scholarly journals Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jacques Gonzales ◽  
Catherine Le Berre-Scoul ◽  
Anne Dariel ◽  
Paul Bréhéret ◽  
Michel Neunlist ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Colonic Motility ◽  
Hirschsprung Disease ◽  
Perinatal Period ◽  
Cellular Level ◽  
Postnatal Period ◽  
Enteric Neurons ◽  
Semaphorin 3A ◽  
Potential Implication ◽  
Synapsin 1

Abstract Most of the gut functions are controlled by the enteric nervous system (ENS), a complex network of enteric neurons located throughout the wall of the gastrointestinal tract. The formation of ENS connectivity during the perinatal period critically underlies the establishment of gastrointestinal motility, but the factors involved in this maturation process remain poorly characterized. Here, we examined the role of Semaphorin 3A (Sema3A) on ENS maturation and its potential implication in Hirschsprung disease (HSCR), a developmental disorder of the ENS with impaired colonic motility. We found that Sema3A and its receptor Neuropilin 1 (NRP1) are expressed in the rat gut during the early postnatal period. At the cellular level, NRP1 is expressed by enteric neurons, where it is particularly enriched at growth areas of developing axons. Treatment of primary ENS cultures and gut explants with Sema3A restricts axon elongation and synapse formation. Comparison of the ganglionic colon of HSCR patients to the colon of patients with anorectal malformation shows reduced expression of the synaptic molecule synapsin 1 in HSCR, which is inversely correlated with Sema3A expression. Our study identifies Sema3A as a critical regulator of ENS connectivity and provides a link between altered ENS connectivity and HSCR.

Update on the Role of Stem Cells in the Treatment of Hirschsprung Disease

2018 ◽  
Vol 28 (03) ◽  
pp. 215-221 ◽  
Author(s):  
Kathy Lui ◽  
Paul Tam ◽  
Elly Ngan
Keyword(s):  
Stem Cells ◽  
Colonic Motility ◽  
Hirschsprung Disease ◽  
Congenital Disorder ◽  
Enteric Neurons ◽  
Somatic Stem Cells ◽  
Self Renewal ◽  
Differentiation Capacity ◽  
Cell Based Therapy ◽  
Adult Tissues

AbstractStem cells possess the ability of self-renewal and the potency to differentiate into multiple cell lineages. Somatic stem cells are present in adult tissues, but they usually exhibit limited differentiation capacity and life span. On the other hand, somatic cells from adult tissues can be reprogrammed into induced pluripotent stem cells (iPSCs) that retain a full differentiation capacity with unlimited self-renewal ability. Autologous origin of iPSCs makes them an ideal source of cells for regenerative medicine to replenish the missing or damaged cells in the patients. iPSCs nowadays have also been widely used to build human disease models to study pathological mechanisms of the diseases. Hirschsprung disease (HSCR) is a congenital disorder caused by defects in the development of enteric neural crest stem cells. The failures of the ENCCs to proliferate, differentiate, and/or migrate lead to the absence of enteric neurons in the distal colon, resulting in colonic motility dysfunction. The lack of effective treatment for HSCR urges continuous efforts to develop new therapies for this congenital disorder. In this review, we will discuss the potential applications of somatic stem cells and iPSCs for the cell-based therapy of HSCR. We will also highlight the recent advances in stem cell research for the establishment of human HSCR models for the development of novel therapies.

Developmental changes in nitric oxide synthase isoform expression and nitric oxide production in fetal baboon lung

2002 ◽  
Vol 283 (6) ◽  
pp. L1192-L1199 ◽  
Author(s):  
Philip W. Shaul ◽  
Sam Afshar ◽  
Linda L. Gibson ◽  
Todd S. Sherman ◽  
Jay D. Kerecman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Critical Role ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Developmental Changes ◽  
No Production ◽  
Third Trimester ◽  
Isoform Expression ◽  
Oxide Synthase ◽  
Nos Isoforms

Nitric oxide (NO), produced by NO synthase (NOS), plays a critical role in multiple processes in the lung during the perinatal period. To better understand the regulation of pulmonary NO production in the developing primate, we determined the cell specificity and developmental changes in NOS isoform expression and action in the lungs of third-trimester fetal baboons. Immunohistochemistry in lungs obtained at 175 days (d) of gestation (term = 185 d) revealed that all three NOS isoforms, neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), are primarily expressed in proximal airway epithelium. In proximal lung, there was a marked increase in total NOS enzymatic activity from 125 to 140 d gestation due to elevations in nNOS and eNOS, whereas iNOS expression and activity were minimal. Total NOS activity was constant from 140 to 175 d gestation, and during the latter stage (160–175 d gestation), a dramatic fall in nNOS and eNOS was replaced by a rise in iNOS. Studies done within 1 h of delivery at 125 or 140 d gestation revealed that the principal increase in NOS during the third trimester is associated with an elevation in exhaled NO levels, a decline in expiratory resistance, and greater pulmonary compliance. Thus, there are developmental increases in pulmonary NOS expression and NO production during the early third trimester in the primate that may enhance airway and parenchymal function in the immediate postnatal period.

Perinatal hyperoxia for 14 days increases nerve conduction time and the acute unitary response to hypoxia of rat carotid body chemoreceptors

2005 ◽  
Vol 99 (1) ◽  
pp. 114-119 ◽  
Author(s):  
David F. Donnelly ◽  
Insook Kim ◽  
Claire Carle ◽  
John L. Carroll
Keyword(s):  
Functional Impairment ◽  
Nerve Conduction ◽  
Single Unit ◽  
Acute Hypoxia ◽  
Adult Life ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Conduction Time ◽  
Activity Levels

Hyperoxia in the immediate perinatal period, but not in adult life, is associated with a life-long impairment of the ventilatory response to acute hypoxia. This effect is attributed to a functional impairment of peripheral chemoreceptors, including a reduction in the number of chemoreceptor afferent fibers and a reduction in “whole nerve” afferent activity. The purpose of the present study was to assess the activity levels of single chemoreceptor units in the immediate posthyperoxic period to determine whether functional impairment extended to single chemoreceptor units and whether the impairment was only induced by hyperoxia exposure in the immediate postnatal period. Two groups of rat pups were exposed to 60% inspired O2 fraction for 2 wk at ages 0–14 days and 14–28 days, at which time single-unit activities were isolated and recorded in vitro. Compared with control pups, hyperoxia-treated pups had a 10-fold reduction in baseline (normoxia) spiking activity. Peak unit responses to 12, 5, and 0% O2 were reduced and nerve conduction time was significantly slower in both hyperoxia-treated groups compared with control groups. We conclude that 1) hyperoxia greatly reduces single-unit chemoreceptor activities during normoxia and acute hypoxia, 2) the treatment effect is not limited to the immediate newborn period, and 3) at least part of the impairment may be due to changes in the afferent axonal excitability.

scholarly journals Scorpion Envenomation of Lactating Rats Decreases the Seizure Threshold in Offspring

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 853
Author(s):  
Marina de Oliveira Rodrigues Barbosa ◽  
Maria Eliza F. do Val de Paulo ◽  
Ana Leonor Abrahão Nencioni
Keyword(s):  
Perinatal Period ◽  
Postnatal Period ◽  
Seizure Threshold ◽  
Long Term Effects ◽  
Crude Venom ◽  
Long Time ◽  
Few Data ◽  
The Relationship ◽  
Convulsive Threshold

Few data are available in the literature describing the long-term effects of envenoming in the perinatal period. In this study, the relationship between envenoming of lactating rats and possible behavioral changes in the mother and in her offspring were investigated. Lactating Wistar rats received a single dose of T. serrulatus crude venom on postnatal days 2 (V2), 10 (V10) or 16 (V16), and had their maternal behavior evaluated. The seizure threshold was evaluated in adulthood offspring. A decrease in maternal care during envenoming was observed in V2 and V10 groups. The retrieval behavior was absent in the V2 group, and a lower seizure threshold in the adult offspring of all groups was observed. During envenoming, mothers stayed away from their offspring for a relatively long time. Maternal deprivation during the early postnatal period is one of the most potent stressors for pups and could be responsible, at least in part, for the decrease in the convulsive threshold of the offspring since stress is pointed to as a risk factor for epileptogenesis. Furthermore, the scorpionic accident generates an intense immune response, and inflammation in neonates increases the susceptibility to seizures in adulthood. Therefore, maternal envenoming during lactation can have adverse effects on offspring in adulthood.

scholarly journals Exploring the transition into fatherhood: behavioral, hormonal, and neural underpinnings of responses to infant crying

2020 ◽  
Author(s):  
Kim Alyousefi-van Dijk ◽  
Sandra Thijssen ◽  
Anna Elisabeth van 't Veer ◽  
Renate S. M. Buisman ◽  
Marinus H. van IJzendoorn ◽  
...  
Keyword(s):  
Paternal Care ◽  
Longitudinal Design ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Neural Activation ◽  
Neural Responses ◽  
Parental Sensitivity ◽  
Infant Crying ◽  
Neural Underpinnings ◽  
First Time

In the present hypothesis generating study, behavioral and neural responses to infant crying, as well as paternal hormone levels, were measured in both the prenatal and early postnatal period. Using a longitudinal design, we investigated parental sensitivity, handgrip force, and neural activation in response to infant crying sounds, in addition to testosterone baseline levels, in 25 first-time fathers. We describe the extent to which these aspects of paternal care are related across the perinatal period. The current exploratory study adds to the understudied field of early paternal care by making recommendations, and proposing hypotheses for future studies.

scholarly journals A cellular defense memory imprinted by early life toxic stress

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Eszter Gecse ◽  
Beatrix Gilányi ◽  
Márton Csaba ◽  
Gábor Hajdú ◽  
Csaba Sőti
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Perinatal Period ◽  
Cellular Level ◽  
Adult Survival ◽  
Transcriptional Responses ◽  
C Elegans ◽  
Cellular Defense ◽  
Bacterial Lawn

AbstractStress exposure early in life is implicated in various behavioural and somatic diseases. Experiences during the critical perinatal period form permanent, imprinted memories promoting adult survival. Although imprinting is widely recognized to dictate behaviour, whether it actuates specific transcriptional responses at the cellular level is unknown. Here we report that in response to early life stresses, Caenorhabditis elegans nematodes form an imprinted cellular defense memory. We show that exposing newly-born worms to toxic antimycin A and paraquat, respectively, stimulates the expression of toxin-specific cytoprotective reporters. Toxin exposure also induces avoidance of the toxin-containing bacterial lawn. In contrast, adult worms do not exhibit aversive behaviour towards stress-associated bacterial sensory cues. However, the mere re-encounter with the same cues reactivates the previously induced cytoprotective reporters. Learned adult defenses require memory formation during the L1 larval stage and do not appear to confer increased protection against the toxin. Thus, exposure of C. elegans to toxic stresses in the critical period elicits adaptive behavioural and cytoprotective responses, which do not form imprinted aversive behaviour, but imprint a cytoprotective memory. Our findings identify a novel form of imprinting and suggest that imprinted molecular defenses might underlie various pathophysiological alterations related to early life stress.

Novel recordings of renal sympathetic nerve activity in conscious fetal sheep and newborn lambs

1990 ◽  
Vol 258 (1) ◽  
pp. F218-F221 ◽  
Author(s):  
F. G. Smith ◽  
J. M. Klinkefus ◽  
U. C. Kopp ◽  
J. E. Robillard
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Left Renal Artery ◽  
Nerve Activity ◽  
Fetal Sheep ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sympathetic

This study describes a technique for measuring efferent renal sympathetic nerve activity (RSNA) during the perinatal period. Experiments were carried out in four chronically instrumented fetal sheep (gestational age, 134–140 days) and 6 newborn lambs (postnatal age, 3–7 days). Surgery, performed under halothane anesthesia, consisted of routine catheter insertions and placement of a Doppler flow probe around the left renal artery. In addition, bipolar platinum electrodes were placed on a branch of the left renal postganglionic nerve. At least 24 h after surgery RSNA was measured in conscious fetal and newborn animals. RSNA was pulse synchronous, reduced with pressor agents, and completely inhibited during ganglionic blockade. Using this method, we have provided direct evidence of efferent renal sympathetic nerve traffic in utero and in the immediate postnatal period. This technique opens new avenues into the investigation of the role of the sympathetic nervous system during the perinatal period.

Stimulation of gastric proteases in the neonatal pig by a rise in adrenocortical secretion at parturition

1995 ◽  
Vol 7 (5) ◽  
pp. 1293 ◽  
Author(s):  
PT Sangild
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Late Gestation ◽  
Cortisol Secretion ◽  
Adrenocortical Activity ◽  
Pepsinogen A ◽  
Newborn Pigs ◽  
Neonatal Pig ◽  
Stimulation Of

In many species adrenocortical activity and glucocorticoid secretion increase in late gestation and reach a peak at birth. In this study, we investigated the hypothesis that glucocorticoids stimulate the synthesis of gastric protease zymogens in the perinatal period of pigs. Pigs were delivered by Caesarean section 3-4 days prior to term (to circumvent the natural cortisol surge) and treated daily with either saline (n = 11), metyrapone (an inhibitor of cortisol synthesis, n = 12), adrenocorticotropic hormone (ACTH, n = 14) or cortisol-acetate (n = 6). The pigs were killed at 3 or 6-7 days of age and concentrations of protease zymogens in gastric mucosal extracts determined by electroimmunoassay. Zymogen contents were also determined in control (untreated) pigs from one week before birth to four weeks after birth. In control pigs, concentration of prochymosin increased rapidly before term, peaked at birth, and decreased in the postnatal period; concentrations of pepsinogen A, pepsinogen B and progastricsin were low in newborn pigs and increased in the weeks after birth. Caesarean-delivered pigs injected with saline had lower concentrations of prochymosin and pepsinogen A at 6-7 days than vaginally delivered pigs of the same postnatal age. The concentrations of these zymogens were further reduced after metyrapone treatment (depressed cortisol secretion) but were increased after treatment with ACTH (stimulated cortisol secretion) or cortisol-acetate (exogenous glucocorticoid). No consistent effects were observed for the two minor gastric protease zymogens in the pig, pepsinogen B and progastricsin. The results suggest that the normal pre-partum surge in circulating cortisol stimulates the development of the major gastric protease zymogens in the pig, prochymosin and pepsinogen A.

Lung hyaluronan during development: a quantitative and morphological study

1991 ◽  
Vol 260 (5) ◽  
pp. H1449-H1454 ◽  
Author(s):  
S. J. Allen ◽  
E. Gunnar Sedin ◽  
A. Jonzon ◽  
A. F. Wells ◽  
T. C. Laurent
Keyword(s):  
Morphological Study ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Late Gestation ◽  
Visceral Pleura ◽  
Predominant Role ◽  
Neonatal Lung ◽  
Important Constituent ◽  
Migrating Cells

Hyaluronan, an important constituent of developmental interstitium in fetal lungs, mediates cell-to-cell interactions and thereby directs migrating cells. Furthermore, because of the polyionic nature of the molecule, hyaluronan forms open, hydrated matrices that provide channels for migrating cells. This hydrated matrix undergoes contraction before birth. However, continued growth of the lung in the perinatal period requires newly synthesized hyaluronan. This study's purpose was to elucidate the changes in lung hyaluronan concentration and distribution in the perinatal period. We studied rabbits at days -6, -4, -2, -1, 0, +2, and +4 with respect to term, as well as adult rabbits. We found that hyaluronan concentration was highest in the youngest fetuses studied [682 +/- 115 micrograms/g dry wt (means +/- SD)]. However, hyaluronan concentration decreased to 129 +/- 12 micrograms/g dry wt just before birth then returned to 366 +/- 111 micrograms/g dry wt at day +4; these values were similar to adult values. We found hyaluronan staining decreased during late gestation, particularly in the interalveolar region. In the postnatal period, hyaluronan staining increased in the visceral pleura and, to a lesser extent, beneath the epithelium of the bronchioles. Hyaluronan did not reaccumulate in the interalveolar region in the postnatal period. Our data suggest a change in the predominant role of lung hyaluronan during the perinatal period. Before term, hyaluronan facilitates morphogenesis. However, hyaluronan's major role in neonatal lung is most likely in regulation of fluid balance in interstitium.

scholarly journals Preconditioning and Postinsult Therapies for Perinatal Hypoxic–Ischemic Injury at Term

2010 ◽  
Vol 113 (1) ◽  
pp. 233-249 ◽  
Author(s):  
Robert D. Sanders ◽  
Helen J. Manning ◽  
Nicola J. Robertson ◽  
Daqing Ma ◽  
A. David Edwards ◽  
...  
Keyword(s):  
Perinatal Period ◽  
Rapid Identification ◽  
Postnatal Period ◽  
Hypoxic Ischemic Encephalopathy ◽  
Current Status ◽  
Neuroprotective Agents ◽  
Period 2 ◽  
Neuroprotective Strategies ◽  
The Brain ◽  
Ischemic Encephalopathy

Perinatal hypoxic-ischemic encephalopathy can be a devastating complication of childbirth. Herein, the authors review the pathophysiology of hypoxic-ischemic encephalopathy and the current status of neuroprotective strategies to ameliorate the injury centering on four themes: (1) monitoring in the perinatal period, (2) rapid identification of affected neonates to allow timely institution of therapy, (3) preconditioning therapy (a therapeutic that reduces the brain vulnerability) before hypoxic-ischemic encephalopathy, and (4) prompt institution of postinsult therapies to ameliorate the evolving injury. Recent clinical trials have demonstrated the significant benefit for hypothermic therapy in the postnatal period; furthermore, there is accumulating preclinical evidence that adjunctive therapies can enhance hypothermic neuroprotection. Advances in the understanding of preconditioning may lead to the administration of neuroprotective agents earlier during childbirth. Although most of these neuroprotective strategies have not yet entered clinical practice, there is a significant hope that further developments will enhance hypothermic neuroprotection.

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