Schwann Cell Nuclei Research Articles

Abnormalities expressed in long-term cultures of dorsal root ganglia from the dystrophic mouse

We have compared the development in long-term tissue culture of dorsal root ganglia taken from normal and dystrophic mice. Cultures were prepared from late fetal (15--20 days) or neonatal mice of either the C57BL/6 dy2j/dy2j dystrophic (dy) or C57BL/6J +/+ (control) strain and maintained until fully myelinated (5 weeks or more). Analysis by light and electron microscopy indicated that the substantial ensheathment failure present in certain dy nerve roots in vivo is not expressed in cultures; myelination and Schwann cell numbers are comparable to control cultures. On the other hand, many of the subtle abnormalities more recently described in distal parts of peripheral nerves of dystrophic mice are expressed in the dy cultures. These include: (a) discontinuity in the basal lamina surrounding both myelin-forming and non-myelinating Schwann cells: (b) elongated nodes of Ranvier occurring along otherwise well myelinated nerve fibers; (c) relatively short myelin internodes that are increased in thickness as well as irregularities of internode length along a nerve fiber; (d) Schwann cell nuclei substantially displaced from the central point of myelin internodes; and (e) occasional regions of incomplete ensheathment of unmyelinated nerve fibers. In discussing these observations, we present arguments that the dy nerve lesion may be explained by the presence of an abnormality in the extracellular matrix of the peripheral nerve tissues of the dy mouse.

Nerve xenografts to apportion the role of axon and Schwann cell in myelinated fiber absence in hereditary sensory neuropathy, type II

Sural nerve fascicles from two patients with a recessively inherited sensory neuropathy—hereditary sensory neuropathy type II (HSN II) with complete absence of myelinated fibers—were grafted into the left sciatic nerves of 30 nude mice. Nerve fascicles from age-matched healthy control subjects were grafted into the right sciatic nerves of the same mice. At 6 months, abundant myelinated fibers were found in the 10 disease xenografts studied—by visual microscopic examination not different from the paired control xenografts. The number of myelinated fibers, the size distribution of diameters of myelinated fibers, the slope and intercept of linear regression of number of myelin lamellae on area of axis cylinders of myelinated fibers, number of endoneurial nuclei (mostly Schwann cells) per cubic millimeter, and labeling indices of Schwann cell nuclei (with the use of [³H]-thymidine) did not significantly differ in disease and control xenografts. These studies indicate that the Schwann cells of HSN II can myelinate mouse axons. The absence of myelinated fibers in sensory nerves of HSN II is therefore due to an axonal abnormality—possibly a failure of development or degeneration in utero. The studies further indicate that grafted Schwann nerves of patients with cells from only unmyelinated fibers are the likely source of cells that ensheath and myelinate regenerating mouse axons. This provides further suggestive evidence for the role of axons in determining whether Schwann cells become differentiated into cells forming myelin of myelinated fibers or cells forming sheath cells of unmyelinated fibers.

Development of the amyelinated lesion in the ventral root of the dystrophic mouse: Ultrastructural, quantitative and autoradiographic study

Postnatal development of the L5 ventral spinal root was studied in dystrophic (Bar Harbor 129 ReJ dy/dy) and normal mice by ultrastructural, quantitative and autoradiographic methods. Ultrastructural studies of normal roots showed that at birth most axons were invested with Schwann cell cytoplasm, while in dystrophic roots there were large groups of amyelinated fibres. By the 4th day, the normal animal had no naked axons, while large groups of amyelinated fibres remained in the dystrophic animals. Further abnormalities present in the ventral roots of dystrophic mice, both at birth and on the 4th day, included the presence of Schwann cells not committed to any axons, and deficiency of the Schwann cell basement membrane. Quantitative studies showed that at birth the number of myelinated fibres in dystrophic roots was 34% of normal, and remained constant throughout life, while in normals there was a 10-fold increase within 15 days. The number of dystrophic Schwann cell nuclei per whole L5 root transverse section, when corrected for nuclear and root length, was 76% of normal at birth, 20% 15 days later and 50% in adults. The rate of proliferation of dystrophic Schwann cells (labelling index) was normal at birth (dystrophic 8%, control 8.4%), fell to 2.2% in dystrophics and 4.7% in controls at 7 days, and in adults was 0.4% in dystrophics and < 0.1% in controls. It was calculated that even at the observed slower rate of proliferation, the Schwann cell population of the dystrophic L5 ventral root could have risen to that of the normal root by about the 12th postnatal day. It is suggested that in the dystrophic L5 ventral root from birth to 3 weeks of age the Schwann cell production is balanced by an equivalent cell loss.

Schwann cell multiplication deficit in nerve roots of newborn dystrophic mice: A radioautographic and ultrastructural study

Neonatal Schwann cell development was studied in mice with genetic muscular dystrophy (dy 2J/dy 2J) to investigate the pathogenesis of the bare axonal segments which characterize certain spinal roots and peripheral nerves in these animals. From the day of birth to 3 weeks of age, dystrophic and control animals were injected with tritiated thymidine 1 hr prior to sacrifice. Cross-sections of their L4 ventral roots and sciatic nerves were processed for radioautography. Labelled and unlabelled Schwann cell nuclei, as well as numbers of myelinated fibres, were counted by phase microscopy and the same nerves examined by electron microscopy. On the day of birth, groups of large naked axons were present in the roots of dystrophic animals while in control roots most axons were isolated by Schwann cells or their processes. The number of myelinated fibres increased rapidly between days 1 and 9 in control roots but failed to increase in the dystrophic roots. On day 2, Schwann cell labelling indices were significantly lower in dystrophic roots than controls but were similar in dystrophic and control sciatic nerves. Many Schwann cells in the dystrophic roots did not encircle axons. It is concluded that the Schwann cell deficit in dystrophic mice is a developmental abnormality present at birth and associated with a neonatal impairment of Schwann cell multiplication. The presence of this unique abnormality of Schwann cell proliferation suggests an impairment of the mechanisms involved in the control of axon and Schwann cell populations during development.

Experimental necrosis and arrest of proliferation of Schwann cells by cytosine arabinoside.

In developing rat cervical sympathetic trunks, Schwann cells proliferate intensely during the first week after birth but axonal populations do not increase. Thus, experimental inhibition of DNA synthesis should affect Schwann cells and spare axons whose cell bodies are not dividing. The present investigation was aimed at determining the effects of an inhibitor of DNA synthesis-cytosine arabinoside (ara-C)--on axons and Schwann cells in developing nerves. Ara-C (60 mg kg(-1) body weight) was injected subcutaneously to newborn rats every six hours for 36 hours. At intervals from 2--4 days of age, animals were given tritiated thymidine (4 muCi per gram body weight) to label Schwann cells in synthesis phase. One hour later rats were killed by systemic perfusion of phosphate buffered glutaraldehyde. Cervical sympathetic trunks (CST's) and sciatic nerves were removed and processed for radioautography and electron microscopy (EM). Labelled and unlabelled Schwann cell nuclei were counted to determine the labelling index (LI%) for each nerve. By the end of ara-C treatment there was almost complete absence of labelling but LI's rose sharply 24 hours after discontinuing ara-C. By EM axons appeared normal; Schwann cells, however, showed prominent nuclear and cytoplasmic changes consisting of nuclear degeneration, dilatation of rough endoplasmic reticulum and increased cytoplasmic density. Ara-C, by suppressing proliferation and causing necrosis of Schwann cells but sparing axons, results in a developmental alteration of axon-Schwann cell relationships. It is suggested that the pathogenetic mechanism involves an inbalance in DNA/RNA synthesis metabolism.

Schwann cell internuclear distances in developing rat unmyelinated nerve fibers.

The interrelation of Schwann cells in developing rat cervical sympathetic trunk was studied by measuring distances between consecutive Schwann cell nuclei in teased unmyelinated nerve fiber bundles (Remak fibers). From 300 to 400 inter-nuclear Schwann cell distances (INDs) were measured at ten days and 2, 4, 5, 6, 8, 12, and 16 weeks after birth. Median INDs increased from 54mum at ten days to reach adult values (90mum to 100mum) at 16 weeks of age. Mean axonal diameters measured in the contralateral cervical sympathetic trunk increased from 0.57mum to 0.69mum during the same period. Developmental changes in median INDs of Schwann cells correlated significantly with age but did not parallel increases in axonal diameter.

UNMYELINATED FIBRES AND SCHWANN CELLS OF SURAL NERVE IN NEUROPATHY

Electron micrographs of 45 sural nerves from patients with acquired (22) or heredodegenerative neuropathy (23) were analysed with respect to the number of unmyelinated nerve fibres, 37 nerves with respect to the number of Schwann cell sub-units and of structures connected with Schwann cells. Findings were compared with those in 6 nerves from control subjects and referred to the total number rather than to the number per mm2 to eliminate error due to increase in the transverse endoneurial area, present in more than half the diseased nerves. Ninety-one per cent of the diseased nerves showed one or several abnormalities in unmyelinated fibres of their Schwann cells. The best indicator of fibre loss was an increase in the number of Schwann cell sub-units devoid of axons, found in more than half the nerves. This was the only abnormality related with decrease in number of myelinated fibres. The increase in number of empty Schwann cell sub-units was due both to loss of unmyelinated nerve fibres and to proliferation of Schwann cells. Proliferation was indicated by the higher incidence of Schwann cell nuclei in cross-sections of diseased nerves than in controls. The earliest sign of involvement was an increase in number of profiles and of small isolated Schwann cell projections, observed in 33 of 37 diseased nerves, as the only abnormality in 7 nerves. The number of unmyelinated nerve fibres by itself was of little value to indicate loss of fibres, since regeneration often replaced or more than replaced degenerated fibres. Regeneration was indicated by an increase in number or incidence of small unmyelinated fibres, present in nearly half of 45 diseased nerves; and by an increased in the total number, present in a third of the nerves. An increase in the number of collagen pockets and of fibres undergoing degeneration (loss of organelles) and a decrease in the number of unmyelinated fibres per Schwann cell sub-units was present in only a quarter to a third of diseased nerves and was not related to other criteria of loss of fibres or of regneration.

Ultrastructural study of the human utricular macula and vestibular nerve in meniére's disease.

The authors have carried out an ultrastructural study of the human utricular macula and the vestibular nerve in the internal acoustic meatus of four patients suffering from Meniere's disease. They confirm the presence of degenerative alterations in the utricular sensory epithelium. The nervous fibers situated in the supporting connective tissue of the neuro-epithelium showed modifications in the Schwann cell cytoplasm and in the arrangement of the myelin sheaths. The same alterations appear in the vestibular nerve in the internal acoustic meatus in 2 of our cases. In the other 2, the vestibular nerve was formed by a granular matrix with several myelin figures in the proximity of possible Schwann cell nucleus debris.

Ribosomes in myelinated axons of dorsal root ganglia.

In the dorsal root ganglia of the rat, ribosomes were found not only in the initial segment, but they were also observed in the axoplasm of intraganglionar myelinated fibres and in the sensory portion of spinal nerves. Axons of seven-days-old rats contained more ribosomes than those of adult animals. The amount of particles decreased gradually from the initial segment trough intraganglionar internodes to the axons of spinal nerves. No ribosomes were found in axons of dorsal roots. In intraganglionar fibres, ribosomal particles were usually observed near the nodes of Ranvier, in the vicinity of Schmidt-Lantermann clefts and in axons near the Schwann cell nuclei. They were arranged in tetrads, pentads or in larger polysomes, and they were often observed adjacent to a group of mitochondria. The particles had invariably a stable size, their average diameters measuring 234 ± 2 × 197 ± 3 A, which is practically equal to the diameters of 232 ± 2 × 203 ± 3 A of ribosomes in the Schwann cell cytoplasm. These values fall within the range of diameters of ribosomes isolated from various cells of eukaryotic organisms as given in the literature. Since no other granular component of the cytoplasm has similarly stable dimensions, the measurements are considered to prove that the axonal particles described here are ribosomes.

Die Nerven der Papilla filiformis der Zunge vom Meerschweinchen

Peripheral nerve fasciculi, supplying filiform papillae, are composed of unmyelinated and a few myelinated axons. The nerve fibers are surrounded by an one-layered perineural sheath and run, in parallel to the capillary loops, towards the tip of the papilla. Myelinated axons devide and lose their myelin sheath, and somewhat later their perineurium ends. Unmyelinated axons show striking swellings caused by an accumulation of mitochondria. These structures are believed to represent the receptive sites (presumably thermo- or mechano-receptors) of nerves. Fine unmyelinated fibers enter the epithelium. Schwann cell nuclei, surrounded by large cytoplasmic areas occur near the epithelium.

Synthesis of nucleic acids in the Schwann cells as the early cellular response to nerve injury.

Abstract— The early effect of mechanical injury of the sciatic nerve in cats and rats on the amount of nucleic acids and on the number of Schwann cells was studied.The content of RNA and DNA increased at both ends of a severed nerve as early as 2 hr after operation; at 8 hr and up to 24 hr, their level was about twice as high as at the beginning of experiment. The increase in nucleic acids seemed to be chiefly due to their biosynthesis in the Schwann cells although the possibility of a contribution of axonal RNA must also be taken into consideration. The division of Schwann cell nuclei was observed not earlier than 36 hr after operation. The injury stimulates the synthesis of nucleic acids not only in the Schwann cells directly damaged, but also in those from neighbouring internodes.The increase in DNA and RNA observed 24 hr after a fresh lesion had been made in a degenerating nerve was smaller than the increase observed 24 hr after cutting or crushing a normal nerve.

Cellular kinetics of the peripheral nerve and striated muscle after a single dose of x-rays. A histological and autoradiographical study, using 3H-thymidine.

Thirtysix mice were irradiated with a single dose of X-rays (2760 rad) on one leg, while the rest of the body was shielded by lead. The animals were killed 1–270 days after the irradiation and 3H-thymidine was injected 2 hours before death. Sections from the sciatic nerve and its innervated muscles were examined by autoradiography and by special methods for the mast cells. No changes in the endoneurial mast-cell component could be disclosed after irradiation. At all times after the irradiation, the numbers of labelled Schwanncell nuclei and the sarcolemna-cell nuclei were moderately decreased on the irradiated side, when compared with the control side.

Morphogenesis of the Schwann channels in the squid nerve

In the unmyelinated giant fiber of the squid, ∼60 A wide slit channels crossing the Schwann layer were previously described. The present study deals with the morphogenesis of these channels. It was carried out on the nerve fiber of the squid Doryteuthis plei. The fibers were fixed in either osmium tetroxide or potassium permanganate and were embedded in either methacrylate or Araldite. The observation of the whole contour of cross sections of the nerve fibers have shown the existence of as many as eight Schwann cell nuclei. The nonsyncytial nature of the Schwann cell is demonstrated. The Schwann cells appear imbricated and form a layer one cell thick. The existence of cytoplasmic islets surrounded by unit membranes in the Schwann layer are considered to be sections of fingerlike processes of the Schwann cell surface. The digitations might belong to a single Schwann cell or to two or more cells whose processes interdigitate. The apposition of neighboring Schwann cells or of the islets give origin to the channels. The findings here summarized support the extracellular nature of the Schwann channel lumina whose function has been thoroughly explored.

The fine structure of Schwann cells, nodes of Ranvier and Schmidt-Lanterman incisures in the central nervous system of the crab, Cancer irroratus

Electron microscopy of ultrathin sections of crab brain reveals the location of the Schwann cell nucleus outside of the myelin of the nerve fibers, as it is in vertebrate nerves. Comparison of the fine structure of the crustacean and vertebrate nodes of Ranvier reveals an essential similarity. Schmidt-Lanterman incisures, comparable to those of vertebrates, also occur in crustacea. These observations are interpreted as indicating that the myelinated nerves of Cancer irroratus, a crustacean, are quite similar in structure to those of vertebrates. The evolutionary implications of these observations are discussed.