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PubMed2000

Abnormal polarization and axon outgrowth in retinal ganglion cells lacking the POU-domain transcription factor Brn-3b.

The POU domain transcription factor Brn-3b (also called Brn-3.2) is essential for the normal development of retinal ganglion cells (RGCs) in the mouse. Without Brn-3b, RGCs commit to their fate and migrate to the ganglion cell layer, but most cells die during fetal development. An earlier report (L. Gan et al., 1999, Dev. Biol. 210, 469-480) suggested that cell death was caused by abnormal axon formation. Here, we use retinal explants from wild-type and mutant embryos to show that brn-3b-deficient RGCs are not properly polarized and tend to form dendrites rather than axons. Compared with wild-type explants, neurites of RGCs from brn-3b-deficient retinal explants grew slower, were shorter, and did not fasciculate properly. Mutant neurites had more microtubules than wild-type controls, and the arrangement of microtubules and neurofilaments was characteristic of dendrites rather than axons. Neurites from individual mutant RGCs displayed abnormal polarity and had dendrite-like branches extending outward from their main axis. Most mutant RGCs exhibited abnormal migratory behavior, and their neurites labeled intensely with the dendrite marker MAP-2. A small number of mutant RGCs were not migratory, and their neurites were longer and labeled positively for the axon marker tau-1, suggesting that some RGCs were not as severely affected by the absence of Brn-3b as others. Although tau-1 was not observed in most mutant neurites, it did accumulate in mutant cell bodies, implying that the absence of Brn-3b caused a defect in axon transport. Thus, Brn-3b appears to control the activity of genes that function in establishing RGC polarity, and without Brn-3b, RGCs cannot extend normal axons.

Animals↗
PubMed1999

Bidirectional signaling between neurons and glial cells via the F3 neuronal adhesion molecule.

F3, a glycosyl-phosphatidylinositol anchored molecule of the immunoglobulin superfamily, is known to influence axonal growth and fasciculation via multiple interactions of its modular immunoglobulin-like domains. We prepared a Fc chimeric molecule (F3IgFc) to identify a) the phenotype of cells bearing F3Ig receptors, b) the glial-expressed molecules interacting with these domains and, c) to characterize in in vitro models the functional impact of the interactions. We observed a strong binding of F3IgFc coated fluorospheres to astrocytes in neural primary cultures and to C6 astrocytoma cells. In agreement, in extracts of developing mouse brain F3IgFc is able to bind tenascin-R, tenascin-C, and isoforms of the proteoglycan-type protein tyrosine phosphatases z/beta. All these molecules are synthetized by glial cells as an indication that F3 participates in neuron-glia interactions. We showed that C6 glia-expressed PTPz/RPTP beta stimulated neurite outgrowth by cortical and cerebellar neurons whereas preclustered F3IgFc specifically modified the distribution and intensity of phosphotyrosine labeling in these glial cells. We also showed that inhibition of tenascin-R interaction with F3 prevented defasciculation of cerebellar explants which normally display a defasciculated outgrowth of neurites on a growth permissive substrate. These results identify F3, RTPz/RPTP beta, and tenascin-R as potential mediators of a reciprocal exchange of information between glia and neurons.

Animals↗
PubMed1991

Retinal axons in Xenopus show different behaviour patterns on various glial substrates in vitro.

Several lines of evidence suggest that glial cells have major effects on neuronal pathfinding. We have examined in vitro whether the outgrowth pattern of Xenopus retinal fibres is influenced by the glial cells encountered as they grow to the optic tectum. Strips of retina were cultured on monolayers of glial cells from the diencephalon and from the rostral and caudal ends of the optic tectum. On glia from the caudal end of the tectum the growth of fibres from the nasal and temporal ends of the strips was different: temporal fibres were shorter and more fasciculated than nasal fibres. This difference was still discernible on glia isolated from the rostral end of the tectum, but to a lesser extent. On glia from the diencephalon there was no difference between nasal and temporal fibres.

Animals↗
PubMed1996

An ultrastructural study of glomeruli associated with vomeronasal organs transplanted into the rat CNS.

Rat neonate vomeronasal organs were transplanted into the parietal cortex of littermates to examine their survival and the behavior of axon growth into the surrounding host brain parenchyma. After survival times of 10-100 days the brains were processed for ultrastructural examination. The transplanted vomeronasal organs (VNO) formed several vesicles lined with a sensory epithelium. From these sensory epithelia, VNO neurons leave the epithelium and enter the host brain. Transplant neurons grew axons that fasciculated into bundles surrounded by sheath cell processes and formed one or more fiber plexuses containing distinct globose or spherical-shaped glomerular-like structures. The glomeruli consisted of nerve terminals between which existed asymmetric synaptic contacts. Rarely did we observe clear reciprocal synapses. The glomeruli also contained terminals that showed signs of degeneration, such as increased density of the terminals, clumping of mitochondria and multivesicular bodies. The glomeruli were not partitioned or subdivided by glial septa; however, glial profiles were interspersed among the sensory terminals. Transplant glomeruli also lacked periglomerular cells and had no definitive glial envelope. These results suggest that glomerular formation is not dependent on dendrite contribution of second order neurons or glial support, but rather on a complementary population of receptor neurons.

Animals↗
PubMed1993

Anatomical and radiological observations concerning ossification of the sacrotuberous ligament: is there a relation to spinal diffuse idiopathic skeletal hyperostosis (DISH)?

In a collection of 101 anatomical preparations of the human pelvis, ossification of the sacrotuberous ligament was found in 8 cases. In 7 of these, the ossification showed a characteristic intraligamentous morphology, with a broad-based origin at the ischial tuberosity and tapering off craniomedially. The length varied between 1.1 and 7.2 cm. The surface of the bone formations appeared fasciculated, except in one case which had a wax-like flowing bone formation lying upon the sacrotuberous ligament. Careful anatomical and radiological examination of the spine, the ulnae, the calcanei and the iliac crests in these 8 cases, revealed in only one case any findings (spurs at the olecranon) that could be attributed to extraspinal manifestations of diffuse idiopathic skeletal hyperostosis (DISH). Indeed, in no case were the most widely accepted diagnostic criteria of DISH, the spinal alterations, seen. We therefore suggest that ossification of the sacrotuberous ligament is an autonomous finding and not a good indicator of the presence of spinal DISH.

Adult↗
PubMed1992

Neuromyotonia: report of a case.

Neuromyotonia is a rare condition of peripheral nerve dysfunction characterized by the signs of motor nerve hyperactivity, namely, myokymia, fasciculations, and muscular stiffness. Relaxation of voluntary muscle contraction is delayed, and fluid movements are impaired to a variable degree. Signs of sensory involvement are less frequent. Usually, therapy with carbamazepine or phenytoin provides rapid improvement. In the present communication, a typical case is reported, and the most important differential diagnoses are outlined.

Adolescent↗
PubMed1975

On the fine structure of the external glial layer in the isocortex of man.

The surface of the external glial layer of the isocortex in the human temporal lobe is generally slightly undulated, with a few protrusions and indentations. The surface is formed by an uninterrupted basement membrane which is continuous over the surface no matter how tortuous it becomes. The overall thickness of the glial layer is generally 15 to 25 mum, but diminishes to about 5 mum immediately beneath blood vessels. It consists mainly of a variable number of stacked glial cell processes. Two groups of cell bodies are encountered particularly in the middle and lower levels of the glial layer. Most of the cells are specialized fibrous astrocytes. They are characterized by eccentrically placed, rounded nuclei with homogeneously dispersed chromatin, and electron-lucent cytoplasm rich in filaments. Lipofuscin pigment granules occupy large areas of the perikaryon. The astroglial cells give rise to four types of processes: foot-processes, tangential and radial processes, and processes irregular in outline. The foot-processes ascend towards the cortical surface and terminate as flat expansions spreading out immediately beneath the basement membrane. Contiguous terminal expansions are connected by gap junctions. The individual profiles are irregular in form and fit together like in a jig-saw puzzle. The plasmalemma beneath the basement membrane is underlined by a fuzzy material, which is penetrated by glial filaments. In the terminal expansions individual or groups of mitochondria are abundant. The tangential processes are straight and slender and form a lattice within the middle and deep level of the external glial layer. They contain numerous filaments, evenly distributed or fasciculated. The remainder of the lattice is filled up by a considerable number of processes irregular in outline and varying greatly in size. They contain fewer filaments than the tangential processes, coursing in all directions, and glycogen particles. In both types of processes only a few mitochondria are present. These processes are also connected by gap junctions and desmosomes, too. Large cytoplasmic areas of astroglial cells localized in the deepest portion of the glial layer protrude into the neuropil of the molecular layer, giving rise to several radiate processes, which extend deeper into the cortex. The second, heterogeneous group of cell bodies is characterized by elongated nuclei, ovoid or irregular in outline, which are smaller than those of astroglial cells, and contain blocks of condensed chromatin; a thin cytoplasmic rim generating a few appendages surrounds the nucleus. The first sub-type is characterized by a nucleus with large chromatin blocks bordering the inner nuclear membrane and a medium-dense cytoplasmic matrix. The second sub-type displays smaller chromatin condensations at the inner nuclear membrane and many microtubules are scattered throughout an electron-lucent cytoplasm.

Adult↗
PubMed1992

The fascicular organisation of the cat optic nerve.

Mammalian optic nerve axons are organised within a fascicular framework. This pattern changes between the eye and the chiasm. For most of the length of the nerve fascicular patterns are apparent, but close to the chiasm, in a region of major fibre rearrangement, the fascicular configuration is lost. It is not known how this change occurs, or whether there are less obvious systematic changes in the number of fascicles or their geometry along the length of the nerve. In this study these questions have been addressed at successive locations along the length of the cat optic nerve. The number of fascicles varied depending upon the location examined. A relatively high number were found behind the eye. The number declined in the mid-orbital portion before increasing again in the region of the optic canal. Further caudally there was a progressive change in the pattern of fasciculation, with a loss of fascicular structure medially. The remaining fascicles became concentrated around the inferotemporal periphery of the nerve. There was no fascicular organisation at the point at which the two nerves fused at the chiasm. Although the number of fascicles varied along the length of the nerve their geometric pattern did not change.

Animals↗
PubMed1991

Initial stages of retinofugal axon development in the hamster: evidence for two distinct modes of growth.

In order to characterize differences in growth patterns of axons as they elongate toward their targets and during the initial stages of terminal arbor formation within the targets, we examined the primary visual system of fetal and newborn hamsters using three morphological methods: the Cajal-deCastro reduced silver method, the rapid Golgi technique, and anterograde transport of HRP. Axons emerge from the retina between the 10th and 11th embryonic days (E10-E11). The front of retinal axons crosses the chiasm, extends over the primitive dorsal nucleus of the lateral geniculate body (LGBd) by E13, and advances to the back of the superior colliculus (SC) by E13.5-E14. The rate of axon growth during this advance is nearly 2 mm/day. Collateral sprouts appear on axons around E15.5. In the LGBd and SC, these sprouts arise from multiple sites along the parent axons. Only one or a few of the sprouts continue to grow and branch, while others are eliminated. The net rate of axon collateral advance in this second phase is an order of magnitude slower than during the stage of axon elongation. Thus, formation of CNS projections may involve two qualitatively distinct modes of axon growth. The arborization mode contrasts with the elongation mode by the presence of branching, a lack of fasciculation and a slower average rate of extension. The stereotypic direct advance of axons during elongation also differs from the remodelling which occurs during arborization. The delay between axon arrival at targets and onset of arborization could be a reflection of axons "waiting" for a maturational change to occur in the retina or in targets. Arborization in the LGBd and SC is initiated around the same time, implicating the former possibility. However, a slower differentiation of retinal arbors in the SC, in addition to morphological differences of arbors in the two structures, suggests that alterations in substrate factors also play a critical role in triggering the early stages of arbor formation.

Aging↗
PubMed1980

The astrocytes in the retina and optic nerve head of mammals: a special glia for the ganglion cell axons.

The neuroglia in the retina and the intraocular portion of the optic nerve of the monkey and cat has been examined by light and electron microscopy. In the retina two types of macroglial cells can be distinguished: 1) Müller cells, and 2) astrocytes. The bipolar radial glial cells of Müller penetrate the entire thickness of the retina and their basal processes align in the nerve fibre layer to form septa that fasciculate the axons of the ganglion cells. In contrast to the Müller cells, the retinal astrocytes are not homogeneously distributed throughout the retina; their number correlates with the thickness of the nerve fibre layer. The processes of the astrocytes are confined to the ganglion cell layer and to the nerve fibre layer. In the latter, the astrocytic processes run parallel to and between the axons of a given nerve fibre bundle. According to cytological criteria, the retinal astrocytes are protoplasmic. In the intraocular portion of the optic nerve, however, the astrocytes are fibrous and their processes run perpendicular to the axon bundles of the prelaminar portion of the optic nerve. Thus, because of their intimate morphological relationship to axons of the nerve fibre layer and the intraocular portion of the optic nerve, the astrocytes in the eye of the monkey and the cat may be considered as a special glia for the axons of ganglion cells.

Animals↗
PubMed1989

Monensin induces distortion of optic nerve crossing at the chick embryo chiasm.

The effects of intraocular injection of monensin, a specific inhibitor of membrane glycoprotein transport within the axon, on the development of the chick embryo optic nerve were examined. A proportion of axons growing from the monensin-injected eye were misrouted into the opposite optic nerve at the chiasm and grew to the retina of the opposite eye. These results suggest that formation of the decussation pattern at the chiasm primarily depends on neurite fasciculation mediated by membrane glycoproteins.

Animals↗
PubMed1989

Severe neuropathy in a patient with acquired immune deficiency syndrome (AIDS). Evidence for widespread cytomegalovirus infection of peripheral nerve and human immunodeficiency virus-like immunoreactivity of anterior horn cells.

A patient with acquired immune deficiency syndrome (AIDS) developed a progressive neuromuscular disorder which included a sensory component, severe weakness and muscle wasting, and fasciculations. At autopsy, there was evidence of severe peripheral neuropathy, as well as widespread cytomegalovirus (CMV) infection within the central and peripheral nervous system. Although the anterior horn cell complement within the spinal cord appeared normal, there was also evidence of human immunodeficiency virus (HIV)-like immunoreactivity of rare anterior horn cells, as judged by immunohistochemical staining. This patient illustrates the complexity of pathogenetic mechanisms operative in AIDS patients with neuromuscular disease, and suggests that at least some examples of neuromuscular disease in patients with this syndrome may be related to widespread CMV infection of the peripheral nerve (including microvascular endothelial cells) and, more rarely, direct HIV infection of some anterior horn cells.

Acquired Immunodeficiency Syndrome↗
PubMed1981

Adult form of basal cell naevus syndrome: a family study.

A 32-year-old patient had marked reduction of visual acuity due to falciform folds of the retina and retinal detachment, and severe neurological abnormality: bilateral pyramidal involvement, fasciculation in all limbs and gait ataxia. Skull radiographs showed internal frontal hyperostosis; CT scan showed calcification of the falx cerebri, and multiple arachnoid cysts were shown by myelography. A naevoid lesion had previously been removed from the left forearm. There was a history of ophthalmological symptoms in the mother and the daughter of the propositus. His son has "café au lait" spot on the abdomen and dentigerous cysts. The diagnosis of an adult form of basal cell naevus syndrome with an autosomal dominant mode of inheritance is discussed.

Adult↗
PubMed1984

The syndrome of continuous muscle fibre activity following gold therapy.

A 72-year-old man suffering from arthritis received a total dose of 500 mg sodium aurothiomalate during a period of 5 months. His clinical state then deteriorated and he had to be hospitalized. Upon admission he was bedridden, his level of consciousness was slightly impaired, he was confused and respiration was laboured. Continuous muscle activity was noted on all extremities and at first, erroneously, fasciculations were diagnosed. The EMG exhibited continuous muscle fibre activity consisting of duplets, triplets and multiplets. The discharges occurred in an irregular pattern; when various muscles were examined at the same time no synchronicity could be observed between muscle discharges. In the left m. deltoideus an increased percentage of polyphasic potentials was found, whereas mean duration of motor unit potentials was normal. Spontaneous activity remained unchanged during sleep and administration of intravenous diazepam or phenytoin. Blocking of ulnar nerve at either elbow or wrist level did not stop spontaneous activity in m. abductor digiti quinti. Ischaemia increased the amount of discharges after 7 min. Within 4 months after termination of gold therapy the patient's condition improved and he was discharged from hospital. Regular EMG follow-up after 8 months showed complete cessation of abnormal spontaneous activities. Nerve conduction velocities were normal except for markedly reduced compound action potential in peroneal nerves. Continuous muscle fibre activity as a side-effect of gold therapy is described.

Aged↗
PubMed1984

Muscle hypertrophy and a syndrome of continuous motor unit activity in prednisone-responsive Guillain-Barré polyneuropathy.

The clinical, electrophysiological and morphological findings (light and electron microscopy of the sural nerve and gastrocnemius muscle) are reported in an unusual case of Guillain-Barré polyneuropathy with an association of muscle hypertrophy and a syndrome of continuous motor unit activity. Fasciculation, muscle stiffness, cramps, myokymia, impaired muscle relaxation and percussion myotonia, with their electromyographic accompaniments, were abolished by peripheral nerve blocking, carbamazepine, valproic acid or prednisone therapy. Muscle hypertrophy, which was confirmed by morphometric data, diminished 2 months after the beginning of prednisone therapy. Electrophysiological and nerve biopsy findings revealed a mixed process of axonal degeneration and segmental demyelination. Muscle biopsy specimen showed a marked predominance and hypertrophy of type-I fibres and atrophy, especially of type-II fibres.

Electromyography↗
PubMed1985

Amyotrophic lateral sclerosis. A study of its presentation and prognosis.

All identified Israeli patients with amyotrophic lateral sclerosis (ALS) with onset of the disease from 1959 through 1975 (n = 318) were evaluated clinically. Most of our patients (63%) presented with weakness; only 10% presented with atrophy and 3% with fasciculations. In 31% of the cases, the onset of the disease was focal and 22% of the patients presented with bulbar signs, but only 6 patients presented with emotional lability (pseudo-bulbar). Twelve per cent of the patients presented with muscle cramps, pain or paraesthesia. Atypical signs such as motor cranial nerve lesion, dementia, sphincter disturbance and deep sensation loss are discussed. A relatively high proportion of our patients suffered from malignant tumour, but with no association with any specific tumour. The median survival time was 3 years. Patients with onset of their disease with bulbar signs had a shorter life expectancy (2.2 years): Twenty nine per cent of our patients survived for more than 5 years and 16% for more than 10 years.

Adult↗
PubMed1991

Ontogenetic changes in the regenerative ability of chick retinal ganglion cells as revealed by organ explants.

Whereas mature neurons in the central nervous system (CNS) of birds lack the capability of regenerating axons after injury, embryonic nerve cells are able to do so. The time course of this decline of regenerative ability was investigated in ganglion cells from embryonic chick retinae. Retinal strips from 7- to 19-day-old embryos (E7-E19) were explanted and cultured in vitro. The numbers of retinal ganglion cell (RGC) neurites that had extended during the first 22-23 h incubation, their elongation rates, and morphometric parameters of the growth cones were measured to characterize the regenerative behavior. We observed two periods of decline in neuritic growth: the first from E7 to E9, and another from E14 to E19. The first decrease may reflect a gradually disappearing portion of neurons which produced their axons de novo. The second decline coincides with the major period of synaptogenesis by ganglion cell axons in ovo. The time required for initiation of axonal outgrowth increased, accordingly, from less than 3 h in explants from younger retinae (E7-E16) to 10-12 h for E17 and E19 explants. Axonal elongation rates ranged between 36 micron/h and 56 micron/h (mean values) for E7-E13 explants, but were significantly lower for cells from E14-E19 retinae (13-21 microns/h). Morphologically, neurites and growth cones for RGC explanted before E17 were characterized by their high variability. They possessed more filopodia than mature neurons (E17, E19), fasciculated to a higher degree and branched more frequently. In addition, older neurites appeared "stiffer" and were morphologically simpler.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Respiratory and pulmonary haemodynamic changes during experimental organophosphate poisoning in goats.

Five French Alpine goats received 2 mg kg-1 of dichlorvos (DDVP) by intravenous injection and 0.15 mg kg-1 of atropine sulphate 5-10 min later. Ventilatory mechanics, gas exchanges, pulmonary haemodynamics and pulmonary vascular resistance (PVR) were measured before treatment, 5 min after DDVP injection and 5 min after atropine injection. Within 2 min of DDVP administration, all the goats showed acute respiratory distress, excitation and slight muscle fasciculations. A post-inspiratory pause was recorded in 3 goats. Hypersecretion of saliva or nasal discharge was not observed. Dynamic compliance and heart rate decreased significantly and total pulmonary resistance, pulmonary artery and wedge pressures increased significantly. On the other hand, minute ventilation, arterial oxygen and carbon dioxide tensions were not significantly altered by DDVP. Atropine treatment reversed all the clinical and functional parameters, with the exception of the central nervous and muscular signs, which disappeared within 12 h. It was concluded that experimental DDVP toxicosis induced changes in the mechanics of breathing and pulmonary haemodynamics associated with diffuse bronchoconstriction and cardiac insufficiency respectively.

Animals↗