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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↗

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↗

Effects of restraint stress and spontaneous hypertension on neuropeptide Y neurones in the brainstem and arcuate nucleus.

Neuropeptide Y (NPY) is found in autonomic neurones and participates in regulation of autonomic functions. To investigate the role of NPY in the stress response in normo- and hypertensive rats, activation of brainstem and arcuate nucleus (ARC) NPY neurones and levels of NPY mRNA in the ARC were measured in response to restraint stress in adult spontaneously hypertensive rats (SHRs) and two strains of normotensive rats. Controls from each strain were not restrained. Sections of the brain were prepared for Fos immunohistochemistry and NPY in-situ hybridization to identify activated NPY neurones in the nucleus of the tractus solitarii (NTS), ventrolateral medulla (VLM), and ARC. NPY mRNA levels were quantified in the ARC. In the NTS and VLM of restrained rats, approximately 33% and 75%, respectively, of NPY neurones were activated. No differences among strains were found. In the ARC, about 36% of neurones activated by restraint contained NPY mRNA with no differences found among strains. In unrestrained rats, NPY mRNA levels were significantly elevated in SHRs compared to the normotensive rats. Restraint led to significant decreases in mRNA levels in all strains and mRNA levels among strains were no longer different from one another. These data show that NPY likely participates as a neurotransmitter in the autonomic pathways utilized during stress and originating in the NTS, VLM, and ARC. On the other hand, the decreased gene expression of NPY in the ARC in response to restraint stress argues against a role for activation of autonomic pathways or the hypothalamo-pituitary-adrenal (HPA) axis by NPY from the ARC of stressed rats. The elevated NPY gene expression in resting SHRs compared to normotensive rats is abrogated after restraint, suggesting that this gene is differentially regulated in SHRs compared to normotensive rats.

Animals↗

Interleukin 2 pathway is autonomously activated in human T11+3-4-6-8- thymocytes.

Mitogenic membrane ligands have been shown to activate interleukin 2 (IL2) production only in mature T cells, IL2 constitutive secretion having not yet been demonstrated. Here we have isolated a population of T11+3-4-6-8- human thymocytes and CD7+/T11-3-4-6-8- prothymocytes which produce and consume IL2 upon phytohemagglutinin triggering. Interestingly, their proliferation in the absence of any exogenous stimulating agent was related to an autonomous use of the IL2 system (IL2 secretion and binding to its specific receptor, whose constitutive, functional expression in human early thymocytes was recently shown). The internal activation of this system before T cell receptor acquisition stresses the relevance of the understanding of the alternative activation pathway(s) in T cell development. These findings, together with the demonstration of IL2-promoted differentiation of human early thymocytes into mature T cells, suggest that IL2 may also be a growth and differentiation factor acting specifically early in T cell development.

Antigens, Differentiation, T-Lymphocyte↗

Neurally mediated increase in mitosis and DNA of rat parotid with increase in bulk of diet.

A transient burst of mitosis was induced in rat parotid gland 2 days after change from a diet of solid chow only to one consisting of 50% inert cellulose and 50% solid chow (bulk diet). Mitosis was thus induced when glandular activity was changed from normal levels (solid chow) to levels greater than normal (bulk diet). Elimination of either autonomic pathway inhibited the mitotic response, but elimination of the parasympathetic had the greater inhibitory influence. The burst of mitosis induced by bulk diet was followed by increases in total DNA (16%), RNA (24%) and weight (27%) of the gland 2 wk after the dietary change. These changes did not occur when both autonomic pathways were, or only the parasympathetic was, removed immediately prior to the dietary change. Effects of sympathectomy were less pronounced. The parasympathetic innervation has the principal role in regulation of mitosis, cell number and size, and nucleic acid content when glandular activity is increased above normal by physiological means.

Animals↗

Autonomous neurobiological pathways to late-life major depressive disorder: clinical and pathophysiological implications.

The objective of our study was to elucidate distinct paths to depression in a model that incorporates age, measures of medical comorbidity, neuroanatomical compromise, and cognitive status in a sample of patients with late-life major depressive disorder (MDD) and nondepressed controls. Our study was cross-sectional in nature and utilized magnetic resonance imaging (MRI) estimates of brain and high-intensity lesion volumes together with clinical indices of cerebrovascular and nonvascular medical comorbidity. Neuroanatomic and clinical measures were incorporated into a structural covariance model in order to test pathways to MDD. Our data indicate that there are two paths to MDD; one path is represented by vascular and nonvascular medical comorbidity that contribute to high-intensity lesions that lead to depression. Smaller brain volumes represent a distinct path to the mood disorder. Age influences depression by increasing atrophy and overall medical comorbidity but has no direct impact on MDD. These findings demonstrate that there are distinct biological substrates to the neuroanatomical changes captured on MRI. These observations further suggest that neurobiological mechanisms acting in parallel may compromise brain structure/function, thereby predisposing individuals to clinical brain disorders such as depression.

Affect↗

Diarrhea- and constipation-predominant IBS patients differ in postprandial autonomic and cortisol responses.

OBJECTIVE: As the primary link between brain and gut, autonomic and endocrine dysfunction may play a role in the pathophysiology of the irritable bowel syndrome (IBS). The aim of this study was to assess autonomic, endocrine, and symptomatic responses to food intake in diarrhea-predominant and constipation-predominant IBS patients, compared to normals. METHODS: Twelve women with diarrhea-predominant or alternating IBS (IBS-D), 12 women with constipation predominant IBS (IBS-C), and 20 healthy women participated. GI symptoms, saliva cortisol concentration, heart rate, and heart rate variability were assessed at baseline and after a meal. Spectral analysis of heart rate variability was used as a measure of the sympathovagal regulation of the heart rate. RESULTS: Both groups of IBS patients showed a significant postprandial increase in GI symptoms. IBS-D showed a significant increase in the low frequency/high frequency band ratio and a decrease in the high frequency band power during the first postmeal period, which was significantly different, not only from controls, but also from IBS-C. IBS-D also showed a significant postprandial increase in cortisol, which was not evident in controls or IBS-C. There was a significant correlation between the vagal response and the postprandial increase in GI symptoms in IBS-D (r = 0.6, p < 0.05). CONCLUSIONS: These findings support the notion that the IBS symptom groups are characterized by different physiological responses to visceral stimuli, and point to a role of autonomic pathways in IBS symptomatology.

Adult↗

An epinephrine-containing pathway in avian spinal cord: development and localization.

We have studied the uptake mechanism, biochemistry and autoradiographic localization of a descending epinephrine-containing pathway in the chick spinal cord. This epinephrine (E) projection has a developmental timetable (appears at 14 days in ovo) that is different from those of the serotonin (5-HT) and norepinephrine (NE) projections which appear at 8 and 12 days respectively. E possesses its own uptake mechanism with different pharmacological specificities from those of the NE and 5-HT uptake mechanisms. Phenylethanolamine-N-methyltransferase (PNMT), the enzyme that converts NE to E, is present in the cord at 14 days in ovo which is the same time that the uptake mechanism is detectable. Transection of the spinal cord at upper thoracic levels almost completely eliminates the uptake mechanism and PNMT activity below the transection, indicating a supraspinal origin of this pathway. E can first be detected fluorimetrically at 12 days in ovo but at this age E appears not to be of supraspinal origin since transmission at 5 days in ovo does not deplete the spinal cord of E. However, transection of the spinal cord at 3 days post-hatching does markedly reduce the E content by 12 days. Autoradiographic analysis after uptake with [3H]E shows a circumscribed localization of the uptake of E to the neuropil of the preganglionic sympathetic nucleus (nucleus of Terni). These observations demonstrate the presence of a separate descending epinephrine-containing projection in the avian spinal cord which terminates predominantly on preganglionic sympathetic neurons. This pathway may be the major central autonomic pathway in the avian spinal cord.

Aging↗

Reflex bronchial vasodilation in dogs evoked by injection of a small volume of water into a bronchus.

Injection of water into a lobar bronchus stimulates airway C-fibers and rapidly adapting receptors and evokes airway defense reflexes. To determine whether this stimulus also evokes a reflex increase in bronchial blood flow (Qbr), we injected 1-2 ml of water into a lobar bronchus in anesthetized dogs. Injection decreased arterial pressure but increased Qbr from 9 +/- 1 to 21 +/- 3 ml/min. The increase had a latency of 6-8 s and reached a peak after approximately 20 s; Qbr returned to control after 60-90 s. Airway mucosal blood flow, measured by colored microspheres, increased in proportion to Qbr. In contrast, flow in an adjacent intercostal artery that did not supply the airway decreased slightly. Injection of isosmotic saline had little effect. In 13 of 16 dogs, the water-induced increase in Qbr was abolished by cutting or cooling the cervical vagus nerves and hence was entirely dependent on centrally mediated vagal pathways. When the vagus nerves were intact, about one-third of the vasodilator response remained after pharmacological blockade of muscarinic and adrenergic receptors. We conclude that in dogs the defense response to water in the lower airways includes a large increase in Qbr that is partly due to activation of nonadrenergic noncholinergic autonomic pathways.

Animals↗

Localization of NADPH diaphorase in the lumbosacral spinal cord and dorsal root ganglia of the cat.

The distribution of NADPH-d activity in the spinal cord and dorsal root ganglia of the cat was studied to evaluate the role of nitric oxide in lumbosacral afferent and spinal autonomic pathways. At all levels of the spinal cord NADPH-d staining was present in neurons and fibers in the superficial dorsal horn and in neurons around the central canal and in the dorsal commissure. In addition, the sympathetic autonomic nucleus in the rostral lumbar segments exhibited prominent NADPH-d cellular staining whereas the parasympathetic nucleus in the sacral segments was not well stained. The most prominent NADPH-d activity in the sacral segments occurred in fibers extending from Lissauer's tract through laminae I along the lateral edge of the dorsal horn to lamina V and the region of the sacral parasympathetic nucleus. These fibers were very similar to VIP-containing and pelvic nerve afferent projections in the same region. They were prominent in the S1-S3 segments but not in adjacent segments (L6-L7 and Cx1) or in thoracolumbar and cervical segments. NADPH-d activity and VIP immunoreactivity in Lissauer's tract and the lateral dorsal horn were eliminated or greatly reduced after dorsal-ventral rhizotomy (S1-S3), indicating the fibers represent primary afferent projections. A population of small diameter afferent neurons in the L7-S2 dorsal root ganglia were intensely stained for NADPH-d. The functional significance of the NADPH-d histochemical stain remains to be determined; however, if NADPH-d is nitric oxide synthase then this would suggest that nitric oxide may function as a transmitter in thoracolumbar sympathetic preganglionic efferent pathways and in sacral parasympathetic afferent pathways in the cat.

Afferent Pathways↗

The pha-4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans.

In the 4-cell Caenorhabditis elegans embryo, two blastomeres are destined to generate pharyngeal cells, each by a distinct developmental strategy: one pathway is inductive, while the other is autonomous. Here, we identify the pha-4 locus. In animals lacking pha-4 activity, an early step in pharyngeal organogenesis is blocked: no pharyngeal primordium is formed and differentiated pharyngeal cells are absent. Most other tissues are generated normally in pha-4 mutants, including cells related to pharyngeal cells by cell lineage and position. Thus, pha-4 activity is required to form the pharyngeal primordium. We propose that pha-4 marks a convergence of the inductive and autonomous pathways of pharyngeal development and suggest that establishment of pharyngeal organ identity is a crucial step for pharyngeal organogenesis.

Animals↗

Neurophysiological evaluation of sexual dysfunction in familial amyloidotic polyneuropathy--Portuguese type.

Familial amyloidotic polyneuropathy (FAP)--Portuguese type, is an autosomal dominant polyneuropathy related with an abnormal transthyrretin (TTR Met 30). In males, the first complaint can be sexual dysfunction. Fifteen FAP patients, mean age 37 +/- 7.7 years, mean disease duration 5.2 +/- 2.2 years, all males, complaining of sexual dysfunction were studied with pudendal evoked potentials (PEP), bulbocavernous reflex (BCR) and sympathetic skin response (SSR). PEP and BCR reflect the central somatosensory pathways and sacral arch functioning; SSR relates with autonomic pathways. The aims of this study were: to correlate clinical and EMG scores with somatic and autonomic fibres involvement; to evaluate the timing of somatic and autonomic nerves lesion in disease evolution. Results showed: that PEP and BCR abnormalities have a statistically significant correlation with clinical and EMG scores; abnormal SSR in the plant precede other clinical or EMG abnormalities in the present study.

Adult↗

Autonomic stimulation.

Therapeutic stimulation of the autonomic nervous system has been limited by lack of qualitative or quantitative evaluation of autonomic mechanisms. This article provides an historical review of knowledge about autonomic pathways and critical evaluation of available tests of autonomic function. Recent developments in evaluation of autonomic dysfunction and improvement in techniques of neurostimulation have facilitated the development of a number of clinically useful treatments for bladder control, sexual problems, peripheral vascular disease, angina pectoris, and seizure disorders. Future therapeutic measures may allow specific control of hypertension, pain, cardiac arrhythmias, trophic disorders and balance.

Autonomic Nervous System↗

Autonomic dysreflexia: pharmacological management of hypertensive crises in spinal cord injured patients.

Interruption of autonomic pathways by spinal cord injury (SCI) causes dysfunctional autonomic dysreflexia (AD), which was first described in 1917, still remains unrecognized by those in the medical profession not involved in SCI care. Autonomic dysreflexia is a syndrome generally manifest by cardiovascular symptoms and characterized by paroxysmal hypertension. These symptoms appear in patients with spinal cord injury above the sympathetic outflow from the spinal cord (T6). Since patients with high level SCI are usually hypotensive, the high blood pressures that develop during AD represent pressure changes of a magnitude that can cause cerebrovascular accidents and death of the subject. We discuss the therapeutic interventions that abate and curtail the symptoms and prevent the catastrophic sequelae of autonomic dysreflexia.

Autonomic Nervous System Diseases↗

Right ventricular infarction causes heterogeneous autonomic denervation of the viable peri-infarct area.

BACKGROUND: Because efferent autonomic pathways to the right ventricle (RV) differ from the efferent autonomic projections to the left ventricle (LV), we assessed the effects of RV infarction on this innervation. METHODS AND RESULTS: We measured the ventricular effective refractory period (ERP) shortening in response to bilateral ansae subclaviae stimulation and ERP lengthening induced by bilateral vagal stimulation as markers of autonomic innervation before and after RV myocardial infarction (RVMI) produced by coronary ligation (n=28 dogs) or intracoronary latex injection (n=18 dogs) into a marginal branch of the right coronary artery in open-chest anesthetized dogs. In each dog, ERPs measured in viable peri-infarct area at two RV outflow tract (RVOT) sites and two septal and four lateral sites at the RV free wall after RVMI showed reduced or absent ERP shortening during bilateral ansae subclaviae stimulation laterally, septally, and at RVOT sites 3 hours after RVMI. ERP shortening in response to infused norepinephrine was still present. Bilateral vagal stimulation during background norepinephrine infusion (0.10 to 0.25 microg/kg per minute) lengthened the ERP at all test sites before latex injection. After transmural RVMI, vagally induced ERP prolongation was attenuated or lost at lateral, septal, and RVOT test sites. CONCLUSIONS: RVMI causes sympathetic and vagal denervation at viable sites at the RVOT, lateral, and, to a lesser extent, septal sides of the viable peri-infarct area. Autonomic denervation in the RVOT might contribute to the development of ventricular tachyarrhythmias after the acute stage of myocardial infarction involving the RV.

Animals↗

Electromyography of cavernous smooth muscle during flaccidity: evaluation of technique and normal values.

Objective evaluation of the penile innervation in impotent patients is mostly restricted to examination of the somatic pudendal pathways. These tests provide little information on the pelvic-cavernous autonomic innervation of the corporeal bodies. Electromyography of the flaccid penile smooth muscle is a reproducible and non-invasive method of evaluating these autonomic pathways and the status of intrinsic smooth muscle. Examination techniques and normal values have been studied in 15 young and potent volunteers. Recordings in 13 patients with neuropathology and 57 impotent patients are discussed.

Adult↗

Central neural regulation of penile erection.

Penile erection is caused by a change of the activity of efferent autonomic pathways to the erectile tissues and of somatic pathways to the perineal striated muscles. The spinal cord contains the cell bodies of autonomic and somatic motoneurons that innervate the peripheral targets. The sympathetic outflow is mainly antierectile, the sacral parasympathetic outflow is proerectile, and the pudendal outflow, through contraction of the perineal striated muscles, enhances an erection already present. The shift from flaccidity to erection suggests relations among these neuronal populations in response to a variety of informations. Spinal neurons controlling erection are activated by information from peripheral and supraspinal origin. Both peripheral and supraspinal information is capable of eliciting erection, or modulating or inhibiting an erection already present. One can hypothesize a spinal network consisting of primary afferents from the genitals, spinal interneurons and sympathetic, parasympathetic and somatic nuclei. This system is capable of integrating information from the periphery and eliciting reflexive erections. The same spinal network, eventually including different populations of spinal interneurons, would be the recipient of supraspinal information. Premotor neurons that project directly onto spinal sympathetic, parasympathetic or somatic motoneurons, are present in the medulla, pons and diencephalon. Several of these premotor neurons may in turn be activated by sensory information from the genitals. Aminergic and peptidergic descending pathways in the vicinity of spinal neurons, exert complex effects on the spinal network that control penile erection. This is caused by the potential interaction of a great variety of receptors and receptor subtypes present in the spinal cord. Brainstem and hypothalamic nuclei (among the latter, the paraventricular nucleus and the medial preoptic area) may not necessarily reach spinal neurons directly. However they are prone to regulate penile erection in more integrated and coordinated responses of the body, such as those occurring during sexual behavior. Finally, the central and spinal role of regulatory peptides (oxytocin, melanocortins, endorphins) has only recently been elucidated.

Animals↗