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PubMed1997

Trigeminal autonomic pathways involved in nociception-induced reflex cardiovascular responses.

Reflex cardiovascular responses elicited by noxious oro-facial stimulation are well known but the neural pathways that underlie trigeminal cardiovascular reflex reactions remain to be elucidated. In previous studies, we have shown that noxious electrical stimulation of the mandibular incisor in the anesthetized rat elicits increases in mean arterial blood pressure and heart rate (Allen, G.V., Barbrick, B. and Esser, M.J., Trigeminal parabrachial connections: possible pathway for nociception-induced cardiovascular reflex responses, Brain Res., 715 (1996) 125-135). In this study, microinjections of the presynaptic blocker, cobalt chloride, or the anesthetic agent, lidocaine, were made into selected brainstem sites to identify neural pathways that are involved in mediation of the reflex pressor responses. Ipsilateral and bilateral injections of chemical blocker into the dorsomedial spinal trigeminal nucleus, pars caudalis, lateral parabrachial nucleus and the rostral ventral lateral medulla/caudal A5 region attenuated the reflex cardiovascular response. Bilateral injections of cobalt chloride into the dorsomedial subnucleus caudalis resulted in 70-100% attenuation of the reflex pressor response. Bilateral injections of cobalt chloride and/or lidocaine into the lateral parabrachial nucleus or the rostral ventral lateral medulla/A5 region resulted in 43-57% and 44-100% attenuation of the reflex pressor response, respectively. There were no significant differences in the degree or duration of attenuation of the reflex pressor responses produced by cobalt chloride compared to that produced by lidocaine injections. The reflex pressor responses usually returned to baseline levels approximately 60 min following injection of the chemical blocker substance. The results indicate that noxious electrical stimulation of the mandibular incisor elicits a reflex increase in mean arterial blood pressure which is initially mediated in the dorsomedial spinal trigeminal nucleus, pars caudalis and is subsequently mediated in the lateral parabrachial nucleus and the rostral ventral lateral medulla/caudal A5 region.

Animals↗
PubMed2000

Integration of floral inductive signals in Arabidopsis.

Flowering of Arabidopsis is regulated by a daylength-dependent pathway that accelerates flowering in long days and a daylength-independent pathway that ensures flowering in the absence of inductive conditions. These pathways are genetically separable, as there are mutations that delay flowering in long but not short days. Conversely, mutations that block synthesis of the hormone gibberellin abolish flowering in short days, but have on their own only a minor effect in long days. A third pathway, the autonomous pathway, probably acts by modulating the other two pathways. Understanding where and how these pathways are integrated is a prerequisite for understanding why similar environmental or endogenous cues can elicit opposite flowering responses in different plants. In Arabidopsis, floral induction leads ultimately to the upregulation of floral meristem-identity genes such as LEAFY, indicating that floral inductive signals are integrated upstream of LEAFY Here we show that gibberellins activate the LEAFY promoter through cis elements that are different from those that are sufficient for the daylength response, demonstrating that the LEAFY promoter integrates environmental and endogenous signals controlling flowering time.

Arabidopsis↗
PubMed1992

Axonal and transsynaptic (transneuronal) spread of Herpesvirus simiae (B virus) in experimentally infected mice.

In order to study the pathogenesis of B virus infection of the nervous system, newborn and young mice were inoculated by four different routes: 1. Intramuscular (i.m.) in the forelimb; 2. I.m. in the hindlimb; 3. Subcutaneous (s.c.) in the abdominal wall; 4. Intraperitoneal (i.p.). Spread of virus was followed by immunohistochemical demonstration of viral antigen in tissue sections of the peripheral and central nervous system. Three distinct patterns emerged: 1. After i.m. limb inoculations, virus progressed along the ipsilateral dorsal column, the bilateral spinothalamic and bilateral spinoreticular systems and along central autonomic pathways. 2. After s.c. inoculation, the dorsal column was spared, otherwise the spread was similar to that following i.m. inoculations. 3. After i.p. inoculation, virus spread in the spinal cord bilaterally, mainly along spinothalamic and central autonomic pathways. The peripheral motoneurons were conspicuously spared, even in the i.m. inoculation mode. In the brain stem, B virus antigen appeared bilaterally, at multiple sites. In the cerebrum, virus infected cells appeared first in the thalamus, hypothalamus and the motor cortex. The mode of spread from spinal levels was mainly orthograde along the ascending systems (dorsal columns, spinothalamic, spinoreticular tracts), but also retrograde along descending systems (pyramidal tract, central autonomic pathways). Oligosynaptic systems transmitted virus more quickly than the polysynaptic ones. In the involvement of various neuronal systems in virus spread, a certain selectivity, sparing the peripheral motoneuron and the cerebellar systems, could be assessed.

Aging↗
PubMed1999

Distribution of NADPH-d and nNOS-IR in the thoracolumbar and sacrococcygeal spinal cord of the guinea pig.

The distribution of NADPH-d staining and neuronal nitric oxide synthase (nNOS)-immunoreactivity in the spinal cord of the guinea pig was studied to evaluate the potential role of nitric oxide in lumbosacral afferent and spinal autonomic pathways and to compare the distribution of these two markers to that observed in other species. NADPH-d staining and nNOS-immunoreactivity were present in neurons and fibers in the superficial dorsal horn, dorsal commissure and in neurons around the central canal in all levels of the spinal cord examined. Sympathetic preganglionic neurons in the thoracic and rostral lumbar segments identified by choline acetyl transferase (ChAT) immunoreactivity exhibited prominent NADPH-d staining and nNOS-immunoreactivity; whereas the ChAT-immunoreactive parasympathetic preganglionic neurons in the sacral segments were not stained. The most prominent NADPH-d staining in the sacral segments occurred in fibers extending from Lissauer's tract through laminae I along the lateral edge of the dorsal horn to the region of the sacral parasympathetic nucleus (lateral collateral pathway of Lissauer). These fibers were prominent in the S1-S3 segments but not in adjacent (L5-L7 and Cx1) or thoracolumbar segments. These NADPH-d fibers were, for the most part, not nNOS-immunoreactive, but did overlap with a prominent fiber bundle containing vasoactive intestinal polypeptide immunoreactivity in the sacral spinal cord. These results indicate that nitric oxide may function as a transmitter in thoracolumbar sympathetic preganglionic neurons, but not in sacral parasympathetic preganglionic neurons. Although the functional significance of the NADPH-d positive, nNOS-negative fiber bundle on the lateral edge of the sacral dorsal horn remains to be determined, this fiber tract may represent, in part, visceral afferent projections to the sacral parasympathetic nucleus.

Afferent Pathways↗
PubMed2000

Induction of specific phosphodiesterase isoforms by constitutive activation of the cAMP pathway in autonomous thyroid adenomas.

Thyrocytes largely depend on cAMP signaling for replication and differentiation. This pathway may be constitutively activated by mutations of the TSH receptor (TSHR) and Gsalpha in autonomous thyroid adenomas (ATAs). Because steady state cAMP results from production by adenylyl cyclase and degradation by phosphodiesterases (PDEs), we evaluated PDE activity and expression in ATAs with wild-type and mutant TSHR and Gsalpha. Activating mutations of TSHR and Gsalpha were identified in 7 and 1 of 18 ATAs, respectively. No difference was observed in the cAMP content in ATAs with or without activating mutants. In the surrounding normal thyroid tissue (NTs), PDE activity was 80% isobutylmethylxanthine sensitive, with the major contribution by PDE1 and a minor contribution by PDE4. No differences were observed in PDE activities between NTs and ATAs with wild-type TSHR and Gsalpha. In contrast, in the presence of mutant TSHRs or Gsalpha, total PDE activity was higher. This increase was primarily due to PDE4 induction (917 +/- 116% over NTs), associated with a minor PDE1 increase only in ATAs with mutant TSHR. By RT-PCR, increments of PDE4D and 4C messenger ribonucleic acids were found in the ATAs with mutant TSHR or Gsalpha, whereas messenger ribonucleic acids encoding other cAMP-specific PDEs were not significantly increased. This study provides a characterization of the PDEs expressed in human thyroid and demonstrates a dramatic PDE4 induction in the ATAs bearing mutant TSHR or Gsalpha genes. The increase in cAMP-degrading activity may represent a marker of constitutive adenylyl cyclase activation and constitutes an intracellular feedback mechanism with significant impact on the phenotypic expression of the activating mutations.

Adenoma↗
PubMed1996

[Electrophysiologic diagnosis in erectile dysfunction].

So far, electrophysiological examinations have rarely been used in the diagnosis of erectile dysfunction (ED) mainly because the methods available only allow somatic neuron pathways to be examined whose relevance for the mainly autonomically controlled crection is evaluated differently. At present, impaired penile nerve supply as the possible cause of ED can only be evaluated through neurophysiological screening of the somatic and autonomic pathways of the pelvic floor, and not just by one simple method. Diagnosing ED should include testing of motoric efferences through electroneurography of the pudendal nerve and electromyography of the external anal sphincter and the urethral sphincter. Sensitive afference is tested with somatosensory evoked potentials of the pudendal nerve. New methods that are available for the examination of autonomic pathways are the penile sympathetic skin response and the EMG of the corpus cavernosum. Together with the other electrophysiological examinations, they allow neurogenic causes to be determined and differentiate not only between central and peripheric lesions, but also between acute and chronic changes. Prognosis can also be estimated. A crucial diagnostic deficit is the fact that it is still not possible to test the parasympathetic system directly.

Autonomic Nervous System↗
PubMed1999

The early-flowering mutant efs is involved in the autonomous promotion pathway of Arabidopsis thaliana.

The transition to flowering is a crucial moment in a plant's life cycle of which the mechanism has only been partly revealed. In a screen for early flowering, after mutagenesis of the late-flowering fwa mutant of Arabidopsis thaliana, the early flowering in short days (efs) mutant was identified. Under long-day light conditions, the recessive monogenic efs mutant flowers at the same time as wild type but, under short-day conditions, the mutant flowers much earlier. In addition to its early-flowering phenotype, efs has several pleiotropic effects such as a reduction in plant size, fertility and apical dominance. Double mutant analysis with several late-flowering mutants from the autonomous promotion (fca and fve) and the photoperiod promotion (co, fwa and gi) pathways of flowering showed that efs reduces the flowering time of all these mutants. However, efs is completely epistatic to fca and fve but additive to co, fwa and gi, indicating that EFS is an inhibitor of flowering specifically involved in the autonomous promotion pathway. A vernalisation treatment does not further reduce the flowering time of the efs mutant, suggesting that vernalisation promotes flowering through EFS. By comparing the length of the juvenile and adult phases of vegetative growth for wild-type, efs and the double mutant plants, it is apparent that efs mainly reduces the length of the adult phase.

Arabidopsis↗
PubMed1988

Calcitonin gene-related peptide containing autonomic efferent pathways to the pelvic ganglia of the rat.

Indirect immunofluorescence method was employed to investigate the involvement of calcitonin gene-related peptide (CGRP) in the autonomic efferent innervations of the pelvic visceral organs of the rat. Cells labeled with Fast blue (FB) injected into the pelvic ganglia were observed in the sacral parasympathetic nucleus; about 30% of these neurons showed CGRP-like immunoreactivity. These CGRP-like immunoreactive neurons were located in the dorsomedial part of the sacral parasympathetic nucleus, extending their dendrites mediolaterally. FB-labeled cells were also found in the upper lumbar level (L1, L2) of the spinal cord. Some of these neurons also showed CGRP-like immunoreactivity. CGRP-like immunoreactive varicose fibers were seen in the pelvic ganglia surrounding individual ganglion cells. Considerable amount of these fibers were not affected by sensory deafferentation, so they probably originated from autonomic efferent neurons.

Animals↗
PubMedDate not supplied

Connections between the vestibular nuclei and brain stem regions that mediate autonomic function in the rat.

Clinical observations have long indicated a vestibular influence on autonomic function. Neuroanatomical studies in the rabbit and in the cat have identified descending vestibulo-autonomic pathways from the caudal portion of the medial vestibular nucleus and the inferior vestibular nucleus to the dorsal motor nucleus of the vagus nerve, the nucleus of the solitary tract, and some brain stem medullary sympathetic regions. This study describes vestibulo-autonomic pathways in rats. One group of Long-Evans rats received injections of tetramethylrhodamine dextran into the caudal aspect of the vestibular nuclear complex. Anterogradely labeled descending fibers were traced bilaterally to lateral, ventrolateral, and intermediate subnuclei of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. A small number of axons also projected bilaterally to the nucleus ambiguus, the ventrolateral medulla, and the nucleus raphe magnus. Finally, anterogradely labeled ascending fibers were traced from the caudal medial vestibular nucleus and the inferior vestibular nucleus to the medial, lateral, ventrolateral, and Kolliker-Fuse regions of parabrachial nucleus. A second group of rats received iontophoretic injections of Fluoro-gold into the nucleus of the solitary tract to identify the cells of origin of the vestibulo-solitary projection. Similar to findings in the rabbit (Balaban and Beryozkin, 1994), retrogradely labeled cells were observed in the caudal medial vestibular nucleus and the inferior vestibular nucleus. These findings are consistent with the hypothesis that a common pattern of vestibular nuclear projections to autonomic regions is shared by rabbits, cats, and rats.

Animals↗
PubMed1999

Effect of radiofrequency catheter ablation of accessory pathways on autonomic tone in children.

BACKGROUND: Radiofrequency catheter ablation is standard treatment for children with re-entrant supraventricular tachycardias. Autonomic changes have been noted after such ablation for atrioventricular nodal re-entry tachycardia, but not as well documented with atrioventricular re-entry over an accessory pathway. METHODS AND RESULTS: In 10 normal paediatric volunteers and 12 children referred for electrophysiologic testing and radiofrequency ablation of supraventricular tachycardia, non-invasive autonomic function tests and tilt-table testing were performed, and the variability in 24-h heart rate was analysed. Patients with supraventricular tachycardia underwent these tests both 24-72 h before and 24 h after ablation. Patients with tachycardia underwent additional autonomic testing to assess the sensitivity of baroreceptors and the intrinsic heart rate with autonomic blockade immediately before and after ablation. One non-invasive autonomic function test, namely handgrip, demonstrated significant differences (p < 0.05) in diastolic blood pressure before and after ablation, though these values did not differ from controls. Significant decreases were noted in two indexes of the variability of heart rate before and after ablation (p < 0.05). Certain tilt test variables also demonstrated significant differences between controls and those with tachycardia subsequent to ablation. Intracardiac testing demonstrated changes (p < 0.05) in sinus cycle lengths, effective refractory periods and/or blood pressures at baseline and during testing of the sensitivity of baroreceptors before and after ablation. These changes were consistent with increased sympathetic or decreased parasympathetic tone. With autonomic blockade, these differences were abolished. CONCLUSIONS: Catheter ablation of accessory pathways in children was associated with changes consistent with increased sympathetic or decreased parasympathetic tone. These autonomic changes persisted 24 h after the ablation procedure.

Adolescent↗
PubMedDate not supplied

The role of neuropeptides in the sacral autonomic reflex pathways of the cat.

Immunohistochemical and pharmacological studies were conducted to examine the origin and function of peptidergic nerves in the sacral autonomic system of the cat. Leucine-enkephalin (L-Enk) immunoreactivity was identified in nerve terminals in peripheral ganglia on the surface of the urinary bladder and in the parasympathetic nucleus in the sacral spinal cord. In colchicine-treated animals L-Enk was also detected in sacral preganglionic neurons (sPGN) identified by retrograde transport of a fluorescent dye. L-Enk terminals in bladder ganglia are believed to arise from sPGN since the terminals were eliminated by transection of the sacral ventral roots. Pharmacological studies indicated that exogenous as well as endogenously released enkephalins have an inhibitory action at both ganglionic and spinal sites in the sacral outflow to the urinary bladder. Peptides were also associated with afferents nerves in the sacral autonomic system. The distribution of substance P, VIP and cholecystokinin in the sacral dorsal horn paralleled the distribution of visceral afferent projections as demonstrated with HRP techniques. Dye labeling combined with immunohistochemistry revealed that some dorsal root ganglion cells projecting to the pelvic viscera contain substance P or VIP.

Animals↗
PubMed1983

Hereditary neuropathy with upper motor-neuron, visual pathway, and autonomic disorders.

A 42-year-old man had progressive distal weakness and muscle atrophy, stocking-type sensory loss, upper motor-neuron and visual pathway lesions, and dysautonomia. Electrodiagnostic tests revealed a generalized sensorimotor peripheral neuropathy that largely involved axons. Low recumbent and upright norepinephrine levels implied a peripheral autonomic defect. Sural nerve biopsy showed mild abnormalities of medium and small size fibers. The patient's mother and two brothers were also affected. Other causes of peripheral motor, sensory, and autonomic failure were eliminated. This kinship does not fit any generally accepted classification of hereditary neuropathies.

Adult↗
PubMed1975

Retrograde axonal transport of horseradish peroxidase in peripheral autonomic nerves.

An exogeneous marker protein, horseradish peroxidase (HRP) was used to race peripheral autonomic pathways in adult guinea pigs and cats. Small doses of HRP were injected into various organs and after a brief survival period, HRP activity appeared in the perikarya of autonomic neurons that supplied each injection site. After injection of HRP into the anterior chamber of the eye, reaction product was detected in the postganglionic sympathetic neurons of the superior cervical sympathetic ganglion. In another experiment, HRP reaction product was found in the cell bodies of the preganglionic sympathetic neurons that supply the adrenal medulla. These were located in the lateral gray column of the spinal cord at T6 and T7 segmental levels. Reaction product appeared in intramural postganglionic parasympathetic neurons close to an injection site in the wall of the urinary bladder and in a similiar situation in Meissner's ganglia of the ileum. Following injection into the walls of the stomach and ileum, HRP labelled cells were detected in the nodose ganglion of the vagus and in preganglionic parasympathetic neurons in the dorsal motor nucleus of this nerve. After injection into the subepicardial tissue of the heart, reaction product appeared in the stellate ganglion and also in an upper thoracic dorsal root ganglion. These data suggest that HRP is taken up by peripheral autonomic nerves of all types, and then undergoes rapid retrograde axonal transport to the perikaryon. It appears, therefore, that HRP may be useful in tracing both motor and sensory peripheral autonomic pathways.

Adrenal Medulla↗
PubMed1984

Fastigial nucleus projections to the brain stem in beagles: pathways for autonomic regulation.

Efferent connections from a portion of the cerebellar fastigial nucleus were investigated using autoradiography. Bipolar stimulating electrodes were placed in the fastigial nucleus of anesthetized beagles and the area that produced increases in blood pressure and heart rate was localized. A mixture of [3H]leucine and [3H]proline (4:1) was injected into the area and autoradiograms of transported material were prepared. Injections filled the rostral and various parts of the caudal fastigial nucleus. Labeled axons reached the brain stem via two routes, the ipsilateral juxtarestiform body and the contralateral uncinate fasciculus. Ventral portions of the lateral vestibular nucleus were labeled bilaterally, projections to the inferior vestibular and medial vestibular nuclei are contralateral. Nucleus tractus solitarius was heavily labeled on the side opposite the injection. The contralateral medial reticular formation contained many labeled terminals and axons. Label was found in the nucleus reticularis ventralis, lateral reticular nucleus, nucleus gigantocellularis, nucleus pontis caudalis and the paramedian reticular nucleus. No terminal labeling was found in nucleus parvocellularis or nucleus ambiguous. Stimulation of the rostral fastigial nucleus produces increases in blood pressure and heart rate by generalized sympathoexcitation. Many cell groups which facilitate the activity of preganglionic sympathetic neurons do not receive direct fastigial input. It is suggested that that sympathoexcitation resulting from stimulation of the fastigial nucleus occurs through multisynaptic connections in the brain stem.

Animals↗