Neurogenesis in the adult peripheral nervous system

Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence ofinsult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.     

Expression of NGF receptor in the developing and adult primate central nervous system

Monoclonal antibodies against human NGF receptor have been used for immunocytochemical localization of NGF receptors in the CNS of macaques and baboons at various stages of development. In the adult, neurons in most brain regions are devoid of detectable NGF receptors. However, abundant NGF receptor immunoreactivity is present on a population of neurons in basal forebrain, which, on the basis of appearance and pattern of distribution, probably correspond, at least in part, to magnocellular cholinergic neurons of this region. NGF receptors were also associated with the vasculature in most brain regions. NGF receptor immunoreactivity is present on Mueller glia of neural retina. In macaque fetuses, approximately 1 month prenatally, retinal Mueller glia possess lower levels of receptor, while higher levels of receptor are present in the retinal nerve fiber layer. In fetal cerebellum, abundant receptor immunoreactivity is present on Purkinje cells, granule cells of the premigratory zone of the external granule layer, and neurons of the deep nuclei. Immunoreactivity decreases with subsequent development and is absent in the adult. In cerebellum, levels of NGF receptor assayed by affinity crosslinking to radioiodinated NGF, and levels of NGF receptor mRNA assayed by Northern blot analysis decrease dramatically during the last month of fetal life.     

Analysis of myelin proteins in sympathetic peripheral nerve of adult rats

Biochemical analyses of myelin proteins in rat sympathetic peripheral nerve were correlated with morphological observations. Myelin proteins in superior cervical ganglia (SCG) and the paravertebral (thoraco-lumbar) chain of ganglia were quantitated by immunoassays and examined qualitatively by Western blotting. The results were compared to those obtained on sciatic nerves from the same animals. In rats aged one year, the concentrations of PO glycoprotein and myelin basic protein (MBP) in SCG were about 1% of those in sciatic nerve, consistent with the relatively low numbers of myelinated fibers in sympathetic nerve. The relative concentration of myelin-associated glycoprotein (MAG) was higher, being 6.7% of that in sciatic nerve. The latter finding is probably due to the greater proportion of MAG-containing membranes (periaxonal, paranodal, and Schmitt-Lanterman incisures) in myelinated fibers of the SCG, in which the internodes are both short and thinly myelinated. The proportion of the 21 kDa, 18 kDa and 17 kDa forms of MBP relative to the 14 kDa form was much higher in SCG than in sciatic nerve, probably reflecting the fact that myelin formation continues actively during adult life in the ganglia, whereas the deposition of myelin is complete at a much earlier age in somatic nerves. The levels of myelin proteins were 2- to 3-fold higher in the paravertebral chain ganglia. These studies indicate that quantitation of myelin proteins in sparsely myelinated sympathetic nerve tissue is feasible and provide a baseline for further studies on the control of myelination in sympathetic nerve during adult life.     

Connections of Barrington's nucleus to the sympathetic nervous system in rats

Barrington's nucleus (BN) has been considered a pontine center related exclusively to the control of pelvic parasympathetic activity. The present study demonstrates an anatomical linkage between BN and autonomic outflow to visceral targets innervated exclusively by the sympathetic division of the autonomic nervous system. Temporal analysis of infection after injection of pseudorabies virus (PRV), a retrograde transynaptic tracer, into two sympathetically innervated organs, the spleen and the kidney, revealed the presence of infected neurons in BN at early post-inoculation survival intervals. Immunohistochemical localization of PRV after spleen injections showed that a small subpopulation of BN neurons became labeled in a time frame coincident with the appearance of infected neurons in other brain regions known to project to sympathetic preganglionic neurons (SPNs) in the thoracic spinal cord; a larger number of infected neurons appeared in BN at intermediate intervals after PRV injections into the spleen or kidney. Coinjection of the retrograde tracer Fluoro-Gold i.p. and PRV into the spleen demonstrated that parasympathetic preganglionic neurons in the caudal medulla or lumbo-sacral spinal cord were not infected, indicating that infected BN neurons were not infected via a parasympathetic route. Thus, BN neurons become infected after PRV injections into the spleen or kidney either directly through BN projections to SPNs, or secondarily via BN projections to infected pre-preganglionic neurons. These results demonstrate an anatomical linkage, either direct or indirect, between BN and sympathetic activity. Because BN receives numerous inputs from diverse brain regions, the relation of BN with both branches of the autonomic nervous system suggests that this nucleus might play a role in the integration of supraspinal inputs relevant to the central coordination of sympathetic and parasympathetic activity.     

Expression of HGF and cMet in the peripheral nervous system of adult rats following sciatic nerve injury

Hepatocyte growth factor (HGF) exhibits neurotrophic properties on different types of neuron, including motor, sensory and parasympathetic neurons. We demonstrate that sciatic nerve ligation induces an increase of the HGF receptor, c-met, mRNA in the distal segment of the sciatic nerve to the ligation site and a delayed elevation in the proximal segment. Immunohistochemical analysis revealed co-localization of cMet and GFAP and indicates that Schwann cells express cMet in the sciatic nerve after injury. HGF mRNA was detected in the spinal cord and DRG, and nerve injury did not alter the expression. These data demonstrate that the expression of HGF and cMet in the peripheral nervous system shows the unique pattern of regulation following nerve injury.     

A model for investigating the effect of drugs on the peripheral sympathetic nervous system in man

A model for assessing the effect of sympatholytic drugs on the peripheral sympathetic nervous system in man is described. Guanethidine, a sympatholytic drug, and the vehicle have been used to explore the model which is based on the Bier block. Sympathetic activity was assessed by measuring: (i) palmar sweating; (ii) skin temperature; (iii) radial/brachial pressure index; (iv) hand blood flow; and (v) vasoconstrictor ice response of hand blood flow. Neither the tourniquet nor the vehicle had any effect on sympathetic activity whereas guanethidine produced significant changes in skin temperature (P < 0.05), hand blood flow (P < 0.001) and the vasoconstrictor ice response (P < 0.002), illustrating the usefulness of the model.     

The role of the sympathetic nervous system in moxibustion-induced immunomodulation in rats

The effects of chemical sympathectomy on moxibustion-induced changes in splenic natural killer (NK) cell cytotoxicity, T and B cell proliferation were studied. Direct moxibustion was applied to the unilateral Zusanli region. NK cell cytotoxicity was suppressed by moxibustion in both vehicle-treated rats and sympathectomized rats. T cell proliferation was not affected by moxibustion. B cell proliferation showed no significant change in vehicle-treated rats, but an increase was seen in sympathectomized rats treated with moxibustion. Sympathectomy alone induced an augmentation of NK cell cytotoxicity and a suppression of T cell proliferation. These results suggest that the sympathetic nervous system (SNS) has no significant role in the mechanism of moxibustion-induced immunomodulation.     

Passive-avoidance learning after medial septal lesions: Effect of experience and the peripheral sympathetic nervous system

Prior studies from our laboratory suggest that peripheral sympathetic ingrowth, which occurs in the hippocampus following medial septal lesions, is detrimental to the reaquisition of a spatial learning/memory task. To assess the generality of this finding we studied step-through passive-avoidance learning in animals with a medial septal lesion with or without superior cervical ganglionectomy under two experimental conditions. In the first condition, in which no prior experience with the task occurred, animals with a lesion demonstrated facilitation of learning. In the second condition, in which animals received pretraining with no shock prior to surgical manipulation, the behavior of animals with the lesion was similar to that of controls. No effect of ganglionectomy or initial sympathetic ingrowth was found in either condition. The results suggest that the effects of medial septal lesions on passive avoidance behavior are determined by the experimental condition and that early peripheral sympathetic ingrowth does not contribute either in a detrimental or beneficial fashion to passive avoidance learning.     

Effects of chronic lithium treatment on the peripheral nervous system.

BACKGROUND: Although lithium carbonate is widely used in the treatment of mood disorders, symptoms suggesting toxic effects on the peripheral nervous system may emerge even in subjects whose serum lithium levels remain within the recommended therapeutic range. METHOD: Electroneuronographic (ENG) parameters (motor nerve conduction velocity of peroneal and median nerves, sensory nerve conduction velocity of sural and median nerves, amplitude of motor potential of peroneal and median nerves, and amplitude of sensory action potential of the median nerve at the wrist and the sural nerve) were investigated in 2 groups (N = 34) of patients suffering from bipolar affective disorder (DSM-III-R, DSM-IV) undergoing maintenance treatment with lithium carbonate for at least 1 year (mean = 2.06 years) in monotherapy. For 12 patients, ENG results were compared with pretreatment values, whereas in the other 22 cases, only data relevant to posttreatment were available. Fifty-four healthy subjects and 20 patients with recurrent major affective disorder (unipolar and bipolar) never treated with lithium made up the comparison groups. RESULTS: Compared with the 2 comparison groups, patients on chronic lithium treatment showed significant reduction of motor nerve conduction velocity of peroneal and median nerves, sensory nerve conduction velocity of sural and median nerves, amplitude of motor potential of peroneal and median nerves, and amplitude of sensory action potential of the median nerve at the wrist and the sural nerve. The comparison with the assessment made prior to lithium treatment also showed significant changes; after a period of treatment with lithium varying from 2 to 8 years (mean = 5.2 years), significant reductions were found on motor and sensory nerve conduction velocity and on amplitude motor potentials and sensory action potentials. CONCLUSION: Chronic maintenance treatment with lithium affects the peripheral nerves, even if the impairment rarely is such as to warrant discontinuation of treatment. Monitoring of ENG results could be useful for the early detection of neurotoxicity of lithium.     

Quantitation and localization of 204thallium in the central and peripheral nervous system of adult and young rats

A single dose of 204Tl, representing about 2-3 ng 204Tl per gm/wt was injected into young and adult rats. Rats were killed daily over a period of 10 days and the levels of Tl were estimated in nervous and other tissues. The greatest concentrations of Tl (peak concentration time - PCT) in all tissues in the adult rat occurred 24 hours after injection. In the young rat PCT in the sciatic nerve and spinal cord were 48 hours after injection whereas it occurred 24 hours after injection in the brain and somatic organs. There were differences in biological half-lives of the organs in the young as compared to the adult rats. Tl level in all organs except the kidney, were about 2 pg/mg of tissue. It was concentrated in the cytoplasm of most cells examined. Tl levels then fell rapidly during the few days following the injection, and slowly afterwards. Thirty days after the injection, tracts of 204Tl were present in the cytoplasm of nervous and somatic cells.     

Bombesin-induced hypothermia in rats tested at normal ambient temperatures: Contribution of the sympathetic nervous system

Rats infused centrally with bombesin become hypothermic at normal ambient temperatures when acutely deprived of food, but not while allowed unrestrained access to food. Ad lib-fed rats, tested at normal ambient temperatures, become hypothermic after receiving intracerebroventricular (ICV) bombesin when they have ventromedial hypothalamic lesions or when administered insulin or 2-deoxy-d-glucose peripherally. All of these conditions have been linked to reductions of sympathetic nervous system activity to brown adipose tissue (BAT), a major thermogenic mechanism of many homeotherms. A between group design was used to examine the effects of ICV bombesin infusions on the response to peripheral injections of a) the sympathetic ganglionic blocker chlorisondamine (2.5 mg/kg, IP) in ad lib-fed rats, b) the nonspecific β-agonist isoproterenol (30 mg/kg, IP) in food-deprived rats, and c) the combination of isoproterenol and chlorisondamine in ad lib-fed rats. Ad libfed rats receiving ICV bombesin (100 ng/5 μl), in combination with peripheral chlorisondamine injection, became hypothermic 60 min postbombesin administration (−2.84 ± 0.33°C), while ad lib-fed rats receiving ICV bombesin infusion and peripheral injections of saline did not (−0.08 ± 0.37°C). Isoproterenol blocked hypothermia in ad lib-fed rats injected with chlorisondamine and ICV bombesin. Food-deprived rats receiving ICV bombesin infusion and peripheral saline injection exhibited hypothermia 60 min postbombesin administration (−2.51 ± 0.29°C). Peripheral injections of isoproterenol prevented bombesin-induced hypothermia in food-deprived rats. These data suggest that bombesin induces hypothermia at normal ambient temperatures when the sympathetic nervous system drive to BAT cannot be (or is not) activated.     

The peripheral sympathetic nervous system. Its role in normal and pathologic anxiety

Acute emotional arousal, regardless of the emotional state, increases sympathetic activity. The sympathetic response, however, does not lead to a uniform change in all sympathetically innervated systems. The response magnitude of specific systems, such as the cardiovascular system, depends to a large extent on constitutional and hereditary factors. The subjective awareness of bodily changes accompanying heightened sympathetic activity is inaccurate; people often recognize the direction but not the degree of change. The level of body awareness depends on various psychologic factors, of which anxiety plays an important role. Acute stress produces sympathetic activation in nonanxious as well as anxious persons. Nonanxious persons tend to have more flexible autonomic responses. They show stronger responses to novel situations but return to lower autonomic levels earlier and habituate faster than do anxious persons. That is, nonanxious persons possess a greater autonomic flexibility than anxious persons. It is important to know the physiologic state of anxiety disorder patients during periods when they do not feel anxious, during times of heightened tension, during the performance of standardized stress tasks, during exposure to psychopathology-specific stressors, and during "spontaneously" occurring surges of anxiety, such as panic attacks. At present only limited information concerning these conditions is available. There is little evidence that anxiety disorder patients, perhaps with the exception of very severe cases, have an increased sympathetic tone when they do not feel anxious. However, all anxiety disorders, with the exception of simple phobia, show some sort of physiologic activation in threatening situations, including the recording of physiologic baseline values in laboratories. The type of activation differs among anxiety disorders. During periods of rest, social phobics and panic disorder patients tend to show sympathetic activation, generalized anxiety disorder patients show increased muscular tension without sympathetic activation, and obsessive-compulsive patients show increased muscular tension along with sympathetic inhibition. Under laboratory stress, both normals and anxiety disorder patients react with sympathetic arousal. However, in generalized anxiety and obsessive-compulsive patients the response is weaker than in normals, suggesting the presence of an inhibitory process. Thus, the autonomic flexibility of anxiety disorder patients is reduced.(ABSTRACT TRUNCATED AT 400 WORDS)     

Central nervous system circuitry and peripheral neural sympathetic activity responsible for essential hypertension

Both clinical and experimental studies dealing with patients affected by idiopathic or essential hypertension (EH) are devoted to the great deal of physiological, pharmacological and pathological as well as therapeutical issues of EH. However, most articles devoted to EH do not refer to the central nervous system mechanisms underlying this disease and the channels which allow that these mechanisms are funneled to the peripheral autonomic nervous system and trigger this cardiovascular disorder. In the present review article we attempted to reach this target devoted to the central nervous system circuitry involved in the cardiovascular pathophysiology. We postulated that EH depends on the predominance of the binomial A5 noradrenergic (NA) nucleus + median raphe serotonergic (5-HT) nucleus over the (A6)-NA + dorsal raphe-5HT nuclei. This hypothesis receives additional support from our results obtained throughout the neuropharmacological therapy of this type of neurophysiological disorder. Our therapeutical strategy is addressed to enhance the activity of the (A6)-NA + dorsal raphe-5HT binomial circuitry.     

Imaging of the autonomic nervous system: focus on cardiac sympathetic innervation

Symptoms or signs of abnormal autonomic nervous system function occur commonly in several neurological disorders. Clinical evaluations have depended on physiological, pharmacological, and neurochemical approaches. Recently, imaging of sympathetic noradrenergic innervation has been introduced and applied especially in the heart. Most studies have used the radiolabeled sympathomimetic amine, (123)I-metaiodobenzylguanidine. Decreased uptake or increased "washout" of (123)I-metaiodobenzylguanidine-derived radioactivity is associated with worse prognosis or more severe disease in hypertension, congestive heart failure, arrhythmias, and diabetes mellitus. This pattern may reflect a high rate of postganglionic sympathetic nerve traffic to the heart. Many recent studies have agreed on the remarkable finding that all patients with Parkinson's disease and orthostatic hypotension have a loss of cardiac sympathetic innervation, whereas all patients with multiple system atrophy, often difficult to distinguish clinically from Parkinson's disease, have intact cardiac sympathetic innervation. Because Parkinson's disease entails a postganglionic sympathetic noradrenergic lesion, the disease appears to be not only a movement disorder, with dopamine loss in the nigrostriatal system of the brain, but also a dysautonomia, with noradrenaline loss in the sympathetic nervous system of the heart. As new ligands are developed, one may predict further discoveries of involvement of components of the autonomic nervous system in neurological diseases.     

Essential hypertension and the sympathetic nervous system

Cryptoccus neoformans meningitis (CNM) is an opportunistic infection that typically occurs in immunosuppressed patients. Subjects affected by sarcoidosis, a systemic granulomatous disease of unknown cause, are predisposed to CNM because of the impairment of cell-mediated immunity and because of the chronic corticosteroid therapy they frequently receive. Here we report the case of a 38-year-old man who developed CNM as the first clinical manifestation of sarcoidosis. The patient developed CNM even though he was apparently immunocompetent and was not on therapy with either corticosteroid or cytotoxic drugs.

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Sommario La meningite da Cryptoccus neoformans colpisce tipicamente soggetti immunodepressi tra cui i pazienti affetti da sarcoidosi. In particolare, si ritiene che questi ultimi siano predisposti a sviluppare una meningite criptococcica sia a causa della compromissione dell’immunità cellulo-mediata sia a causa della terapia corticosteroidea cui sono frequentemente e cronicamente sottoposti. Il caso che presentiamo riguarda un paziente di 38 anni che ha sviluppato una meningite criptococcica come prima manifestazione clinica della sarcoidosi. Ciò che, a nostro giudizio, rende meritevole di segnalazione questo caso, è il fatto che il paziente, oltre a non aver mai manifestato alcun segno clinico di sarcoidosi, era apparentemente immunocompetente e non era mai stato sottoposto ad alcun trattamento cronico con corticosteroidi.

     

The sympathetic nervous system of anamniotes

The sympathetic nervous system develops as an evolutionary trait with gnathostomes (jawed vertebrates), but not with agnathan fishes (i.e., hagfishes and lampreys). Organization of the sympathetic preganglionic neuronal columns is different in teleosts and anurans. In the teleosts so far examined, the majority of sympathetic preganglionic neurons (SPNs) are located in the dorsal part of the spinal central gray matter. In Tetraodontiformes, the cell column occupies only two rostral spinal segments, which are distinct in their cytoarchitecture and projections. On the other hand, the SPNs of anurans form two cell columns segregated mediolaterally. The lateral and medial columns are also distinct in their cytoarchitecture and projections. The neuroactive substances expressed in the SPNs both in teleosts and anurans are coded to the projections. In anurans, the SPNs containing gonadotrophin-releasing hormone and those containing calcitonin gene-related peptide are involved in the regulation of blood vessels and cutaneous glands, respectively. In the filefish, the SPNs containing galanin project specifically to non-adrenergic non-cholinergic postganglionic neurons in the cranial sympathetic ganglia. Therefore, both anuran and teleost systems have different morphological and chemical-coded patterns for functional variation, although the anuran sympathetic nervous system has more organizational similarity with that of amniotes.