]

Opioidergic regulation of astroglial/neuronal proliferation: where are we now?

JOURNAL OF NEUROCHEMISTRY, Issue 4 2008
Tim J. Sargeant
Abstract Opiate drugs, such as codeine, morphine, and heroin, are powerful analgesics, but also are used as drugs of abuse because of their psychogenic properties. Many studies have shown that opiates impact on cellular proliferation in the adult and developing brain, although anatomical pathologies are lacking in in utero exposed infants and opioid knockout mice. Recent research has defined a context-dependent role for the opioid system in neurogenesis in the adult hippocampus with exercise. Opioids have been shown to interact with proliferating cells of the postnatal subventricular zone of the lateral ventricles. The subventricular zone is also a region of adult neurogenesis, a fact that was not well established at the time this earlier research was conducted. Although a relationship between opioids and fetal neurogenesis has yet to be firmly established, many studies have implicated the opioid system in this process. One common factor that links neurogenesis in adult, postnatal, and fetal structures is the involvement of neuronal progenitor cells of the astrocytic lineage. It is therefore of interest that opioids have been consistently shown to impact upon astrocytic proliferation. It is the intention of this paper to review the literature that has established a role for the opioid system in neurogenesis in vivo in fetal, postnatal, and adult animals and to examine the links of opioids to modulation of astrocytic proliferation. [source]

Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomas

JOURNAL OF NEUROCHEMISTRY, Issue 4 2002
Rolf Mentlein
Abstract Pleiotrophin (PTN) is a mitogenic/angiogenic, 15.3 kDa heparin-binding peptide that is found in embryonic or early postnatal, but rarely in adult, tissues. Since developmentally regulated factors often re-appear in malignant cells, we examined PTN expression in human glioma cell lines, cell cultures derived from solid gliomas and glioma sections. PTN mRNA or protein was detected by reverse transcriptase-polymerase chain reaction, immunohistochemistry, western blot or enzyme-linked immunoassay in all WHO III and IV grade gliomas and cells analyzed in vitro or in situ. One WHO II grade glioma investigated was PTN negative. In vitro, PTN was synthesized in perinuclear regions of glioma cells, secreted into the cultivation medium, but its production varied considerably between glioma cells cultivated from different solid gliomas or glioma cell lines. In situ, PTN expression was restricted to distinct parts/cells of the tumour. PTN did not influence the proliferation of glioma cells themselves, but stimulated [3H]thymidine incorporation into DNA of microglial cells. Furthermore, in Boyden chamber assays, PTN showed a strong chemotactic effect on murine BV-2 microglial cells. PTN is supposed to be a paracrine growth/angiogenic factor that is produced by gliomas and contributes to their malignancy by targeting endothelial and microglial cells. [source]

Long-Term Modulation By Postnatal Oxytocin of the ,2 -Adrenoceptor Agonist Binding Sites in Central Autonomic Regions and the Role of Prenatal Stress

JOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2004
Z. Díaz-Cabiale
Abstract The aim of this work was to evaluate whether oxytocin administered in male rats subcutaneously early in life in the absence or presence of food restriction during pregnancy has life-long effects on the ,2 -agonist binding sites in the nucleus of the solitarii tract (NTS), in the hypothalamus and the amygdala, as evaluated by quantitative receptor autoradiography. Maternal food restriction alone increased the affinity of the ,2 -agonist [3H]UK14.304 binding sites exclusively in the NTS. In offspring from ad libitum fed dams, oxytocin treatment significantly increased the density of ,2 -agonist binding sites in the NTS and in the hypothalamus. The Kd value of the ,2 -agonist binding sites in the hypothalamus of these rats, but not in the other regions studied, was also significantly increased. In offspring from food-restricted dams, oxytocin treatment produced a significant increase of the Bmax values in the hypothalamus and the amygdala and the Kd value of the ,2 -agonist binding sites in the NTS of these rats also was selectively and significantly increased. These results suggest that a postnatal, oxytocin-induced increase of regional ,2 -adrenoceptor function can be seen in adulthood by a persistent, regionally selective increase in the density of central ,2 -adrenoceptor agonist binding sites, in the absence of an affinity change in the NTS. Such a regional increase of ,2 -adrenoceptor signalling in adulthood may contribute to the anti-stress action of postnatal oxytocin. By contrast, after prenatal stress, the potential increase in ,2 -adrenoceptor signalling takes place via selective increases of density with no changes of affinity of the ,2 -agonist binding sites in the hypothalamus and the amygdala. [source]

The Interaction of Gestational and Postnatal Ethanol Experience on the Adolescent and Adult Odor-Mediated Responses to Ethanol in Observer and Demonstrator Rats

ALCOHOLISM, Issue 10 2010
Amber M. Eade
Background:, Gestational ethanol exposure enhances the adolescent reflexive sniffing response to ethanol odor. Postnatal exposures of naïve animals as either an observer (i.e., conspecific) or demonstrator (i.e., intoxicated peer) using a social transmission of food odor preference paradigm also yields enhanced odor-mediated responses. Studies on the interaction of fetal and postnatal exposures using the social transmission paradigm have been limited to the responses of observers. When combined, the enhanced response is greater than either form of exposure alone and, in observer females, yields adult persistence. The absence of a male effect is noteworthy, given that chemosensory mechanisms are suggested to be an important antecedent factor in the progression of ethanol preference. Observers gain odor information on the breath of the demonstrator through social interaction. Demonstrators experience the pharmacologic properties of ethanol along with retronasal and hematogenic olfaction. Thus, we tested whether augmentation of the fetal ethanol-induced behavioral response with postnatal exposure as a demonstrator differed from that as an observer. We also examined whether re-exposure as a demonstrator yields persistence in both sexes. Methods:, Pregnant dams were fed an ethanol containing or control liquid diet throughout gestation. Progeny received four ethanol or water exposures: one every 48 hours through either intragastric infusion or social interaction with the infused peer beginning on P29. The reflexive behavioral sniffing response to ethanol odor was tested at postnatal (P) day 37 or P90, using whole-body plethysmography. Results:, When tested in either adolescence or adulthood - fetal ethanol exposed adolescent ethanol observers and demonstrators significantly differed in their odor-mediated response to ethanol odor both between themselves and from their respective water controls. Nonetheless, adolescent ethanol re-exposure as a demonstrator, like an observer, enhanced the reflexive sniffing response to ethanol odor at both testing ages by augmenting the known effects of prior fetal ethanol experience. At each age, the magnitude of the enhanced odor response in demonstrators was similar to that of observers. Interestingly, only re-exposure as a demonstrator resulted in persistence of the behavioral response into adulthood in both sexes. Conclusions:, The method of ethanol re-exposure plays an important role in prolonging the odor-mediated effects of fetal exposure. While ethanol odor-specific exposure through social interaction is important, additional factors such as the pairing of retronasal and hematogenic olfaction with ethanol's intoxicating properties appear necessary to achieve persistence in both sexes. [source]

Ontogeny of the Enhanced Fetal-Ethanol-Induced Behavioral and Neurophysiologic Olfactory Response to Ethanol Odor

ALCOHOLISM, Issue 2 2010
Amber M. Eade
Background:, Studies report a fundamental relationship between chemosensory function and the responsiveness to ethanol, its component orosensory qualities, and its odor as a consequence of fetal ethanol exposure. Regarding odor, fetal exposed rats display enhanced olfactory neural and behavioral responses to ethanol odor at postnatal (P) day 15. Although these consequences are absent in adults (P90), the behavioral effect has been shown to persist into adolescence (P37). Given the developmental timing of these observations, we explored the decay in the response to ethanol odor by examining ages between P37 and young adulthood. Moreover, we sought to determine whether the P15 neurophysiologic effect persists, at least, to P40. Methods:, Behavioral and olfactory epithelial (OE) responses of fetal ethanol exposed and control rats were tested at P40, P50, P60, or P70. Whole-body plethysmography was used to quantify each animal's innate behavioral response to ethanol odor. We then mapped the odorant-induced activity across the OE in response to different odorants, including ethanol, using optical recording methods. Results:, Relative to controls, ethanol exposed animals showed an enhanced behavioral response to ethanol odor that, while significant at each age, decreased in magnitude. These results, in conjunction with previous findings, permitted the development of an ontologic odor response model of fetal exposure. The fitted model exemplifies that odor-mediated effects exist at birth, peak in adolescence and then decline, becoming absent by P90. There was no evidence of an effect on the odor response of the OE at any age tested. Conclusions:, Fetal exposure yields an enhanced behavioral response to ethanol odor that peaks in adolescence and wanes through young adulthood. This occurs absent an enhanced response of the OE. This latter finding suggests that by P40 the OE returns to an ethanol "neutral" status and that central mechanisms, such as ethanol-induced alterations in olfactory bulb circuitry, underlie the enhanced behavioral response. Our study provides a more comprehensive understanding of the ontogeny of fetal-ethanol-induced olfactory functional plasticity and the behavioral response to ethanol odor. [source]

Postnatal downregulation of inhibitory neuromuscular transmission to the longitudinal muscle of the guinea pig ileum

NEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2009
X. Bian
Abstract, Neuromuscular transmission is crucial for normal gut motility but little is known about its postnatal maturation. This study investigated excitatory/inhibitory neuromuscular transmission in vitro using ileal nerve-muscle preparations made from neonatal (,48 h postnatal) and adult (,4 months postnatal) guinea pigs. In tissues from neonates and adults, nicotine (0.3,30 ,mol L,1) contracted longitudinal muscle preparations in a tetrodotoxin (TTX) (0.3 ,mol L,1)-sensitive manner. The muscarinic receptor antagonist, scopolamine (1 ,mol L,1), reduced substantially nicotine-induced contractions in neonatal tissues but not adult tissues. In the presence of N, -nitro- l -arginine (NLA, 100 ,mol L,1) to block nitric oxide (NO) mediated inhibitory neuromuscular transmission, scopolamine-resistant nicotine-induced contractions were revealed in neonatal tissues. NLA enhanced the nicotine-induced contractions in neonatal but not in adult tissues. Electrical field stimulation (20 V; 0.3 ms; 5,25 Hz, scopolamine 1 ,mol L,1 present) caused NLA and TTX-sensitive longitudinal muscle relaxations. Frequency,response curves in neonatal tissues were left-shifted compared with those obtained in adult tissues. Immunohistochemical studies revealed that NO synthase (NOS)-immunoreactivity (ir) was present in nerve fibres supplying the longitudinal muscle in neonatal and adult tissues. However, quantitative studies demonstrated that fluorescence intensity of NOS-ir nerve fibres was higher in neonatal than adult tissues. Nerve fibres containing substance P were abundant in longitudinal muscle in adult but not in neonatal tissues. Inhibitory neuromuscular transmission is relatively more effective in the neonatal guinea pig small intestine. Delayed maturation of excitatory motor pathways might contribute to paediatric motility disturbances. [source]

Aetiology of childhood vision impairment, metropolitan Atlanta, 1991,93

PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 1 2000
Cynthia A. Mervis
Data from the population-based Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) were used to describe the underlying causes of vision impairment (VI; corrected visual acuity in the better eye of 20/70 or worse) in young children (n = 228) in metropolitan Atlanta in 1991,93. Children with VI were identified through record review at multiple educational and medical sources. Children were categorised as having isolated VI or multiple disabilities (i.e. VI plus one or more of four additional developmental disabilities) and as having low vision (visual acuity 20/70,20/400) or blindness (visual acuity worse than 20/400). Medical conditions abstracted from MADDSP sources were reviewed to determine the probable aetiology of a child's VI. Aetiologies were assigned to one of three developmental time periods: prenatal, perinatal, or postnatal. Prenatal aetiologies were identified in 43% of the children; 38% of the prenatal aetiologies were genetic. Perinatal aetiologies were found in 27% of the children. Postnatal aetiologies were rare. Prenatal aetiologies were more common in children with isolated VI; perinatal and postnatal aetiologies were more common in children with multiple disabilities. Children with prenatal aetiologies tended to have less severe vision loss than did children with perinatal or postnatal aetiologies. The distribution varied by birthweight, but did not differ significantly by sex or race. [source]