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At least 793 records · Page 44Linked to original sources
PubMed2006

The inhibitory effects of local anesthetics on primary sensory nerve and parasympathetic nerve in rabbit eye.

Primary sensory nerves transmit information to both the periphery and central nervous systems, and they mediate neurogenic inflammation by release of neurotransmitters, such as tachykinins, in the periphery. Because the effect of local anesthetics on neurogenic inflammation is a subject of controversy, we investigated the direct effect of local anesthetics on tachykininergic neurotransmission, comparing it with cholinergic neurotransmission in the rabbit iris sphincter muscle. Rabbit iris sphincter muscle is innervated by trigeminal tachykininergic and parasympathetic cholinergic nerves, and the electrical transmural stimulation produces tachykininergic and cholinergic contractions. Cocaine and lidocaine (1-300 microM) attenuated tachykininergic and cholinergic contractions induced by electrical transmural stimulation in concentration- and stimulus frequency-dependent manner. However, the sensitivity to both local anesthetics was slightly, but significantly, higher in tachykininergic than in cholinergic responses. Exogenous neurokinin A and carbachol produced contractions that were not inhibited by 100 microM of cocaine and lidocaine. These results show that local anesthetics have a direct inhibitory effect on tachykininergic neurotransmission of the trigeminal sensory nerve, and the effect on this nerve is more potent than on the parasympathetic nerve and suggests that local anesthetics may have antineurogenic inflammatory effects via the inhibitory effects on the peripheral transmission of primary sensory nerve.

Anesthetics, Local↗
PubMed1998

MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity.

We have investigated the genetic circuitry underlying the determination of neuronal identity, using mammalian peripheral autonomic neurons as a model system. Previously, we showed that treatment of neural crest stem cells (NCSCs) with bone morphogenetic protein-2 (BMP-2) leads to an induction of MASH1 expression and consequent autonomic neuronal differentiation. We now show that BMP2 also induces expression of the paired homeodomain transcription factor Phox2a, and the GDNF/NTN signalling receptor tyrosine kinase c-RET. Constitutive expression of MASH1 in NCSCs from a retroviral vector, in the absence of exogenous BMP2, induces expression of both Phox2a and c-RET in a large fraction of infected colonies, and also promotes morphological neuronal differentiation and expression of pan-neuronal markers. In vivo, expression of Phox2a in autonomic ganglia is strongly reduced in Mash1 -/- embryos. These loss- and gain-of-function data suggest that MASH1 positively regulates expression of Phox2a, either directly or indirectly. Constitutive expression of Phox2a, by contrast to MASH1, fails to induce expression of neuronal markers or a neuronal morphology, but does induce expression of c-RET. These data suggest that MASH1 couples expression of pan-neuronal and subtype-specific components of autonomic neuronal identity, and support the general idea that identity is established by combining subprograms involving cascades of transcription factors, which specify distinct components of neuronal phenotype.

Animals↗
PubMed2001

Slit signaling promotes the terminal asymmetric division of neural precursor cells in the Drosophila CNS.

The bipotential Ganglion Mother Cells, or GMCs, in the Drosophila CNS asymmetrically divide to generate two distinct post-mitotic neurons. Here, we show that the midline repellent Slit (Sli), via its receptor Roundabout (Robo), promotes the terminal asymmetric division of GMCs. In GMC-1 of the RP2/sib lineage, Slit promotes asymmetric division by down regulating two POU proteins, Nubbin and Mitimere. The down regulation of these proteins allows the asymmetric localization of Inscuteable, leading to the asymmetric division of GMC-1. Consistent with this, over-expression of these POU genes in a late GMC-1 causes mis-localization of Insc and symmetric division of GMC-1 to generate two RP2s. Similarly, increasing the dosage of the two POU genes in sli mutant background enhances the penetrance of the RP2 lineage defects whereas reducing the dosage of the two genes reduces the penetrance of the phenotype. These results tie a cell-non-autonomous signaling pathway to the asymmetric division of precursor cells during neurogenesis.

Animals↗
PubMed2002

Comparison of the generic neuronal differentiation and neuron subtype specification functions of mammalian achaete-scute and atonal homologs in cultured neural progenitor cells.

In the vertebrate peripheral nervous system, the proneural genes neurogenin 1 and neurogenin 2 (Ngn1 and Ngn2), and Mash1 are required for sensory and autonomic neurogenesis, respectively. In cultures of neural tube-derived, primitive PNS progenitors NGNs promote expression of sensory markers and MASH1 that of autonomic markers. These effects do not simply reflect enhanced neuronal differentiation, suggesting that both bHLH factors also specify neuronal identity like their Drosophila counterparts. At high concentrations of BMP2 or in neural crest stem cells (NCSCs), however, NGNs like MASH1 promote only autonomic marker expression. These data suggest that that the identity specification function of NGNs is more sensitive to context than is that of MASH1. In NCSCs, MASH1 is more sensitive to Notch-mediated inhibition of neurogenesis and cell cycle arrest, than are the NGNs. Thus, the two proneural genes differ in other functional properties besides the neuron subtype identities they can promote. These properties may explain cellular differences between MASH1- and NGN-dependent lineages in the timing of neuronal differentiation and cell cycle exit.

Animals↗
PubMed1995

[Pulmonary and pulmonary-related reflexes mediated by serotonin receptors in the peripheral nervous system].

It is known that serotonin is widely distributed in the body; its receptors are located in various tissues and organs. It has been reported that serotonin receptors without apparent synaptic structure exist in the peripheral nervous system. These serotonin receptors might be the target of circulatory serotonin. In particular, serotonin has a potent depolarizing action on vagal afferent nerves. This stimulation causes various autonomic reflexes, so-called von Bezold-Jarisch reflex, that consist of bradycardia, hypotension and apnea. The peripheral 5-HT3-receptor subtype seems to be responsible for the initiation of these reflexes. The physiological and pathophysiological significance of these serotonin-induced modulations have not, however, been established. The present study was designed to examine the effects of exogenous serotonin on the chemosensitive afferent nerves including carotid sinus nerves, cervical vagus nerve, and efferent motor nerves, such as phrenic nerves and pharyngeal nerves. Because little is known about the involvement of the serotonergic system in the pulmonary reflex and pulmonary-related reflexes (swallowing or vomiting), the distribution of the motor component of these nerves within the brain stem of the rat was also determined.

Animals↗
PubMed2004

[Role of VIP-neurons in the hypothalamic suprachiasmatic nucleus in the control of blood glucose].

The hypothalamic suprachiasmatic nucleus (SCN), a master circadian oscillator in mammals, contains VIP-neurons. In our study on the mechanism of the central regulation of glucose metabolism in rats, we obtained following results: 1) intracranial injection of either 2-deoxy-D-glucose (2DG) or VIP elicited hyperglycemia by enhancing neural activities of the sympathetic nerves and by the suppression of the insulin secretion and enhances of secretions of adrenaline and glucagon; 2) bilateral lesions of the SCN eliminated the hyperglycemia and sympathetic excitation induced by intracranial injection of 2DG, and intracranial administration of VIP restored the 2DG-hyperglycemia; 3) infusion of VIP-antisense oligo in the SCN reduced the VIP content in the SCN and abolished the 2DG-hyperglycemia, and intracranial injection of VIP restored the 2DG-hyperglycemia in rats infused the VIP-antisense oligo; 4) intrapancreatic injection of pseudorabies virus (PRV, Bartha), which is retrogradedly transported, caused the transfer of PRV to VIP-neurons in the SCN, and denervations of both the sympathetic and parasympathetic nerves innervating the pancreas eliminated the retrograde transport of PRV to VIP-neurons in the SCN. These findings suggest that VIP-neurons in the SCN regulate the blood glucose level through the enhancement of the sympathetic activity.

Animals↗
PubMed2001

Dominant anti-vagal effect of pentobarbital on cardiac responses to intracardiac autonomic nerve stimulation in the dog.

The isolated canine atrium was perfused by heparinized blood of the donor dog. An adequate dose of pentobarbital that induced a potent hypotension in the donor did not produce any significant change in the atrial rate and developed tension in the isolated atrium perfused with donor's blood. Pentobarbital in doses that modified neither cardiac responses to intracardiac adrenergic nerve stimulation nor exogenously given norepinephrine or acetylcholine significantly inhibited intracardiac vagal responses. From these results, it is concluded that a large dose of pentobarbital has a dominant antivagal effect in the heart.

Animals↗
PubMed1986

Regeneration of the eight cranial nerve. I. Anatomic verification in the bullfrog.

The regenerative capacity of the eight cranial nerve of the bullfrog, Rana catesbeiana, was investigated. The nerve was sectioned between the ganglion and the brain stem in 16 experimental animals. Horseradish peroxidase was extracellularly injected distal to the site of the nerve section five or more weeks postoperatively. Labeled fibers were identified histologically and their central nervous system projections studied. The findings were as follows: 1. The eight cranial nerve of the bullfrog regenerated after preganglionic axotomy. 2. Fibers of all sizes regenerated. The regenerated fibers in the nerve were disorderly at the site of nerve section. Most fibers entered the brain stem and formed a vestibuloauditory tract, although some "escaped" and coursed along the brain stem. 3. The regenerated vestibuloauditory tract was situated more laterally than normal, with thick and thin fibers intermixed. 4. Regenerated tertiary fibers were long and tortuous and had unusual trajectories. 5. All vestibuloauditory nuclei received thick and thin afferent fibers.

Animals↗
PubMed2004

Extreme stretch growth of integrated axons.

Large animals can undergo enormous growth during development, suggesting that axons in nerves and white matter tracts rapidly expand as well. Because integrated axons have no growth cones to extend from, it has been postulated that mechanical forces may stimulate axon elongation matching the growth of the animal. However, this distinct form of rapid and sustained growth of integrated axons has never been demonstrated. Here, we used a microstepper motor system to evaluate the effects of escalating rates of stretch on integrated axon tracts over days to weeks in culture. We found that axon tracts could be stretch grown at rates of 8 mm/d and reach lengths of 10 cm without disconnection. Despite dynamic and long-term elongation, stretched axons increased in caliber by 35%, while the morphology and density of cytoskeletal constituents and organelles were maintained. These data provide the first evidence that mechanical stimuli can induce extreme "stretch growth" of integrated axon tracts, far exceeding any previously observed limits of axon growth.

Animals↗
PubMed2006

Biology, clinical relevance, and molecularly targeted therapy in acute leukemia with FLT3 mutation.

Overexpression and activating mutations of receptor tyrosine kinases (RTKs) are known to be involved in the pathophysiology of several kinds of cancer cells. FMS-like receptor tyrosine kinase 3 (FLT3), together with KIT, FMS, and platelet-derived growth factor receptor, is a class III RTK. FLT3 mutations were first reported as internal tandem duplication (FLT3/ITD) of the juxtamembrane domain-coding sequence; subsequently, a missense point mutation at the D835 residue and point mutations, deletions, and insertions in the codons surrounding D835 within a FLT3 tyrosine kinase domain (FLT3/KDMs) have been found. FLT3 mutations are the most frequent genetic alterations so far reported in acute myeloid leukemia and are involved in the signaling pathway of autonomous proliferation and differentiation block in leukemia cells. Several large-scale studies have confirmed that FLT3/ITD is strongly associated with leukocytosis and a poor prognosis. Therefore, routine screening for FLT3 mutations is recommended to stratify patients into distinct risk groups. However, because high-dose chemotherapy and stem cell transplantation cannot overcome the adverse effects of FLT3 mutations, the development of FLT3 kinase inhibitors is expected to produce a more efficacious therapeutic strategy for leukemia therapy.

Acute Disease↗
PubMed2003

Autonomic nerves terminating on smooth muscle cells of vessels in the pineal organ of various mammals.

The significance of autonomic nerves reaching the pincal organ was already investigated in connection to the innervation of pinealocytes and mediating light information from the retina for periodic melatonin secretion. In earlier works we found that some autonomic nerve fibers are not secretomotor but terminate on arteriolar smooth muscle cells in the pineal organ of the mink (Mustela vison). Studying in serial sections the pineal organ of the mink and 15 other mammalian species in the present work, we investigated whether similar axons of vasomotor-type are generally present in the wall of pineal vessels, further, whether they reach the organ via the conarian nerves or via periarterial plexuses. In all species investigated, axons of perivasal nerve bundles were found to form terminal enlargements on the smooth muscle layer of pineal arterioles. The neuromuscular endings contain several synaptic and some granular vesicles. Axon terminals are also present around pineal veins. In serial sections, we found that the so-called conarian autonomic nerves reach the pineal organ alongside pineal veins draining into the great internal cerebral vein. Similar nerves present near arteries of the arachnoid enter the pineal meningeal capsule and septa by arterioles, both perivenous and periarterial nerves form terminals of vasomotor-type. The arteriomotor and venomotor regulation of the tone of the vessels of the pineal organ may serve the vascular support for circadian and circannual periodic changes in metabolic activity of the pineal tissue.

Animals↗
PubMed2005

Autonomic nerves terminating on microvessels in the pineal organs of various submammalian vertebrates.

In earlier works we have found that in the mammalian pineal organ, a part of autonomic nerves--generally thought to mediate light information from the retina--form vasomotor endings on smooth muscle cells of vessels. We supposed that they serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. In the present work, we investigated whether peripheral nerves present in the photoreceptive pineal organs of submammalians form similar terminals on microvessels. In the cyclostome, fish, amphibian, reptile and bird species investigated, autonomic nerves accompany vessels entering the arachnoidal capsule and interfollicular meningeal septa of the pineal organ. The autonomic nerves do not enter the pineal tissue proper but remain in the perivasal meningeal septa isolated by basal lamina. They are composed of unmyelinated and myelinated fibers and form terminals around arterioles, veins and capillaries. The terminals contain synaptic and granular vesicles. Comparing various vertebrates, more perivasal terminals were found in reptiles and birds than in the cyclostome, fish and amphibian pineal organs. Earlier, autonomic nerves of the pineal organs were predominantly investigated in connection with the innervation of pineal tissue. The perivasal terminals found in various submammalians show that a part of the pineal autonomic fibers are vasomotoric in nature, but the vasosensor function of some fibers cannot be excluded. We suppose that the vasomotor regulation of the pineal microvessels in the photosensory submamalian pineal--like in mammals--may serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. The higher number of perivasal terminals in reptiles and birds may correspond to the higher metabolic activity of the tissues in more differentiated species.

Amphibians↗
PubMed2006

Age-related changes in myocardial nerve and collagen networks of the auricle of the right atrium.

OBJECTIVE: The objective of this study was to analyse age-related changes in human myocardial nerve plexuses and collagen networks of the auricle of the right atrium in subjects in whom no cardiac diseases or pathology had been diagnosed. METHODS AND RESULTS: Morphometric analysis of acetylcholinesterase (AChE)-stained nerve plexuses and picrosirius-stained cardiac collagen networks from 17 persons of both genders aged 20-94 years was performed using video microscopy and a digital video camera. It was found that with age linear regression of nerve plexuses occurred.Atrial collagen content increases lifelong. CONCLUSION: Aging of human atrial myocardium is accompanied by a decrease of nerve plexuses and an increase in fibrosis.

Acetylcholinesterase↗