Home About us Contact
|
Home About us Contact | ||
|
|
||
Maternal Injection (maternal + injection)
Selected AbstractsRecombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A pathway mutant salivary glands in vitroDEVELOPMENTAL DYNAMICS, Issue 10 2010K.L. Wells Abstract Hypohidrotic ectodermal dysplasia (HED) is characterized by defective ectodermal organ development. This includes the salivary glands (SGs), which have an important role in lubricating the oral cavity. In humans and mice, HED is caused by mutations in Ectodysplasin A (Eda) pathway genes. Various phenotypes of the mutant mouse EdaTa/Ta, which lacks the ligand Eda, can be rescued by maternal injection or in vitro culture supplementation with recombinant EDA. However, the response of the SGs to this treatment has not been investigated. Here, we show that the submandibular glands (SMGs) of EdaTa/Ta mice exhibit impaired branching morphogenesis, and that supplementation of EdaTa/Ta SMG explants with recombinant EDA rescues the defect. Supplementation of EdardlJ/dlJ SMGs with recombinant Sonic hedgehog (Shh) also rescues the defect, whereas treatment with recombinant Fgf8 does not. This work is the first to test the ability of putative Eda target molecules to rescue Eda pathway mutant SMGs. Developmental Dynamics 239:2674,2684, 2010. © 2010 Wiley-Liss, Inc. [source] The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2008Tania Vitalis Abstract In the rodent and human embryonic brains, the cerebral cortex and hippocampus transiently express high levels of type 1 cannabinoid receptors (CB1Rs), at a developmental stage when these areas are composed mainly of glutamatergic neurons. However, the precise cellular and subcellular localization of CB1R expression as well as effects of CB1R modulation in this cell population remain largely unknown. We report that, starting from embryonic day 12.5, CB1Rs are strongly expressed in both reelin-expressing Cajal-Retzius cells and newly differentiated postmitotic glutamatergic neurons of the mouse telencephalon. CB1R protein is localized first to somato-dendritic endosomes and at later developmental stages it localizes mostly to developing axons. In young axons, CB1Rs are localized both to the axolemma and to large, often multivesicular endosomes. Acute maternal injection of agonist CP-55940 results in the relocation of receptors from axons to somato-dendritic endosomes, indicating the functional competence of embryonic CB1Rs. The adult phenotype of CB1R expression is established around postnatal day 5. By using pharmacological and mutational modulation of CB1R activity in isolated cultured rat hippocampal neurons, we also show that basal activation of CB1R acts as a negative regulatory signal for dendritogenesis, dendritic and axonal outgrowth, and branching. Together, the overall negative regulatory role in neurite development suggests that embryonic CB1R signaling may participate in the correct establishment of neuronal connectivity and suggests a possible mechanism for the development of reported glutamatergic dysfunction in the offspring following maternal cannabis consumption. [source] Dopaminergic signalling in the rodent neonatal suprachiasmatic nucleus identifies a role for protein kinase A and mitogen-activated protein kinase in circadian entrainmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2002Irina L. Schurov Abstract The circadian clock of the suprachiasmatic nuclei (SCN) of perinatal rodents is entrained by maternally derived cues. The SCN of neonatal Syrian hamsters express high-affinity D1 dopamine receptors, and the circadian activity,rest cycle of pups can be entrained by maternal injection of dopaminergic agonists. The present study sought to characterize the intracellular pathways mediating dopaminergic signalling in neonatal rodent SCN. Both dopamine and the D1 agonist SKF81297 caused a dose-dependent increase in phosphorylation of the transcriptional regulator Ca2+/cyclic AMP response element (CRE) binding protein (CREB) in suprachiasmatic GABA-immunoreactive (-IR) neurons held in primary culture. The D1 antagonist SCH23390 blocked this effect. Dopaminergic induction of pCREB-IR in GABA-IR neurons was also blocked by a protein kinase A (PKA) inhibitor, 5,24, and by the MAPK inhibitor, PD98059, whereas KN-62, an inhibitor of Ca2+/calmodulin-dependent (CAM) kinase II/IV was ineffective. Treatment with NMDA increased the level of intracellular Ca2+ in the cultured primary SCN neurons in Mg2+ -free medium, but SKF81297 did not. Blockade of CaM kinase II/IV with KN-62 inhibited glutamatergic induction of pCREB-IR in GABA-IR neurons, whereas 5,24 was ineffective, confirming the independent action of Ca2+ - and cAMP-mediated inputs on pCREB. SKF81297 caused an increase in pERK-IR in SCN cells, and this was blocked by 5,24, indicative of activation of MAPK via D1/cAMP. These results demonstrate that dopaminergic signalling in the neonatal SCN is mediated via the D1-dependent activation of PKA and MAPK, and that this is independent of the glutamatergic regulation via Ca2+ and CaM kinase II/IV responsible for entrainment to the light/dark cycle. [source] Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheepJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008R. PÉREZ In pregnant sheep at 120,130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 ± 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t˝,). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 ± 0.6 ng/mL) and AUC (89.1 ± 11.4 ng·h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 ± 177.9 mL/kg) and lower values of t˝, (8.0 ± 1.4 h) and mean residence time (8.0 ± 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment. [source] Is Prenatal Glucocorticoid Administration Another Origin Of Adult Disease?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001John P Newnham SUMMARY 1. The intra-uterine environment is now believed to play a major role in the origin of many adult diseases. Illnesses in which there is significant ,programming' before the time of birth include hypertension, diabetes, coronary heart disease and stroke. Acting on a genetic predisposition, intra-uterine triggers appear to programme the individual's metabolism and endocrine milieu and, after birth, these risk factors are then either amplified or minimized by environmental influences. The triggers operative during fetal life that have been studied most extensively are undernutrition and glucocorticoid exposure. 2. Over the past decade, a series of studies in sheep have focused on the perinatal and life-long consequences of glucocorticoid exposure in mid- to late-pregnancy. These studies in the sheep model have shown that maternal injections with glucocorticoids, in a manner similar to clinical treatment for women at risk of preterm birth, enhance fetal lung maturation, but were also associated with developmental and other functional alterations that are of concern. With weekly doses to the mother, there is restricted fetal growth, delayed myelination of the central nervous system, altered blood pressure soon after birth and increased insulin response to glucose challenge in early adulthood. If the glucocorticoids are given to the fetus by ultrasound-guided intramuscular injection, rather than to the mother, the effects on lung maturation are similar, but growth is spared and blood pressure after birth is unaltered. Increased insulin response to glucose challenge occurs in early adulthood with glucocorticoid by either route and is independent of growth restriction. 3. The findings in experimental animals are supported by studies of children in the Western Australian Preterm Infant Follow-up Study. Multivariate analyses have shown that increasing the number of glucocorticoid exposures, for the purpose of enhancing lung maturation prior to preterm birth, is associated with reduced birthweight and behavioural disorders at 3 years of age. 4. The results of these animal and clinical studies provide further support for a role of prenatal glucocorticoid exposure in triggering predisposition to adult disease. Further exploration of these models is expected to uncover the mechanisms and lead to effective strategies that may underpin clinical interventions. [source] | |||||||||||||