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Effect of peripheral nerve lesion and lumbar sympathectomy on peptide regulation in dorsal root ganglia in the NGF-overexpressing mouse.

Galanin is a peptide normally expressed at low levels both in sensory and in sympathetic neurons. It is strongly upregulated after peripheral nerve lesions, and it has been proposed that nerve growth factor (NGF) plays a role in this regulation. In the present study the effect of both sciatic nerve transection and lumbar sympathectomy on galanin in lumbar dorsal root ganglia (DRGs) was examined in mice overexpressing NGF (NGFOE) in the skin under the keratin promoter. The superior cervical ganglia (SCG) were also studied. In the DRG pericellular baskets containing tyrosine hydroxylase- (TH) and galanin-like immunoreactivity (LI) were found, mostly in the same fibers. Galanin-positive baskets were also found in the trigeminal ganglia. However, only single neuropeptide Y (NPY)-positive baskets were observed within the DRGs. No marked difference in number of galanin-positive neurons was seen between wild-type and NGFOE mice. After sciatic nerve transection galanin was upregulated in DRG neurons to about the same extent in NGFOE mice as in wild-type mice. Galanin-, but not TH-LIs decreased in the pericellular baskets. After lumbar sympathectomy both galanin- and TH-immunoreactive baskets disappeared, suggesting a sympathetic origin. In the SCG the very low galanin mRNA levels were strongly increased after lesion of the carotid nerves, both in wild-type and in NGFOE mice. However, whereas NPY mRNA levels decreased in the SCG after axotomy in the wild-type mice, there was a distinct increase in the NGFOE mice. Our results show that high NGF levels in skin induce formation of pericellular baskets in DRGs expressing galanin- and TH-LI and that galanin in these baskets is strongly influenced by peripheral axotomy. However, overexpression of NGF did not markedly influence galanin expression in DRG neurons, neither normally nor after nerve lesions. Finally, expression of NPY in sympathetic ganglia is differently regulated in NGFOE compared to wild-type mice.

Animals↗

Evidence that nitric oxide-induced synthesis of cGMP occurs in a paracrine but not an autocrine fashion and that the site of its release can be regulated: studies in dorsal root ganglia in vivo and in vitro.

As nitric oxide is a gas, it cannot be stored and has to be synthesized as required. This suggests that it could be released wherever nitric oxide synthase (NOS) is activated and due to its unstable state will react with appropriate targets at this site of production. In both dissociated dorsal root ganglion (DRG) cultures and in acutely isolated, but intact, DRG, treatment with capsaicin or bradykinin caused cGMP synthesis, which could be blocked by NOS inhibitors. The cGMP was synthesized in cells different from those expressing the neuronal isoform of NOS (nNOS). In dissociated cultures many of the cells stimulated to produce cGMP were neurons, whereas in isolated ganglia they were always satellite glia cells. Surprisingly, the satellite glia cells surrounding the nNOS-containing neurons did not contain cGMP. Following nerve section in adult rats, many axotomized ganglion neurons expressed nNOS. Again in these axotomized ganglia, most cGMP was expressed in the satellite glia surrounding nNOS-negative neurons. However, an nNOS-selective inhibitor reduced the cGMP present in these axotomized ganglia, suggesting that the cGMP synthesized is stimulated by NO (nitrogen monoxide) produced by nNOS. In both dissociated cultures and axotomized ganglia, nNOS-containing processes were observed close to cGMP-positive cells. These observations lead to the suggestion that NO acts in a paracrine fashion when stimulating the synthesis of cGMP and may not be synthesized at all sites containing nNOS.

Animals↗

Simian varicella virus infects ganglia before rash in experimentally infected monkeys.

Monkeys experimentally infected with simian varicella virus (SVV) develop rash 10-14 days later. However, the route and the time of ganglionic infection are unknown. Using PCR, we analyzed DNA extracted from tissues of 13 monkeys 5 to 60 days after either intratracheal or intravenous inoculation with SVV. SVV DNA was detected in ganglia from four of five monkeys sacrificed 6 to 7 days after intratracheal inoculation. Further, analysis of ganglia from monkeys sacrificed at 10 days revealed that intravenous inoculation produced a higher proportion of SVV DNA-positive ganglia (63%) than that after intratracheal inoculation (13%), pointing to the role of hematogenous spread in ganglionic infection. Like other organs, monkey ganglia become infected with SVV before the appearance of rash.

Animals↗

Relationship between axonal collateralization and neuronal degeneration in basal ganglia.

In this paper we evaluate the hypothesis of a possible link between the degree of axonal collateralization of neurons located within the different components of basal ganglia and the vulnerability of these neurons to neurodegenerative or neurotoxic events. Our results stemmed from single-cell labeling experiments in rodents and primates, immunohistochemical study of the dopaminergic nigrostriatal pathway in parkinsonian monkeys, and immunocytological analysis of the human striatum in normal individuals and in patients with Huntington's disease. Our results indicate that projection neurons within virtually all basal ganglia components are endowed with a widespread and highly collateralized axon that yields a fixed number of terminals. Such a high degree of axonal collateralization allows exquisitely precise interactions between the various basal ganglia nuclei. However, the maintenance of this unique morphological trait implies high-energy consumption and renders basal ganglia neurons highly vulnerable to neurodegenerative, metabolic or neurotoxic insults.

Animals↗

Functional and morphological evidence for the existence of neurites from abdominal ganglion bag cell neurons in the head-ring ganglia of Aplysia.

Three lines of evidence are presented indicating that axons of the Aplysia neuroendocrine bag cells extend into the head-ring ganglia of the CNS. When the abdominal ganglion was bisected longitudinally, separating the two bag cell clusters, an afterdischarge induced in one cluster generated an afterdischarge in the other via activity through the head-ring ganglia to which each half abdominal ganglion was attached by connective nerves. This suggests that some axons of bag cells in each cluster communicate through the head-ring ganglia. Retrograde labelling of bag cells occurred when rhodamine-conjugated latex microspheres were injected into the cerebral or either pleural ganglion, a direct demonstration that bag cell axons extend into these ganglia. Finally, cell LP1 in the left pleural ganglion was inhibited during a bag cell afterdischarge, an action mimicked by application of alpha-bag cell peptide (alpha BCP). Since alpha BCP can act only close to its site of release due to susceptibility to peptidase activity, it is likely that LP1 inhibition is dependent on the local release of alpha BCP from bag cell neurites in the pleural ganglion. These results open new possibilities for how bag cell afterdischarges may be initiated and broaden the distribution of their effects.

Abdomen↗

Control of feeding movements in the freshwater snail Planorbis corneus. I. Rhythmical neurons of buccal ganglia.

(1) The buccal mass of the freshwater snail Planorbis corneus, dissected together with the buccal ganglia, performs rhythmic feeding movements. Radula movements and the electrical activity in various nerves of buccal ganglia were recorded in such a preparation. The cycle of radula movements consisted of three phases: quiescence (Q), protraction (P) and retraction (R). The activity in the radular nerve was observed mainly in the P-phase and that in the dorsobuccal nerve, largely in the R-phase. (2) Isolated buccal ganglia were capable of generating a feeding rhythm, the activity in buccal nerves being similar to that observed in the buccal mass-buccal ganglion preparation, i.e., a burst in the radular nerve preceded a burst in the dorsobuccal nerve. The activity of neurons in isolated buccal ganglia during generation of the feeding rhythm has been studied with intracellular microelectrodes. About 10% of ganglion neurons exhibited periodic activity related to the feeding rhythm ("rhythmic" neurons). (3) Rhythmic neurons have been divided into 7 groups according to the phase of their activity and to the characteristics of slow oscillations of the membrane potential during the feeding cycle. Group 1 neurons revealed a gradual increase of depolarization during the Q- and P-phases. In subgroup 1e neurons, spike discharges began in the Q-phase, while in subgroup 1d neurons activity started in the P-phase. During the R-phase, group 1 neurons were strongly hyperpolarized, and their discharges terminated. In group 2 neurons, small depolarization gradually increased during the Q- and P-phases. Then, in the R-phase, a large (20-50 mV) rectangular wave of depolarization arose with superimposed high-frequency oscillations. Group 3 neurons exhibited an excitatory postsynaptic potential (EPSP) in the P-phase and inhibitory postsynaptic potential (IPSP) in the R-phase. The neurons of group 4 revealed two EPSPs: a small one in the P-phase and a larger one in the R-phase. Group 5 neurons exhibited an EPSP in the P-phase, those of group 7 - an IPSP in the R-phase, and those of group 9 - IPSPs in the P- and R-phases. Neurons within each of the groups 1, 2 and 4 were electrically coupled, and in addition, there were also electrical connections between neurons of groups 2 and 4. (4) Data are presented showing that neurons of groups 1 and 2 are the main source of postsynaptic potentials in rhythmic neurons in the P-phase and in the R-phase of the cycle, respectively.

Action Potentials↗

Effect of preganglionic sympathectomy on the cholinesterase activity in the superior cervical ganglia of rats and hamsters.

By employing biochemical assay and histochemical enzyme techniques the effect of preganglionic sympathectomy on the cholinesterase (ChE) activity in the superior cervical ganglia of rats and hamsters was investigated. Biochemical assays indicate that the ChE activity in the superior cervical ganglia of adult rats and hamsters is 57.19 and 28.63 respectively (expressed in micron moles acetylcholine hydrolyzed per min per g of tissue); two weeks after preganglionic denervation, about 50% and 60% of ChE activity are lost respectively. Histochemical enzyme examination reveals that in the rat superior cervical ganglion, the majority of the neurons are adrenergic with weak to moderate acetylcholinesterase (ACHhE) reaction and the minority of the neurons are cholinergic with strong AChE activity, while only one type of adrenergic neurons exhibits a weak AChE activity in the hamster superior cervical ganglion. The AChE activity is localized in the perinuclear area, in the cisternae of the rough surfaced endoplasmic reticulum, in the Golgi complex and on the plasma membrane of the hamster's neurons; it is mainly locolized in the cisternae of the rough surfaced endoplasmic reticulum of the rat's neurons. AChE reaction product is also detected on the aeolemmal membranes of the preganglionic nerve fibers in the sympathetic ganglia of rats and hamsters. After preganglionic sympathectomy, the AChE activity in the adrenergic neurons and in the preganglionic unmyelinated nerve fibers is markedly reduced, whereas the cholinergic neurons and preganglionic myelinated nerve fibers remain unchanged. On the basis of these results two conclusions have been reached: (1) The fact that strong AChE activity localized in the cholinergic neurons and preganglionic myelinated fibers is not influenced by denervation, suggests that these structures are able to produce AChE. (2) The reduction of AChE activity in the rat and hamster superior cervical ganglia two weeks after preganglionic denervation, observed by histochemical examination, can be correlated with a concomitant measurable reduction determined by biochemical assays.

Acetylcholinesterase↗

Distribution of NADPH-diaphorase activity in rat paravertebral, prevertebral and pelvic sympathetic ganglia.

Paravertebral (superior cervical and stellate), prevertebral (coeliac-superior mesenteric, inferior mesenteric) and pelvic (hypogastric) sympathetic ganglia of the rat were investigated by enzyme histochemistry to ascertain the distribution of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) activity. In the paravertebral ganglia the majority of the sympathetic neuronal perikarya contained lightly and homogeneously distributed formazan reaction product but there was a range of staining intensities amongst the neuron population. In contrast, in the prevertebral ganglia, intense NADPH-diaphorase staining was present in certain neurons. Firstly, a population of neurons of the coeliac-superior mesenteric ganglion complex were surrounded by densely NADPH-diaphorase-positive 'baskets' of fibres and other stained fibres were seen in interstitial nerve bundles and in nerve trunks connected to the ganglion complex. Secondly, in both the inferior mesenteric ganglion and hypogastric ganglion there were many very intensely NADPH-diaphorase positive neurons. Stained dendritic and axonal processes emerged from these cell bodies. In both ganglia this population of neurons was smaller in size than the lightly stained ganglionic neurons and commonly had only one long (presumably axonal) process. The similarity of these highly NADPH-diaphorase-positive neurons with previously described postganglionic parasympathetic neurons in the hypogastric ganglion is discussed.

Animals↗

Differential effects of methylmercury on the synthesis of protein species in dorsal root ganglia of the rat.

Dorsal root ganglia from control and methylmercury (MeHg)-treated rats were incubated in vitro with 35S-methionine ant the proteins synthesized were analyzed by two-dimensional electrophoresis. The double labelling method, in which proteins of control dorsal root ganglia labelled in vitro with 3H-leucine were added to each of the two samples as an internal standard, was used to minimize unavoidable errors arising from the resolving procedure itself. The results obtained showed that the effect of MeHg on the synthesis of proteins in dorsal root ganglia was not uniform for individual protein species in the latent period of MeHg intoxication. Among 200 protein species investigated, 157 showed inhibition of synthesis close to that of the total proteins in the tissue (68% of the control). Among the remaining protein species, 20 showed real stimulation of synthesis, whereas 7 were moderately inhibited and 16 were inhibited more strongly than the total proteins in the tissue. These results suggest that the effect of MeHg on the synthetic rates for protein species in dorsal root ganglia differs with the species, and that unusual elevation or reduction of the synthesis of some protein species caused by MeHg may lead to impairment of normal nerve functions.

Animals↗

Distribution of enteric nerve cells projecting to the superior and inferior mesenteric ganglia of the guinea-pig.

Retrograde tracing, using Fast Blue dye, was employed to determine the distribution of enteric nerve cells that project to the superior mesenteric and inferior mesenteric ganglia of the guinea-pig. Retrogradely labelled neurons were found in the myenteric but not submucous ganglia. When the superior mesenteric ganglion was injected, labelled neurons were found in low frequencies (less than 5 nerve cell bodies/cm2) in the duodenum, jejunum, ileum, caecum and proximal colon. The distal colon was analysed in five segments of equal length (1-5; oral to anal). Segment 1 had about 4 labelled nerve cells/cm2, whereas segments 2 to 5 displayed an average of about 25 nerve cells/cm2. The rectum contained about 36 labelled neurons/cm2. After injection of the inferior mesenteric ganglia with Fast Blue, no labelled neurons were found in the duodenum, jejunum, ileum or caecum. No labelled cells were observed in the gallbladder. A small number of labelled cells occurred in the proximal colon and in segment 1 of the distal colon. The frequency of labelled cells increased markedly in the more anal regions of the distal colon, and reached a peak in the rectum (138 cells/cm2). Both nerve lesions and immersion of the cut nerve in Fast Blue solution showed that the superior mesenteric nerve carries the axons of neurons located in the middle distal colon to the superior mesenteric ganglion. Almost half of the neurons in the rectum that project to the inferior mesenteric ganglia do so via the hypogastric nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

[Results of a study of a family with aggregated occurrence of bilateral symmetrical basal ganglia calcinosis].

We present a familial study (45 members), in which 31 members have been examined. Seven were afflicted with bilateral symmetrical calcification of the basal ganglia (Fahr's syndrome), as verified by CT scans. The case history and biochemical results for one additional proband, who had died, strongly indicate that this patient also had Fahr's syndrome. The wide range of examinations used in our study were aimed at excluding differential diagnoses of bilateral symmetrical calcification of the basal ganglia, other than when the origin was suspected to be in the parathyroid. The examinations had to be undertaken on an outpatient basis. Some of the variables, such as Fe, Cu, and Mg in the plasma, are connected with results that have been published on the composition of the apatite deposits. Psychiatric, psychological, neurological, and EEG examinations are emphasized. Together with the case reports they are meant to illustrate the neuropsychiatric aspects of this syndrome, the composite view of which has often been previously neglected. Nineteen of 31 probands showed neurological, psychopathological, psychological, and encephalographical deviations. We also noted a high incidence of organic brain syndromes that are phenomenologically similar to affective disorders. We believe these deviations to be directly related to morphological alterations of the basal ganglia, possibly due to errors in phosphorous and calcium metabolism. Although the CT scan has greatly facilitated the diagnosis of intracerebral calcifications, we assume that basal ganglia alterations under the CT-density threshold may also be of clinical importance. Our metabolic results, genetic issues, and neuropsychiatric findings are discussed.

Adolescent↗

Mechanisms of tyrosine hydroxylase and dopamine beta-hydroxylase induction in organ cultures of rat sympathetic ganglia by potassium depolarization and cholinomimetics.

It was the aim of the present study to elucidate the mechanisms involved in specific tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) induction by potassium depolarization and cholinomimetics in rat superior cervical ganglia kept in organ culture. The effect of high (54 mM) potassium concentration on intact ganglia seems to result in a dual action: a) a specific induction of TH and DBH via release of acetylcholine from preganglionic cholinergic nerve terminals. b) a non-specific effect on terminal adrenergic neurons resulting in a general increase of protein synthesis as indicated by the increase in DOPA decarboxylase (DDC) and monoamine oxidase (MAO) activities. In decentralized superior cervical ganglia potassium depolarization failed to produce the specific TH and DBH induction although a small increase in DDC activity persisted. Carbamylcholine, acetylcholine and nicotine at concentrations of 10(-4) M elicited a selective induction of TH and DBH both in intact and decentralized ganglia via nicotinic receptor stimulation. Bethanechol, predominantly stimulating muscarinic receptors had no significant effect on TH activity. A 4 h pulse of 10(-4) M carbamylcholine produced optimal induction of DBH and TH 24 h and 48 h later respectively. Longer exposure to carbamylcholine resulted in a significantly smaller rise in TH activity.

Acetylcholine↗

Immunohistochemical detection of ganglia in the rat stomach serosa, containing neurons immunoreactive for gastrin-releasing peptide and vasoactive intestinal peptide.

Ganglia, not previously described, were identified in the rat stomach serosa along the minor curvature. The ganglia consisted of varying number of cell bodies lying in clusters along or within nerve bundles. The ganglia were shown to contain GRP and VIP immunoreactive nerve fibers and cell bodies and also some NPY immunoreactive fibers, whereas they were devoid of somatostatin immunoreactivity. Nerve ligation experiments indicated that the ganglia are intrinsic to the stomach.

Animals↗

Neurological disorders in 166 patients with basal ganglia calcification: a statistical evaluation.

Patients investigated at our institute during the last decade included 166 (1.2%) who showed uni- or bilateral basal ganglia calcification on computed tomography. We tested the significance of this neuroradiological observation by statistical comparison of these patients' clinical disorders with the findings in a random sample of 622 patients without basal ganglia calcification. The odds for the most common neurological disturbances were similar in patients with and without basal ganglia calcification. After adjustment for differences in age and brain atrophy there was no evidence of a significantly increased risk of dementia (odds ratio 1.1), cerebral infarction (1.4), epilepsy (0.9), vertigo (1.6), headache (1.8), or alcoholism (0.9), which represented the most common diagnoses. We conclude that basal ganglia calcification cannot be considered as a clinically relevant neuroradiological finding in the majority of cases and that it should not be used as an explanation for frequently observed neurological disturbances.

Basal Ganglia Diseases↗

Phosphorylated neurofilament epitopes in neuronal perikarya in the septum, mesencephalon and dorsal root ganglia of mammals and birds.

We and other researchers have previously described the presence of axon-specific phosphorylated neurofilament epitopes in the cell bodies of three neuronal types in the rat: bipolar septofimbrial neurons and the large light A-type cells in the dorsal root ganglia and the mesencephalic nucleus of the Vth nerve. This spontaneous presence of phosphorylated neurofilaments at the level of the perikaryon contrasts with the induced appearance of these epitopes in axotomized neurons. We have undertaken a study of this phenomenon in rat, mouse, gerbil, rabbit, pig and chicken to analyse its species distribution. Phosphorylated neurofilament positive perikarya could be detected in the dorsal root ganglia and mesencephalic nucleus of the Vth nerve in all analysed species. Although this labelling has been shown to be specific for A-type cells in rat, in pig small cells were preferentially labelled, whereas the largest cells were mostly completely devoid of label. In the septofimbrial nucleus, phosphorylated neurofilament positive perikarya were seen in rat, mouse, gerbil and rabbit. In the pig, only a phosphatase-insensitive neurofilament antibody labelled these neurons. In the chicken, the labelling was completely absent. These observations establish the widespread species distribution of perikaryal phosphorylated neurofilament epitopes in the dorsal root ganglia and mesencephalic nucleus of the Vth nerve. In the septofimbrial nucleus however, this phenomenon seems to be restricted to rodents and lagomorphs. We discuss possible explanations for these cytoskeletal singularities in dorsal root ganglia, the mesencephalic nucleus of the Vth nerve and septofimbrial neurons.

Animals↗

Cytochemical localization of 5'-nucleotidase in the enteric ganglia and in smooth muscle cells of the guinea-pig.

Cytochemical techniques were used to study the localization of 5'-nucleotidase in the enteric ganglia and in smooth muscle cells of the guinea-pig ileum, iris and vas deferens. Enzymatic activity was revealed in plasma membranes and caveolae of smooth muscle cells and in neurons and neuroglia of the enteric ganglia. The strongest activity was seen in the membrane of the smooth muscle cells, especially the caveolae intracellulares, and this was interpreted to indicate a high level of purine utilization and involvement in calcium translocation by these cells. The ganglia displayed enzymatic activity in the membranes of non-specialized neuron-to-glia boundaries as well as at some synaptic specializations. This finding is consistent with a possible release of adenine nucleotides within the ganglia.

5'-Nucleotidase↗

A comparison of four techniques for mapping the distribution of serotonin and serotonin-containing neurons in fixed and living ganglia of the snail, Lymnaea.

The distribution of serotonin and serotonin-containing neurons was studied in the ganglia of the CNS of the snail Lymnaea stagnalis. Results of the application of three different labelling techniques on wholemount preparations were compared with each other and with the serotonin content of the ganglia, measured by high-performance liquid chromatography. Serotonin immunocytochemistry resulted in the highest number of labelled neurons, but the more recently developed in vivo method of 5,6- or 5,7-dihydroxytryptamine-induced pigmentation also proved to be a reliable technique for the visualization of serotonin-containing cell bodies. In comparison with these two techniques, the glyoxylic acid fluorescence method appeared to be less sensitive. The distribution and number of serotonin-containing neurons and biochemically measured serotonin in specific ganglia showed a close correlation. By combining the results of the three labelling techniques, a detailed map of serotonin-containing neurons was constructed, and this was compared with maps of identified neurons prepared from earlier electrophysiological studies. Previously described serotonergic neurons were consistently found, as well as several new serotonin-containing cell types in the cerebral, visceral and parietal ganglia. A network of serotonin-containing inter- and intraganglionic axon tracts, and thin serotonergic fibres in the perineurium were also demonstrated. This in vivo and in vitro identification of serotonin-containing neurons will facilitate further neurophysiological analysis of serotonergic neural mechanisms in Lymnaea.

5,6-Dihydroxytryptamine↗

Effects of ageing on the histochemically demonstrable catecholamines and acetylcholinesterase of human sympathetic ganglia.

The sympathetic ganglia of adult and aged humans were obtained during vascular, gynaecological and urological surgery, and studied using the formaldehyde-induced fluorescence (FIF) method for histochemical demonstration of catecholamines. Microspectrofluorimetry was applied to characterize the emission spectra of the flurophores. The sympathetic ganglia contained two types of cells exhibiting FIF: the adrenergic neurons and the small, intensely fluorescent (SIF) cells. The adrenergic neurons contained pigment granules exhibiting autofluorescence with emission maximum at 530---540 nm. The number of these granules increased with age while the FIF of the neurons decreased. In the oldest patients, most of the neurons in the sympathetic ganglia showed only pigment fluorescence but not FIF. The decrease of the perikaryonal catecholamine stores is interpreted as a degenerative change leading to impaired function of the neurons. The patterns of AChE did not change with age. The SIF cells were sparse and were mostly observed near the ganglia, forming paraganglia of varying size. Because of the rarity of the SIF cells, the effect of ageing could not be judged reliably.

Acetylcholinesterase↗