Explore the vast range of titles available.

The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1α impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1α for development of the sympathetic nervous system.

This study presents, for the first time, a histomorphological analysis of the lumbar sympathetic chain ganglia (LSChG) during prenatal development in 5-, 7-, and 10-week-old female porcine foetuses. Single immunohistochemical staining for protein gene product 9.5 (PGP) as a neural marker revealed progressive growth and differentiation of ganglia and neurons. In 5-week-old foetuses, ganglia were small paired structures composed of oval neurons with large nuclei. By seven weeks, both ganglia and neurons increased in size and adopted a more rounded morphology. At 10 weeks, ganglia showed marked enlargement and morphological diversity, with neurons varying in shape and size. These findings indicate functional maturation of the sympathetic chain ganglia, relevant to autonomic innervation of abdominal and pelvic viscera, and may support early diagnosis of neurodevelopmental disorders and improvements in prenatal veterinary care.

The extracellular calcium-sensing receptor (CaSR) monitors the systemic, extracellular, free ionized-calcium level ([Ca 2+ ] o ) in organs involved in systemic [Ca 2+ ] o homeostasis. However, CaSR is also expressed in the nervous system, where its role is unknown. We found large amounts of CaSR in perinatal mouse sympathetic neurons when their axons were innervating and branching extensively in their targets. Manipulating CaSR function in these neurons by varying [Ca 2+ ] o , using CaSR agonists and antagonists, or expressing a dominant-negative CaSR markedly affected neurite growth in vitro . Sympathetic neurons lacking CaSR had smaller neurite arbors in vitro , and sympathetic innervation density was reduced in CaSR-deficient mice in vivo . Hippocampal pyramidal neurons, which also express CaSR, had smaller dendrites when transfected with dominant-negative CaSR in postnatal organotypic cultures. Our findings reveal a crucial role for CaSR in regulating the growth of neural processes in the peripheral and central nervous systems.

The diversity of neurons in sympathetic ganglia and dorsal root ganglia (DRG) provides intriguing systems for the analysis of neuronal differentiation. Cell surface receptors for the GDNF family ligands (GFLs) glial cell-line-derived neurotrophic factor (GDNF), neurturin and artemin, are expressed in subpopulations of these neurons prompting the question regarding their involvement in neuronal subtype specification. Mutational analysis in mice has demonstrated the requirement for GFL signalling during embryonic development of cholinergic sympathetic neurons as shown by the loss of expression from the cholinergic gene locus in ganglia from mice deficient for ret, the signal transducing subunit of the GFL receptor complex. Analysis in mutant animals and transgenic mice overexpressing GFLs demonstrates an effect on sensitivity to thermal and mechanical stimuli in DRG neurons correlating at least partially with the altered expression of transient receptor potential ion channels and acid-sensitive cation channels. Persistence of targeted cells in mutant ganglia suggests that the alterations are caused by differentiation effects and not by cell loss. Because of the massive effect of GFLs on neurite outgrowth, it remains to be determined whether GFL signalling acts directly on neuronal specification or indirectly via altered target innervation and access to other growth factors. The data show that GFL signalling is required for the specification of subpopulations of sensory and autonomic neurons. In order to comprehend this process fully, the role of individual GFLs, the transduction of the GFL signals, and the interplay of GFL signalling with other regulatory pathways need to be deciphered.

Doc number: 16 Abstract Background: Neurons in sympathetic ganglia and neuroendocrine cells in the adrenal medulla share not only their embryonic origin from sympathoadrenal precursors in the neural crest but also a range of functional features. These include the capacity for noradrenaline biosynthesis, vesicular storage and regulated release. Yet the regulation of neuronal properties in early neuroendocrine differentiation is a matter of debate and the developmental expression of the vesicle fusion machinery, which includes components found in both neurons and neuroendocrine cells, is not resolved. Results: Analysis of synaptic protein and pan-neuronal marker mRNA expression during mouse development uncovers profound differences between sympathetic neurons and adrenal chromaffin cells, which result in qualitatively similar but quantitatively divergent transcript profiles. In sympathetic neurons embryonic upregulation of synaptic protein mRNA follows early and persistent induction of pan-neuronal marker transcripts. In adrenal chromaffin cells pan-neuronal marker expression occurs only transiently and synaptic protein messages remain at distinctly low levels throughout embryogenesis. Embryonic induction of synaptotagmin I (Syt1) in sympathetic ganglia and postnatal upregulation of synaptotagmin VII (Syt7) in adrenal medulla results in a cell type-specific difference in isoform prevalence. Dicer 1 inactivation in catecholaminergic cells reduces high neuronal synaptic protein mRNA levels but not their neuroendocrine low level expression. Pan-neuronal marker mRNAs are induced in chromaffin cells to yield a more neuron-like transcript pattern, while ultrastructure is not altered. Conclusions: Our study demonstrates that remarkably different gene regulatory programs govern the expression of synaptic proteins in the neuronal and neuroendocrine branch of the sympathoadrenal system. They result in overlapping but quantitatively divergent transcript profiles. Dicer 1-dependent regulation is required to establish high neuronal mRNA levels for synaptic proteins and to maintain repression of neurofilament messages in neuroendocrine cells.

The neurotransmitter composition of neurons in the cranial cervical ganglion (CCG) and celiac ganglia (CG) in rats of different ages (neonatal, 10, 12, 30, and 60 days) was studied by immunohistochemical methods. The results showed that most neurons in these sympathetic ganglia contain tyrosine hydroxylase (TH). Most TH-positive neurons were also neuropeptide Y (NPY)-positive. In all ganglia, the proportions of neurons containing NPY increased from the moment of birth to the end of the first month of life. In the CG, NPY was present in a significantly greater proportion of neurons than in the CCG. Substance P, vasoactive intestinal peptide, and choline acetyltransferase were present in occasional neurons in the CCG and CG from birth. There was no change in the proportion of this type of neuron with age. Definitive establishment of the neurotransmitter composition in the sympathetic ganglia studied here occurred by the end of the first month of life.

During the development of the female rat, a maturing process of the factors that regulate the functioning of the ovaries takes place, resulting in different responses according to the age of the animal. Studies show that peripheral innervation is one relevant factor involved. In the present study we analyzed the anatomical relationship between the neurons in the celiac-superior mesenteric ganglia (CSMG), and the right or left ovary in 24 or 28 days old female pre-pubertal rats. The participation of the superior ovarian nerve (SON) in the communication between the CSMG and the ovaries was analyzed in animals with unilateral section of the SON, previous to injecting true blue (TB) into the ovarian bursa. The animals were killed seven days after treatment. TB stained neurons were quantified at the superior mesenteric-celiac ganglia. The number of labeled neurons in the CSMG of rats treated at 28 days of age was significantly higher than those treated on day 24. At age 24 days, injecting TB into the right ovary resulted in neuron stains on both sides of the celiac ganglia; whereas, injecting the left side the stains were exclusively ipsilateral. Such asymmetry was not observed when the rats were treated at age of 28 days. In younger rats, sectioning the left SON resulted in significantly lower number of stained neurons in the left ganglia while sectioning the right SON did not modify the number of stained neurons. When sectioning of the SON was performed to 28 days old rats, no staining was observed. Present results show that the number and connectivity of post-ganglionic neurons of the CSMG connected to the ovary of juvenile female rats change as the animal mature; that the SON plays a role in this communication process as puberty approaches; and that this maturing process is different for the right or the left ovary.

Human and porcine fetal airways have been shown to contract spontaneously from the first trimester, the latter also contracting in response to neural stimulation. Our object was to map immunohistochemically the innervation and its relationship to the airway smooth muscle (ASM) in the human fetal lung from early gestation to the postnatal period. Whole mounts of the bronchial tree were stained with antibodies to the pan-neuronal marker protein gene product 9.5, the Schwann cell marker S-100, and the ASM contractile protein alpha-actin, and imaged using confocal microscopy. By the end of the embryonic period (53 d gestation), the branching epithelial tubules in the primordial lung were covered with ASM to the base of the terminal sacs. An extensive plexus of nerve trunks containing nerve bundles, forming ganglia, and Schwann cells ensheathed the ASM. By 16 wk (canalicular stage), maturation of the innervation was advanced with two major nerve trunks running the length of the bronchial tree, giving rise to varicosed fibers lying on the ASM. An extensive nerve plexus in the mucosa was also present. The distal airways of infants who had died of Sudden Infant Death Syndrome were also covered with smooth muscle and were well innervated. Thus, an essentially complete coat of ASM and an abundant neural plexus ensheathing the airways are an integral part of the branching epithelial tubules from early in lung development.

The locations and morphometric characteristics of NADPH-diaphorase (NADPH-d)-positive neurons were identified in the cranial cervical (CCG), stellate (SG), and celiac (CG) ganglia in neonatal rats, mice, and cats and animals aged 10, 20, 30, 60, and 180 days. No NADPH-d-positive neurons were found in rats and mice in any of the age groups studied. In kittens, the majority of NADPH-d-positive neurons were located in the SG, with fewer in the CCG and only occasional neurons in the CG, regardless of age. The proportion of NADPH-d-positive neurons in the SG increased during the first 20 days of life and decreased after 30 days, to the end of the second month of life. The proportion of NADPH-d-reactive neurons in the CCG and CG did not change during ontogenesis. The mean sizes of NADPH-d-positive neurons in different ganglia in animals of the same age were not significantly different. These data lead to the conclusion that the development of NADPH-d-positive neurons with age occurs heterochronously and is complete by the end of the second month of life.

A method based on retrograde axonal transport of horseradish peroxidase was used to study the efferent innervation of the cervical segment of the trachea in neonatal kittens and kittens aged 10, 20, and 30 days and two months. Labeled neurons in all animals were located in the cranial cervical, middle cervical, and cervicothoracic sympathetic ganglia on the right and left sides, at the level of the medulla oblongata, and in the dorsal and ambiguus nuclei of the vagus nerves. Up to age 30 days, neurons were also seen in the ventral horns of the spinal cord in segments C1 to C5. The number of sympathetic neurons innervating the trachea increased from the moment of birth, reaching a maximum by 10–20 days and then decreasing to age two months. The number of parasympathetic neurons gradually decreased during ontogenesis.