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Development of spiral ganglion cells in mammalian cochlea.

The development of the spiral ganglion in the cat, the rat, and the mouse was studied by electron microscopy, from fetal stages in the cat and from birth in the rodent. In the earliest stages, a single population of ganglion cells is present. Immature spiral ganglion neurons possess small perisomatic processes that seem to disappear with development, before the myelination ganglion cells are surrounded by one or two layers of Schwann cell processes. With maturation, the Schwann process increases in number around the perikaryon and its processes, which leads to the onset of myelination. The onset of myelination of the cell body processes is asynchronous. The perikaryon may be delayed in myelination by several days. Moreover, ganglion neurons from a given region of the cochlea do not myelinate simultaneously. The differentiation of two types of fibers in the intraganglionic spiral bundle and the first appearance of TII neurons occurs around birth in the cat and a few days after birth for the rat and the mouse. The distinction of TII cells is possible due to characteristic accumulation of neurofilamentous structures in the cytoplasm.

Animals↗

Intradermal doxorubicin reduces ganglionic reactivation of latent herpes simplex virus in mice after pretreatment with hypertonic saline.

Recurrent lesions from herpes simplex virus (HSV) occur after reactivation of latent HSV in neurons of sensory ganglion, axonal transport of reactivated virus, and HSV replication on the skin. A potential treatment strategy is to inject epithelial sites of frequent recurrences with anti-viral or cytotoxic agents that are taken up by nerve terminals and transported by axoplasmic flow to latently infected ganglionic neurons. Doxorubicin is transported by nerves and destroys the corresponding nerve cell bodies, but earlier attempts in HSV animal models required intraneural injection to eliminate HSV infection and this treatment destroyed the nerve and large portions of the ganglion. The present study used intradermal doxorubicin in latently infected mice that had been inoculated with HSV by the lip route and passively immunized at the time of inoculation. As found previously, doxorubicin injection in the lip 2 or more months after HSV inoculation did not eliminate HSV latency as evaluated by recovery of virus from trigeminal ganglionic explants. However, when hypertonic saline was injected in the same site 24 hr prior to doxorubicin, there was a 55% reduction of positive ganglionic explant cultures. Edema from the hypertonic saline may increase access of doxorubicin to nerve terminals. This technique with hypertonic saline, which has also been used to enhance virulence of HSV skin innoculation, may have general application of increasing axoplasmic transport of drugs or biologicals. Skin toxicity may preclude doxorubicin use for HSV recurrences in patients; however, the results of this study support the concept of anti-HSV treatment via retrograde axoplasmic transport.

Administration, Cutaneous↗

Formation of the retinal ganglion cell and optic fiber layers.

The early development of retinal ganglion cell and the optic fiber layers has been studied by examining the morphology of differentiating retinal ganglion cells using immunoelectron microscopy and a monoclonal antibody against neuron-specific beta-tubulin. This antibody identified retinal ganglion cells during the stages of their most active differentiation and axonogenesis prior to maturation of other retinal neurons. The changing morphology of retinal ganglion cells during these early stages is consistent with a differentiation sequence in which axonogenesis and translocation of the cell body to the vitreal surface occur while the cell is still attached to the vitreal margin through its vitreal endfeet. Thus, the mechanism of retinal ganglion cell axon generation and soma migration to the vitreal surface appears to involve maintenance of this attachment which may act as both a focus for axon differentiation and an anchor for directed nuclear translocation to the vitreal margin.

Animals↗

Remodeling of retinal ganglion cell dendrites in the absence of action potential activity.

The dendrites of ganglion cells in the retina have an excess number of spines and branches that are normally lost during the first postnatal month of development. We investigated whether this dendritic remodeling can be prevented when the action potential activity of ganglion cells is abolished by chronic intraocular injections of tetrodotoxin (TTX) during the first 4 or 5 postnatal weeks in the cat. Dendritic tree morphologies of alpha and beta ganglion cells from TTX-treated, non-TTX-treated (contralateral eye), and normal control retinae were compared after intracellular filling with Lucifer yellow. Qualitative observations and quantitative measurements indicate that TTX treatment does not prevent the normally occurring loss of spines and dendritic branches. Indeed, the dendritic trees of both alpha and beta cells in TTX injected eyes actually have even fewer spines and branches than normal cells at equivalent ages. However, because the total dendritic lengths of these cells are also reduced after TTX blockade, spine density is indistinguishable from untreated animals at the same age. In addition, although dendritic field areas are not altered with treatment, the complexity of the dendritic trees is reduced. These observations suggest that dendritic remodeling can occur in the absence of ganglion cell action potential activity. Thus, the factors that influence the dendritic and axonal development of retinal ganglion cells must differ, because similar TTX treatment during the period of axonal remodeling does have profound effects on the final pattern of terminal arborizations.

Action Potentials↗

Monoamine oxidase-A-positive retinal ganglion cells projecting to the superior colliculus and dorsolateral geniculate nucleus of the rat brain.

Detailed morphology and distribution of monoamine oxidase type A (MAO-A) positive retinal ganglion cells, and their synaptic terminals in the superior colliculus and the lateral geniculate nucleus, were investigated by light and electron microscopy. In addition, the differences in various retinal ganglion cells with respect to the projection site were examined by the injection of colloidal gold into the superior colliculus and the lateral geniculate nucleus. The effects of unilateral enucleation were also examined. In the retina, small, medium and large sized MAO-A-positive ganglion cells were observed; the large sized cells were distributed evenly throughout the retina, while the small and medium sized cells were most numerous in a ring surrounding the central retina and decreased in density near the optic disc and the peripheral retina. The MAO-A-positive terminals in the superior colliculus were smaller in size than those in the lateral geniculate nucleus. From colloidal gold injection, it was apparent that the MAO-A-positive ganglion cells projecting to the superior colliculus were generally smaller in size than those projecting to the lateral geniculate nucleus. Fourteen days after unilateral enucleation, the MAO-A-positive terminals in the superior colliculus and lateral geniculate nucleus contralateral to the enucleated eye had almost disappeared, whereas those in the ipsilateral regions remained unaffected. These findings demonstrate the distribution and projections of the MAO-A-positive ganglion cells.

Animals↗

Neuropeptide Y expression in the trigeminal ganglion and mandibular division of the trigeminal nerve after inferior alveolar nerve axotomy in young rats.

Neuropeptide Y (NPY) is a 36-amino-acid peptide residing in sympathetic nerve terminals, originating from the superior cervical ganglion in oral tissues. NPY exerts vasoconstrictor action together with noradrenalin and has been found to inhibit the release of neurotransmitters from primary afferent fibers. During regeneration of the axotomized inferior alveolar nerve (IAN), NPY-immunoreactive (IR) nerve fibers have been shown in the odontoblast layer and dentin, an area normally innervated by afferent nerve fibers. The dynamic shift in neuropeptide expression in the trigeminal ganglion and in the dental pulp was studied by immunohistochemistry 1, 2, 3, and 8 weeks after IAN axotomy. In the ipsilateral first mandibular molar a temporal loss of pulpal sensory nerves lasting for approximately 1 week was found after axotomy. An upregulation of NPY was shown in neurons located in the mandibular area of the trigeminal ganglion, concomitant to a reduction in number of neurons expressing substance P (SP). To study an alternate and possible trigeminal origin of some of the peripheral nerve fibers IR to NPY in the dental pulp, double immunofluorescence labeling was performed for NPY and calcitonin gene-related peptide (CGRP). Coexistence of NPY and CGRP was shown in neurons located in the trigeminal ganglion and in nerve fibers in the tooth pulp during IAN regeneration. Furthermore, retrograde tracing with Fluorogold revealed NPY-IR neurons projecting to the first molar pulp 3 weeks after axotomy. Hence, we conclude that after IAN axotomy NPY is produced in trigeminal ganglion neurons and transported in afferent regenerating fibers to the dental pulp. These results add further evidence for a plasticity in peptide transcription in sensory neurons after nerve injury and indicate a trigeminal origin of at least some of the pulpal NPY-IR fibers during nerve regeneration.

Age Factors↗

Expression of sodium channel SNS/PN3 and ankyrin(G) mRNAs in the trigeminal ganglion after inferior alveolar nerve injury in the rat.

The inferior alveolar nerve is a sensory branch of the trigeminal nerve that is frequently damaged, and such nerve injuries can give rise to persistent paraesthesia and dysaesthesia. The mechanisms behind neuropathic pain following nerve injury is poorly understood. However, remodeling of voltage-gated sodium channels in the neuronal membrane has been proposed as one possible mechanism behind injury-induced ectopic hyperexcitability. The TTX-resistant sodium channel SNS/PN3 has been implicated in the development of neuropathic pain after spinal nerve injury. We here study the effect of chronic axotomy of the inferior alveolar nerve on the expression of SNS/PN3 mRNA in trigeminal sensory neurons. The organization of sodium channels in the neuronal membrane is maintained by binding to ankyrin, which help link the sodium channel to the membrane skeleton. Ankyrin(G), which colocalizes with sodium channels in the initial segments and nodes of Ranvier, and is necessary for normal neuronal sodium channel function, could be essential in the reorganization of the axonal membrane after nerve injury. For this reason, we here study the expression of ankyrin(G) in the trigeminal ganglion and the localization of ankyrin(G) protein in the inferior alveolar nerve after injury. We show that SNS/PN3 mRNA is down-regulated in small-sized trigeminal ganglion neurons following inferior alveolar nerve injury but that, in contrast to the persistent loss of SNS/PN3 mRNA seen in dorsal root ganglion neurons following sciatic nerve injury, the levels of SNS/PN3 mRNA appear to normalize within a few weeks. We further show that the expression of ankyrin(G) mRNA also is downregulated after nerve lesion and that these changes persist for at least 13 weeks. This decrease in the ankyrin(G) mRNA expression could play a role in the reorganization of sodium channels within the damaged nerve. The changes in the levels of SNS/PN3 mRNA in the trigeminal ganglion, which follow the time course for hyperexcitability of trigeminal ganglion neurons after inferior alveolar nerve injury, may contribute to the inappropriate firing associated with sensory dysfunction in the orofacial region.

Animals↗

Displaced retinal ganglion cells in normal frogs and those with regenerated optic nerves.

We have analysed the number and spatial distribution of displaced retinal ganglion cells in the frog Litoria (Hyla) moorei. A series of normal animals was compared with one in which the optic nerve was crushed and allowed to regenerate. Ganglion cells were labelled with horseradish peroxidase (HRP) applied to the optic nerve, and retinae were examined as sections or whole mounts. We analysed separately ganglion cells with somata displaced to the inner nuclear (Dogiel cells, DGCs) and to the inner plexiform layer (IPLGCs). These findings were related to data for the orthotopic ganglion cells (OGCs). The mean number of DGCs in the normal series was 2,550 (+/- 281) and fell to 1,630 (+/- 321) after regeneration, representing a mean loss of 36%. This reduction was not significantly different from the mean loss of 43% from the OGC population in which mean values fell from 474,700 (+/- 47,136) to 268,700 (+/- 54,395). In both the normal and the regenerate series, DGCs were estimated to represent means of only 0.6% of the OGC population. Densities of DGCs were highest in the naso-ventral and temporo-dorsal peripheries; densities of both DGCs and OGCs were lower after optic nerve regeneration. We conclude that the factors which affect ganglion cell death during optic nerve regeneration, do so to similar extents amongst the DGC and the OGC populations. The IPLGCs were very rare in normal animals with a mean of 420 (+/- 95). However, their numbers increased after regeneration to a mean of 3,350 (+/- 690), estimated to be 1.2% of the OGC population. These cells normally favoured peripheral retina but became pan-retinal after regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Correlation of neuronal size and peptide immunoreactivity in the guinea-pig trigeminal ganglion.

Frequency and size of guinea-pig trigeminal neurones immunoreactive with antisera to alpha-neo-endorphin-(alpha-neo-END), dynorphin A- (DYN), vasoactive intestinal polypeptide- (VIP), somatostatin- (SOM), and substance P- (SP) are reported. Co-localisation of the various peptides to the same ganglion cells was investigated immunocytochemically in consecutive 7-micron thick paraffin sections. According to their size, all peptide-immunoreactive neurones belong to the class of "small" ganglion cells. Within this cell group, SP-immunoreactive neurones appear to be the largest, followed by SOM-, VIP-, alpha-neo-END- and DYN-immunoreactive ganglion cells. The observed differences in size are statistically significant with the exception of that between alpha-neo-END and DYN. This finding correlates well with the observed co-occurrence of the two immunoreactive peptides. All alpha-neo-END-immunoreactive perikarya are also reactive to VIP antisera. These neurons are significantly smaller than those containing VIP-immunoreactivity exclusively. Ganglion cells displaying co-existence of alpha-neo-END- and SP-immunoreactivity or VIP- and SP-immunoreactivity are found too infrequently to allow morphometric analysis. Some non-immunoreactive ganglion cells are shown to be approached by dense baskets of VIP-, alpha-neo-END- or SP-immunoreactive varicose fibres, indicating the presence of intraganglionic modulation sites. The combination of immunohistochemistry and morphometry presented in this study allows the differentiation of diverse populations of primary afferent neurones exhibiting peptide immunoreactivity, most likely reflecting their involvement in different central and peripheral reflex arcs and sensory modalities.

Animals↗

A qualitative and quantitative analysis of the response of the retinal ganglion cell soma after stretch injury to the adult guinea-pig optic nerve.

The development of a model for focal axonal injury in the optic nerve of the adult guinea-pig has allowed a qualitative and quantitative analysis of the response of the retinal ganglion cell soma to this type of injury. Large and medium sized retinal ganglion cells show classic 'central chromatolysis' in about 30% of ganglion cells between three and seven days after injury, a high proportion of which undergo degeneration between seven and 14 days. Small ganglion cells and small neurons do not demonstrate any morphological response to stretch injury of the optic nerve. However, a small number of larger ganglion cells demonstrate enlargement of the cell soma and nucleolus together with reconstitution of the rough endoplasmic reticulum between seven and 14 days after stretch injury. We suggest that these cells are either recovering from or regenerating after a non-disruptive lesion to their axons. We suggest that some of these morphological changes parallel documented regenerative responses in peripheral/extrinsic neurons after injury to their axons. We conclude that the time course of the 'axon reaction' after stretch injury to axons is longer than that obtained after crush or transection. We provide good morphological evidence that the level of injury after application of non-disruptive mechanical strain to axons is less severe than in the former two models of axonal injury and that a proportion of damaged neurons do not die but rather demonstrate either/or recovery or a regenerative response.

Animals↗

Effects of prenatal cocaine exposure in the retinal ganglion cell layer of the rat. A morphometric analysis.

To study the effects of prenatal cocaine-exposure on the developing retinal ganglion cell layer of the rat, female Wistar rats were administered subcutaneously (sc) cocaine hydrochloride (60 mg/kg body wt/d) or saline, or were not manipulated from gestational d 8-22. Male offspring were sacrificed at postnatal day 14 and 30. Radial semithin sections of epon-embedded flat mounts of the retinal quadrants were used to evaluate the following parameters along the centroperipheral axis: 1. Thickness of ganglion cells plus nerve fiber layer; 2. Nuclear size of ganglion cell layer neurons; and 3. Linear density (number per unit length) of ganglion cell layer neurons. To study the effects of cocaine and age on the retinal areas (temporal/nasal, dorsal/ventral), a repeated measures analysis of variance was used for each of the parameters mentioned above. All parameters were affected by prenatal exposure to cocaine. The thickness of the ganglion cell plus nerve fiber layer was reduced in cocaine-exposed rats in comparison with the saline group. Nuclear diameters were smaller in the cocaine than in the saline and control groups. The linear density was higher in the cocaine-exposed group than in the control and saline groups. The age-dependent decrease in the linear density from postnatal day 14-30 was higher in the cocaine-exposed rats than in the saline group; the decrease in the linear density along the centroperipheral axis found in both the control and saline groups was not significant in the cocaine-treated group. These morphometric findings strongly support the view that prenatal cocaine-exposure induces marked changes in the organization of the developing retina.

Aging↗

Synaptic inhibitory effects of edrophonium on sympathetic ganglionic transmission.

PURPOSE: To evaluate the effect of edrophonium on synaptic transmission in the superior cervical ganglion. METHODS: In anaesthetized rats the effect of edrophonium on synaptic transmission was studied in vitro by testing whether it blocks the compound action potential recorded from postganglionic fibres evoked by stimulation of preganglionic axons. The superior cervical ganglion was excised and the cervical sympathetic trunk and internal carotid nerve were used for stimulating and recording, respectively. Drugs superfused included edrophonium (0.1-500 microM), neostigmine (0.1-10 microM), and muscarinic M1 and M2 antagonists pirenzepine and AFDX-116 (200 nM-10 microM), respectively. To evaluate a presynaptic action, the effect of edrophonium on basal and high-K+ (35 mM) evoked release of [3H]ACh from the superior cervical ganglion was studied in vitro. To evaluate a postsynaptic action, edrophonium's effect on postganglionic nerve discharge in response to arterial injection of ACh (100 micrograms) into the superior cervical ganglion was determined in vivo. RESULTS: Edrophonium (10-500 microM) decreased the compound action potential amplitude (ED50 163.5 microM). A decrease was not produced by neostigmine, nor was it reversed by pirenzepine or AFDX-116. Edrophonium blocked postganglionic cell firing in response to exogenously administered ACh. Although edrophonium did not affect basal or high-K+ evoked ACh release, when the evoked increase was calculated as a multiple of the basal release, it caused approximately a 30% (P < 0.005) reduction. CONCLUSIONS: Edrophonium blocks ganglionic cholinergic transmission postsynaptically and, possibly, presynaptically. The mechanism(s) by which this occurs does not appear to involve inhibition of cholinesterase, or activation of M1 or M2 receptor subtypes.

Acetylcholinesterase↗

Transneuronal retrograde degeneration of retinal ganglion cells following restricted lesions of striate cortex in the monkey.

Transneuronal retrograde degeneration of retinal ganglion cells follows extensive striate cortical removal in macaque monkeys. Its extent depends on the age of the monkey at operation, post-operative survival, species and retinal eccentricity. Some studies of human patients with occipital lobe injury have found no evidence for transneuronal retrograde degeneration, suggesting that either degeneration may not occur or, if present, it is caused directly by secondary damage impinging upon the underlying white matter or the blood supply to the dorsal lateral geniculate nucleus and optic tract. We therefore studied retinal ganglion cell degeneration in three macaques in which only the striate cortex corresponding to the macular retina had been removed, thereby sparing extrastriate cortex and precluding interruption of the vascular supply to the thalamus and optic tract. There was extensive loss of ganglion cells in the central retina, corresponding to the central 10 degrees of vision. As the cortical lesion was too small to affect the thalamus or optic tract directly, the retinal degeneration must be transneuronal. Quantitative analysis showed a 65-80% loss of ganglion cells in the corresponding perifoveal retinae along the horizontal meridian. The results confirm that the loss of retinal ganglion cells following striate cortical lesions is predominantly transneuronal.

Animals↗

Coexisting secondary intraneural and vascular adventitial ganglion cysts of joint origin: a causal rather than a coincidental relationship supporting an articular theory.

OBJECTIVE: To introduce the clinical entity of an intraneural ganglion cyst coexisting with a vascular adventitial cyst arising from the same joint. DESIGN: Retrospective review. PATIENTS: Two patients presented with predominantly deep peroneal neuropathy due to complex superior tibiofibular joint-related cysts. In addition to having peroneal intraneural ganglion cysts, these patients had vascular adventitial cysts: one involving a capsular arterial branch, the other a capsular vein [as well as a large, recurrent, intramuscular (extraneural) ganglion]. We then reviewed MRIs of 12 other consecutive cases of intraneural ganglia (10 peroneal and 2 tibial) arising from the superior tibiofibular joint that we treated, as well as other reported cases in the literature to determine if there were other (unrecognized) examples supporting the combination of clinical findings and radiographic patterns. RESULTS: Retrospective analysis of MRIs in the two surgically proven cases of peroneal intraneural ganglia with vascular adventitial cyst extension showed a common imaging pattern that we have termed "the wishbone sign," consisting of the connection of the ascending limb of the peroneal intraneural ganglion and the longitudinal limb of the vascular adventitial cyst in the axial plane. Our review suggests that vascular adventitial cyst extension occurs in a large proportion of cases of peroneal intraneural ganglia. A similar growth pattern was noted in a case of a tibial intraneural ganglion. CONCLUSIONS: The combination of intraneural and vascular adventitial cysts is understandable given our knowledge of normal and pathologic anatomy of para-articular cysts. The combination of intraneural ganglia and vascular adventitial cysts broadens the spectrum of clinical presentations of these cysts and suggests that cysts and their content can dissect from a joint along neurovascular bundles. These cases provide important evidence to support the articular theory for the pathogenesis of not only neural but vascular adventitial cysts as well.

Diagnosis, Differential↗

Extra-articular soft tissue ganglion cyst around the knee: focus on the associated findings.

The aim of this study was to evaluate MR imaging findings of the associated findings in surrounding tissues of the extra-articular soft tissue ganglion cysts around the knee. We retrospectively reviewed MR images of 30 patients who had surgically confirmed extra-articular soft tissue ganglion cysts around the knee with focus on the associated findings in surrounding tissues, such as muscle, subcutaneous fat, bone, and nerve. The most common associated finding was the visualization of channel between ganglion cyst and the joint, which was demonstrated in 20 cases (continuous type in 12 cases and discontinuous type in 8 cases). Other associated findings were seen in 15 cases; pericystic edema ( n=9), bony remodelling ( n=3), and nerve involvement ( n=3). The bony remodelling involved the proximal metaphysis of tibia in all 3 cases. Two patients with nerve involvement had deep peroneal nerve in subacute phase and one involved common peroneal nerve in chronic phase. The MR imaging is a useful imaging modality to evaluate the associated findings in extra-articular soft tissue ganglion cysts around the knee. The evaluation of these associated findings is helpful for the differentiation of ganglion cysts from other cystic lesions around the knee.

Adolescent↗

Estimate of size and total number of neurons in superior cervical ganglion of rat, capybara and horse.

The superior (cranial) cervical ganglion was investigated by light microscopy in adult rats, capybaras (Hydrochaeris hydrochaeris) and horses. The ganglia were vascularly perfused, embedded in resin and cut into semi-thin sections. An unbiased stereological procedure (disector method) was used to estimate ganglion neuron size, total number of ganglion neurons, neuronal density. The volume of the ganglion was 0.5 mm3 in rats, 226 mm3 in capybaras and 412 mm3 in horses. The total number of neurons per ganglion was 18,800, 1,520,000 and 3,390,000 and the number of neurons per cubic millimetre was 36,700, 7,000 and 8,250 in rats, capybaras and horses, respectively. The average neuronal size (area of the largest sectional profile of a neuron) was 358, 982 and 800 microm2, and the percentage of volume occupied by neurons was 33, 21 and 17% in rats, capybaras and horses, respectively. When comparing the three species (average body weight: 200 g, 40 kg and 200 kg), most of the neuronal quantitative parameters change in line with the variation of body weight. However, the average neuronal size in the capybara deviates from this pattern in being larger than that of in the horse. The rat presented great interindividual variability in all the neuronal parameters. From the data in the literature and our new findings in the capybara and horse, we conclude that some correlations exist between average size of neurons and body size and between total number of neurons and body size. However, these correlations are only approximate and are based on averaged parameters for large populations of neurons: they are less likely to be valid if one considers a single quantitative parameter. Several quantitative features of the nervous tissue have to be taken into account together, rather than individually, when evolutionary trends related to size are considered.

Animals↗

The perikaryal surface of spinal ganglion neurons: differences between domains in contact with satellite cells and in contact with the extracellular matrix.

The perikaryal surface of spinal ganglion neurons undergoes dynamic changes throughout life. In particular, numerous slender projections develop and retract continuously from this surface. We showed previously that the outgrowth of these projections, while an intrinsic property of spinal ganglion neurons, is also influenced by the surrounding microenvironment. Since the latter consists of satellite cells and the extracellular matrix, we sought to determine the relative contributions of each of these components to the outgrowth of perikaryal projections. To this end, we took advantage of a little known characteristic of the satellite cell sheaths: in the rabbit, these sheaths can exhibit gaps that leave the nerve cell body surface directly exposed to the extracellular matrix. We compared the surface domains covered by satellite cells with those in direct contact with the extracellular matrix. We found that the perikaryal projections are abundant in the former domains but are absent in the latter. We also found that the perineuronal extracellular matrix of rabbit spinal ganglia contains laminin and fibronectin, two glycoproteins that have been reported to promote the growth of axonal processes from sensory ganglion neurons. Laminin and fibronectin were also present at the level of the gaps in the satellite cell sheath. These results: (1) provide additional evidence that environmental factors influence the outgrowth of perikaryal projections from spinal ganglion neurons; (2) suggest that satellite cells permit the outgrowth of these projections; (3) suggest that in the spinal ganglia of adult rabbits the perineuronal extracellular matrix is not in itself able to promote the outgrowth of these projections. This study provides a further example of the influence that supporting neuroglial cells have on sensory ganglion neurons.

Animals↗

Expression of the cystine-glutamate exchanger (xc-) in retinal ganglion cells and regulation by nitric oxide and oxidative stress.

The cystine-glutamate exchanger, system x(c)(-), mediates the Na(+)-independent exchange of cystine into cells, coupled to the efflux of intracellular glutamate. System x(c)(-) plays a critical role in glutathione homeostasis. Early studies of brain suggested that system x(c)(-) was present primarily in astrocytes but not neurons. More recent work indicates that certain brain neurons have an active system x(c)(-). In the retina, system x(c)(-) has been demonstrated in Müller and retinal pigment epithelial cells. We have recently suggested that two protein components of system x(c)(-), xCT and 4F2hc, are present in ganglion cells of the intact retina. Here, we have used (1) molecular and immunohistochemical assays to determine whether system x(c)(-) is present in primary ganglion cells isolated from neonatal mouse retinas and (2) functional assays to determine whether its activity is regulated by oxidative stress in a retinal ganglion cell line (RGC-5). Primary mouse ganglion cells and RGC-5 cells express xCT and 4F2hc. RGC-5 cells take up [(3)H]glutamate in the absence of Na(+), and this uptake is blocked by known substrates of system x(c)(-) (glutamate, cysteine, cystine, quisqualic acid). Treatment of RGC-5 cells with NO and reactive oxygen species donors leads to increased activity of system x(c)(-) associated with an increase in the maximal velocity of the transporter with no significant change in the substrate affinity. This is the first report of system x(c)(-) in primary retinal ganglion cells and RGC-5 cells. Oxidative stress upregulates this transport system in RGC-5 cells, and the process is associated with an increase in xCT mRNA and protein but no change in 4F2hc mRNA or protein.

Amino Acid Transport System y+↗