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PubMed1997

Differential regulation of substance P by all members of the nerve growth factor family of neurotrophins in avian dorsal root ganglia throughout development.

This study examined the effects of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 on substance P levels in dorsal root ganglia of the quail shortly after ganglia formation (stage 26, embryonic day 4.5), during the middle of development (stage 33, embryonic day 7.5) and during late development (stage 44, embryonic day 14). It has already been shown that nerve growth factor increases levels of substance P during the middle and late stages of development, and that messenger RNA for the neurotrophin receptors, trkA, trkB and trkC is present at all of these stages. Dorsal root ganglia were isolated, rinsed with defined medium to dilute endogenous neurotrophins and exposed to one of the neurotrophins for either 4 or 20 h. Substance P levels were quantitated using enzyme immunoassay. None of the neurotrophins had any effect on substance P levels in dorsal root ganglia obtained at stage 26 after either a 4 or 20 h exposure time. Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 all significantly increased levels of substance P after either a 4 h or 20 h incubation in ganglia obtained at stages 33 and 44. The effects of nerve growth factor and neurotrophin-3 were specific: increases in substance P were completely blocked by simultaneous exposure to antibodies against either nerve growth factor or neurotrophin-3. The absence of any effect of neurotrophins on substance P expression during early development was unexpected, since dorsal root ganglia exhibit substantial levels of substance P and receptors for the neurotrophins are present and are apparently functional. It was also surprising that brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 induced increases in substance P levels during the middle and late stages of development, since substance P was thought to be exclusively localized to small TrkA neurons in dorsal root ganglia. However, immunocytochemical examination of dorsal root ganglia at stages 33 and 44 revealed substance P-like immunoreactivity in larger neurons as well as in small neurons. The results of this study have shown that different cellular responses to neurotrophins, such as effects on survival and/or peptide expression, may be acquired with differing temporal patterns not strictly related to expression of their receptors. Further, the regulation of neuropeptide synthesis in dorsal root ganglia is not due to any one neurotrophic factor. and the factors that regulate expression during early development are still unknown.

Animals↗

PubMed1998

Microcircuitry of the direct and indirect pathways of the basal ganglia.

Our understanding of the organization of the basal ganglia has advanced markedly over the last 10 years, mainly due to increased knowledge of their anatomical, neurochemical and physiological organization. These developments have led to a unifying model of the functional organization of the basal ganglia in both health and disease. The hypothesis is based on the so-called "direct" and "indirect" pathways of the flow of cortical information through the basal ganglia and has profoundly influenced the field of basal ganglia research, providing a framework for anatomical, physiological and clinical studies. The recent introduction of powerful techniques for the analysis of neuronal networks has led to further developments in our understanding of the basal ganglia. The objective of this commentary is to build upon the established model of the basal ganglia connectivity and review new anatomical findings that lead to the refinement of some aspects of the model. Four issues will be discussed. (1) The existence of several routes for the flow of cortical information along "indirect" pathways. (2) The synaptic convergence of information flowing through the "direct" and "indirect" pathways at the single-cell level in the basal ganglia output structures. (3) The convergence of functionally diverse information from the globus pallidus and the ventral pallidum at different levels of the basal ganglia. (4) The interconnections between the two divisions of the pallidal complex and the subthalamic nucleus and the characterization of the neuronal network underlying the indirect pathways. The findings summarized in this commentary confirm and elaborate the models of the direct and indirect pathways of information flow through the basal ganglia and provide a morphological framework for future studies.

Animals↗

PubMed2000

Hemorrhages of dorsal root ganglia and spinal cord in congenitally hydrocephalic HTX rat.

The effects on the brain caused by hydrocephalus have been examined in detail. However, only little attention has been paid to the possibility that hydrocephalus may affect the spinal cord and the spinal ganglia via the spinal canal. Therefore, the present study focused on the pathological changes seen in the spinal cord and the dorsal root ganglia. A total of 651 congenitally hydrocephalic HTX rats were used in this study. The age ranged from postnatal day 0 to postnatal day 520. All of the HTX rats were from littermates raised in our laboratory. Macroscopic and microscopic investigations demonstrated hemorrhages of the dorsal root ganglia in 134 rats among the 235 affected HTX rats. The hemorrhages of the dorsal root ganglia were observed most frequently in the lumbar ganglia and, less frequently, in the cervical ganglia. Of the 134 rats with hemorrhages in the dorsal root ganglia, 34 rats had hemorrhages both in the spinal cord and in the dorsal root ganglia. The spinal cord hemorrhages were distributed mainly around the central canal and in the ventral parts of the posterior funiculus at the lower thoracic and upper lumbar cords. These hemorrhages were seen only in those rats having progressive hydrocephalus. These findings suggest that increased cerebrospinal fluid pressure can cause congestion of the radicular veins, leading to hemorrhages of the spinal cord and the dorsal root ganglia.

Animals↗

PubMed1997

Basal ganglia volume in adults with Down syndrome.

This study was designed to determine the effects of aging on the volume of the basal ganglia in individuals with Down syndrome (DS) and to examine the relationship between basal ganglia volumes, neuropsychological test performance, and dementia status in this population. Subjects were 32 adults with DS. Basal ganglia volumes from 22 of these subjects were compared with those of 22 cognitively-normal individuals, who were individually matched on age, sex, and race. Performance on neuropsychological tests was correlated with basal ganglia volumes for 32 individuals with DS, and basal ganglia volumes of five demented DS subjects were compared with those of 14 non-demented DS subjects. Results indicated larger putamen volumes in the DS subjects, despite significantly smaller total brain volumes. Volumes of caudate and globus pallidus did not differ between DS and control subjects. Although there were some significant correlations between basal ganglia volumes and age, neuropsychological test performance, and dementia status in the DS subjects, these associations appeared to be a reflection of neurodevelopmental or atrophic reductions in overall brain volume rather than a reflection of specific basal ganglia abnormality. Correlations between age and volumes of basal ganglia and total brain were not significantly greater in non-demented DS subjects than in control subjects. Results suggest that volume reductions of the basal ganglia are not a salient feature of aging or of the dementia associated with DS.

Adult↗

PubMed1998

A review of differences between basal ganglia and cerebellar control of movements as revealed by functional imaging studies.

The role of the basal ganglia and cerebellum in the control of movements is unclear. We summarize results from three groups of PET studies of regional CBF. The results show a double dissociation between (i) selection of movements, which induces differential effects in the basal ganglia but not the cerebellum, and (ii) sensory information processing, which involves the cerebellum but not the basal ganglia. The first set of studies concerned motor learning of a sequence of finger movements; there was a shift of activation in the anterior-posterior direction of the basal ganglia which paralleled changes in the motor areas of the frontal cortex. During new learning, the dorsolateral prefrontal cortex and striatum (caudate nucleus and anterior putamen) were activated. When subjects had to select movements, the premotor cortex and mid-putamen were activated. With automatic (overlearned) movements, the sensorimotor cortex and posterior putamen were activated. When subjects paid attention to overlearned actions, activation shifted back to the dorsolateral prefrontal cortex and striatum. The cerebellum was not activated when subjects made new decisions, attended to their actions or selected movements. These results demonstrate components of basal ganglia-(thalamo)-cortical loops in humans. According to earlier studies in animals we propose that the basal ganglia may be concerned with selecting movements or the selection of appropriate muscles to perform a movement selected by cortical areas (e.g. premotor cortex). Secondly, a visuomotor co-ordination task was examined. In the absence of visual control over arm movements, subjects were required to use a computer mouse to either generate new lines or to re-trace lines on a computer screen. The neocerebellum (hemispheres of the posterior lobe, cerebellar nuclei and cerebellar vermis), not the basal ganglia, was more engaged when lines were re-traced (compared with new line generation). Animal experiments have shown that error detection (deviation from given lines) and correction occurs during line re-tracing but not line generation. Our data suggest that the neocerebellum (not the basal ganglia) is involved in monitoring and optimizing movements using sensory (proprioceptive) feedback. Thirdly, the relative contribution of sensory information processing to the signal during active/passive execution of a motor task (flexion and extension of the elbow) was examined; it was found that 80-90% of the neocerebellar signal could be attributed to sensory information processing. The basal ganglia were not involved in sensory information processing. They may be concerned with movement/ muscle selection (efferent motor component); the neocerebellum may be concerned with monitoring the outcome (afferent sensory component) and optimizing movements using sensory (feedback) information.

Basal Ganglia↗

PubMed2004

Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat.

Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and "global activation". During SWA, there was coherence at approximately 1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at approximately 1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15-60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change.

Action Potentials↗

PubMed1996

A stereological analysis of the numerical distribution of neurons in dorsal root ganglia C4-T2 in adult macaque monkeys.

The numbers of neurons in dorsal root ganglia C4-T2 of adult monkeys (M. nemestrina) were estimated in celloidin-embedded material by means of the optical fractionator, a stereological procedures that combines the optical disector with a fractionator sampling scheme. On each side, counts of A-type, B-type, and total neurons were performed for the whole set of ganglia, as well as separately for ganglia C7, C8, and T1. Sampling and counting in this study were carried out with the help of an interactive computer system, the test grids being provided by the GRID general stereological software package (Olympus Denmark). The precision of the estimates for each animal was evaluated by computing the coefficient of error, which was kept at or below 0.10. The mean number of neurons on each side of the C4 - T2 set was 236,500 with a coefficient of variation among animals (CV) of 0.13. Of these neurons, 42% were A-type and 56% were B-type. Mean left-right differences among animals were below 1%, with low variability (CV = 0.07). The mean numbers of neurons in ganglia C7, C8, and T1 were, respectively, 46,000 (CV = 0.20), 51,000 (CV = 0.18), and 41,000 (CV = 0.22). Mean side differences for individual ganglia were 17%, 16%, and 12%, respectively, with high variability among animals. Intraanimal side differences were low for the whole set of ganglia (4%), as well as for the C7-T1 group (5%), but increased substantially when ganglia were considered separately (up to 17% on average in C7) or even in pairs of adjacent ganglia. These findings provide a quantitative frame for developmental or lesion studies in the peripheral somatosensory system of macaques, and warn against using single ganglia in studies requiring quantitative side comparisons.

Animals↗

PubMed2003

The AChE-positive ganglia in the trachea and bronchi of the cat.

The tracheal and bronchial parasympathetic ganglia in the cat were studied using the histochemical-tiocholine method of Koelle and Friedenwald and histological techniques. Intensively stained AChE-positive nerve structures, i.e., ganglia and nerve fibres on the wall of the trachea and bronchi, were observed. The ganglia were situated mainly on the dorso-lateral surface of these organs, but they were also present on the ventral surface. The largest ganglia were found in the vicinity of the vagus nerve branches and on the surface of the tracheal smooth muscle. Numerous ganglia (95-210) of different sizes (40 x 230 microm to 260 x 520 microm) and shapes (spindle, longitudinal, oval, elliptical and multiform) were interconnected by nerve fibres and formed a dense ganglionated plexus. The ganglia forming this nerve structure were located mainly on the level of intercartilaginous spaces. They received the nerve branches from the cervical and the upper thoracic branches of vagus nerve and cervical and upper thoracic segments of the sympathetic trunk. Similar AChE-positive ganglionated plexus containing 28-33 ganglia connected by nerve fibres was observed on the posterior wall of the bronchi. Histological investigations confirmed the presence of fascicles of nerve fibers and nerve cells aggregations in the external membrane of the trachea and bronchi. The ganglia consisted of 2-25 cells on the cross-section. They were located mainly on the level of intercartilaginous spaces and contained (except ganglionic neurocytes, nerve fibres) satellite cells and small blood vessels. All the ganglia had thin connective capsule.

Acetylcholinesterase↗

PubMed1977

Organ culture of rat superior cervical ganglia.

The maintenance of adrenergic function has been investigated in organ cultures of adult rat superior cervical ganglia. Tyrosine hydroxylase and monoamine oxidase activities decreased gradually through 72 hours of culture. Dopamine beta-hydroxylase activity gradually increased in the cultured ganglia to 150% of that seen in fresh ganglia after 14 hours in culture. The level of norepinephrine increased in the cultured ganglia to a maximum of 225% of that seen in control ganglia. The increases in both dopamine beta-hydroxylase activity and in norepinephrine levels required protein synthesis but they were not dependent on the presence of nerve growth factor. The accumulation of norepinephrine in the cultured ganglia could not be explained by an increased rate of amine synthesis. Turnover measurements suggest that the accumulation can be explained by a decreased rate of amine metabolism in the cultured ganglia. A comparison of the distribution of amine storage vesicles showed that the number of heavy vesicles was greater in cultured than in fresh ganglia. The results suggest that sympathetic ganglia develop an increased capacity for amine storage in culture and that this leads to an increase in intracellular levels of norepinephrine.

Animals↗

PubMed1995

Chemical anatomy of primate basal ganglia.

This paper provides an overview of the anatomical and functional organization of the most prominent chemospecific neuronal systems that compose the basal ganglia in primates. Emphasis is placed on the heterogeneity and diversity of small-molecule transmitters, neuroactive peptides and proteins used by basal ganglia neurons. Dopaminergic, serotoninergic and cholinergic neuronal systems are shown to comprise multiple subsystems organized according to highly specific patterns. These subsystems differentially regulate gene expression of several neuroactive peptides, including tachykinins, enkephalins, dynorphin, somatostatin, and neuropeptide Y, that are used by distinct subsets of basal ganglia neurons. Glutamatergic excitatory inputs establish distinct functional territories within the basal ganglia, and neurons in each of these territories act upon other brain neuronal systems through a GABAergic disinhibitory output mechanism. A striking complementary pattern of distribution of the calcium-binding proteins parvalbumin and calbindin D-28k is noted in all basal ganglia components. The limbic system-associated membrane protein (LAMP) is confined chiefly to basal ganglia sectors that are anatomically and functionally related to limbic system structures; these may serve as functional interfaces between the basal ganglia and the limbic system. The functional status of the various basal ganglia chemospecific systems in neurodegenerative diseases, such as Parkinson's disease and Huntington's chorea, is examined. It is concluded that these multiple transmitter-related systems cannot be analyzed separately as they form highly complex and interactive neuronal networks. These complexities should be taken into account to reach a better understanding of the functions of primate basal ganglia in health and disease.

Animals↗

PubMed1996

[Detection of latent herpes simplex virus in human vestibular ganglia].

Viral infections are considered to be one of the possible etiologies of vestibular neuronitis. Herpes simplex virus type 1 (HSV-1) is a likely candidate agent as this virus has a strong neurotropism, and can establish latent infections in the nervous system. However the existence of infections in the vestibular ganglia has not been established. In this study, 31 vestibular ganglia from autopsied adults were investigated. Polymerase chain reaction (PCR) was used to detect HSV-1 viral genomes, and reverse transcription-PCR (RT-PCR) and in situ hybridization (ISH) methods were employed to demonstrate latency associated transcripts (LAT) of HSV-1, which has been known to be latency specific. HSV-1 DNA was detected in 6 of 10 (60%) vestibular ganglia using the PCR method, and HSV-1 LAT was detected in 5 of 8 (63%) vestibular ganglia using the RT-PCR method. However, ISH showed that only 1 of 13 (7.7%) vestibular ganglia was HSV-1 LAT positive. In total only 1 of 3,830 (0.03%) neurons from 13 vestibular ganglia was found to be positive. The results indicate with certainty that HSV-1 does produce latent infections in human vestibular ganglia, and that the percentage of HSV-1 infected neurons is less than that of trigeminal ganglia. The results of this study also suggest that the rare presence of HSV-1 LAT in the ganglia may possibly correspond to the less frequent occurrence of vestibular neuronitis resulting from reactivation of HSV-1.

Adult↗

PubMed2000

Probing Ganglia Dissolution and Mobilization in a Water-Saturated Porous Medium using MRI.

Magnetic resonance imaging (MRI) is used to probe the evolution of geometric characteristics such as the volume, shape, surface area, and cluster size of octanol ganglia trapped in a model porous medium, in this case a packing of spheres, as they dissolve into a mobile aqueous phase. The resulting pore-scale information is used to assess various assumptions used in existing models of the dissolution process. Dissolution of the ganglia was characterized by a reduction in the overall number of ganglia with little effect on the shape and mean of the volume distribution of the ganglia. This apparently anomalous result is explained by dissolution of the ganglia until they reach a critical size, which is dependent on the structure of the pore space, at which point they are mobilized and subsequently removed from the porous medium. The shape of the entrapped ganglia is characterized by a fractal dimension in the range 2.2-2.3, suggesting that models which assume a Euclidean geometry for the entrapped ganglia are appropriate. No significant change in the shape of entrapped ganglia is observed during dissolution. In agreement with the results of earlier workers, most hydrocarbon ganglia exist as singlets within the pore structure. Copyright 2000 Academic Press.

Journal Article↗

PubMed2001

Strain differences in the toxicity of cadmium to trigeminal ganglia in mice.

Cadmium (Cd) is toxic to sensory ganglia in many animal species. Cadmium uptake is low in the central nervous system, but it distributes preferentially to peripheral sensory and autonomic ganglia. Strain differences have been demonstrated in the sensitivity of mice to Cd-induced hepatotoxicity, testicular toxicity, and teratogenicity. To study the sensitivity of different mouse strains to Cd toxicity in sensory ganglia, eight strains of mice (four sensitive to testicular toxicity: 129/SVIM, AKR/J, DBA/1J, and C57BR/J; and four resistant: Balb/C, C3H/HeJ, A/J, and C57BL/6J) were given 15 micromol CdCl(2)/kg iv. Trigeminal ganglia (TG) were harvested 24 h later and examined by light microscopy for pathologic lesions. Cadmium induced degeneration of ganglion cells in five strains, namely 129/SVIM, AKR/J, DBA/1J, C57BR/J, and C3H/HeJ mice. These are the same strains that show sensitivity to testicular toxicity, except for C3H/HeJ, which is resistant to testicular toxicity. Cd also induced focal hemorrhages around the ganglion cells and nerve fibers in two of these strains (129/SVIM and AKR/J) and scattered foci of necrosis in C3H/HeJ and 129/SVIM strains. There was no morphologic abnormality in three strains, namely Balb/C, A/J, and C57BL/6J. To examine the mechanism of these strain differences in toxicity, all eight strains of mice were given a nontoxic dose of Cd (0.4 micromol CdCl(2)/kg, 20 microCi (109)Cd/kg iv). Cadmium distribution to the brain and trigeminal ganglia was determined 30 min later by gamma scintillation spectrometry. Cadmium content in the brain was very low and did not differ among the eight strains. In contrast, Cd content was higher in trigeminal ganglia of four of the five strains showing trigeminal ganglia sensitivity than in the three strains showing resistance. In conclusion, the toxicity of Cd to trigeminal ganglia is different among various strains of mice. This strain difference in toxicity appears to be due, at least in part, to differences in the distribution of Cd to the ganglia, but it is clearly not the only factor.

Animals↗

PubMed2000

Persistent elevated expression of cytokine transcripts in ganglia latently infected with herpes simplex virus in the absence of ganglionic replication or reactivation.

Infection of mouse trigeminal ganglia by herpes simplex virus induces cytokine expression that persists long after infectious virus or viral antigens become undetectable. To examine mechanisms underlying this phenomenon, we used a thymidine kinase mutant, dlsptk, which fails to replicate in ganglia and does not reactivate upon ganglionic explant. Using quantitative reverse transcriptase-polymerase chain reaction assays, we found that levels of interferon-gamma and tumor necrosis factor-alpha transcripts in dlsptk-infected ganglia were lower than those in wild type-infected ganglia, but were significantly (eight- to 10-fold) higher than those in mock-infected ganglia from Day 3 to Day 100 postinfection. We also studied latency-associated transcript (LAT) negative mutants that exhibit increased expression of productive cycle transcripts in ganglia. Ganglia infected with these mutants contained levels of cytokine transcripts similar to those in wild type-infected ganglia; any increases in viral antigen expression mediated by the LAT deletion were not accompanied by increased cytokine expression. Thus, neither viral replication, the ability to reactivate, nor LAT expression in ganglia is required for persistent elevated cytokine expression. The results provide indirect evidence that low-level expression of viral productive cycle genes in neurons can provide signals that elicit cytokine expression.

Animals↗

PubMed1995

Detection of latent varicella zoster virus DNA and human gene sequences in human trigeminal ganglia by in situ amplification combined with in situ hybridization.

Varicella zoster virus (VZV) establishes latency in sensory ganglia following primary infection (chickenpox) and may reactivate decades later to produce zoster (shingles). The presence of VZV DNA in latently infected ganglia has been demonstrated by Southern blot hybridization as well as by polymerase chain reaction of DNA extracted from latently infected ganglia. Conflicting results have been obtained by in situ hybridization studies to determine the cell type in the ganglia harboring the latent VZV. To address this controversy we have utilized a more sensitive method than the previous studies. We have applied the technique of polymerase chain reaction to sections of ganglia from latently infected individuals and combined this with in situ hybridization to detect the amplified product. Primers specific for VZV were used to amplify VZV DNA in latently infected human trigeminal ganglia and demonstrated the presence of VZV DNA in neurons only. Sections from human kidney and ganglia from neonates as well as monkey ganglia served as controls and did not show amplification of VZV sequences. Amplification using primers for human genes, alpha tubulin and the oncogene Bcl-2, demonstrated the presence of these sequences in nearly all cells in the human tissues while only weak signals were seen in the monkey tissue. This is the first report where in situ amplification has been utilized to detect latent VZV in human ganglia.

Base Sequence↗

PubMed1998

Are giant ganglia a reliable marker of intestinal neuronal dysplasia type B (IND B)?

It has been suggested that giant ganglia are a marker for a developmental bowel disorder, intestinal neuronal dysplasia of the submucosal plexus (IND B), diagnosed in a proportion of patients with severe intractable constipation. Diagnosis of this condition, however, remains controversial with a wide variation in the frequency of diagnosis in different centres. Our aim was to assess the frequency with which giant ganglia could be found in the bowel of individuals who did not give a history of life-long constipation. We also aimed to assess the reproducibility of giant ganglia counts. For this two pathologists independently assessed pieces of normal bowel taken away from the site of the lesion in patients who had undergone surgery for colorectal carcinoma. Giant ganglia containing seven or more ganglion cells were found in 76 and 78% of subjects by each of the two pathologists. There was 1 giant ganglion per 10 ganglia counted in those patients in whom they were identified and 1 giant ganglion per 10.9 ganglia overall. Sections from eight patients in whom there was a history of constipation and/or melanosis coli did not show a greater number of giant ganglia. We conclude therefore that so-called "giant ganglia" are a common feature in the submucosa of normal bowel and that the presence of occasional giant ganglia cannot be considered diagnostic of IND B.

Colorectal Neoplasms↗

PubMed1998

Cellular reactions to axotomy in rat superior cervical ganglia includes apoptotic cell death.

The cellular response to axonal injury in the superior cervical ganglion was examined by immunofluorescence at intervals from 6 h to 14 days after transection of the internal and external carotid nerves. GAP-43-immunoreactivity (IR) appeared in some neurons in the ganglia 1 day after axotomy, while neurons in control ganglia were GAP-43 negative. In 3 days axotomized ganglia GAP-43-IR structures were increased in number and intensity in nerve fiber bundles, while GAP-43-positive perikarya were restricted to the middle and caudal parts of the ganglia and showed an intensity that was stronger than at 1 day after axotomy. These GAP-43-positive neurons were also galanin positive. In the cranial part of the ganglia, S100-IR in satellite cells was weak at 18 h after axotomy. Peripheral to this area, S100-IR was stronger and co-localized with HSP-72-IR, preferentially located in satellite cells. HSP-72-IR was, however, occasionally observed also in principal neurons at 1 and 3 days after axotomy. In eosin-stained sections, neurons and satellite cells in the cranial part of 1 day axotomized ganglia were reduced in number, and a further loss was noted at 3 days. At 12 h some satellite cells in the cranial part of the ganglia were labelled by the in situ DNA 3'-end labelling method, indicating apoptosis, and at 18 h many cells were labelled. Some neuronal perikarya were also labelled in this region. Labelling was not observed at 1 day or later after axotomy, nor in control ganglia. The results may imply that not only neurons but also satellite cells react to neuronal axonal injury with apoptosis. Neurons in the middle and caudal part of the ganglia survived and showed increased content of GAP-43 and galanin, possibly a sign of regeneration/neuronal plasticity.

Animals↗

PubMed1984

Inhibition by indomethacin of in vitro reactivation of latent herpes simplex virus type 1 in murine trigeminal ganglia.

Infectious virus could no longer be detected in the trigeminal ganglia removed from mice 25 days after infection with herpes simplex virus type 1 (HSV-1) by the lip route. When the ganglia were cultured in vitro for 1 or 2 days, infectious HSV-1 was again detected in the ganglia, indicating the reactivation of latent HSV-1. The effect of indomethacin on this reactivation was examined. When the ganglia were cultivated in the presence of 5 X 10(-4) M-indomethacin, the appearance of infectious virus in the ganglia was almost completely inhibited. After removal of indomethacin, infectious virus appeared and the virus titre reached levels found in the ganglia cultured in indomethacin-free medium, indicating that the inhibition of the reactivation may not be due to the cytotoxic effect of indomethacin on the ganglionic cells. The inhibitory effect of indomethacin was only seen when it was added shortly after explantation. These results suggest that indomethacin affects some early processes of viral reactivation in the explanted ganglia. The synthesis of prostaglandins (PGE and PGB) found in the explanted ganglia was strongly suppressed by indomethacin, as was the viral reactivation. Other inhibitors of prostaglandin synthesis, i.e. tetracaine, mepacrine and mefenamic acid, also inhibited viral reactivation in the explanted ganglia. These results suggest that the inhibitory effect of indomethacin on the reactivation of latent HSV-1 may be due to the inhibition of prostaglandin synthesis, although it is possible that other cellular changes which could be caused by indomethacin contributed to the suppression of reactivation.

Animals↗