Perineural Sheath Research Articles

Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage

Mutations in the transcription factor SOX10 cause neurocristopathies, including Waardenburg-Hirschsprung syndrome and peripheral neuropathies in humans. This is partly attributed to a requirement for Sox10 in early neural crest for survival, maintenance of pluripotency, and specification to several cell lineages, including peripheral glia. As a consequence, peripheral glia are absent in Sox10-deficient mice. Intriguingly, Sox10 continues to be expressed in these cells after specification. To analyze glial functions after specification, we specifically deleted Sox10 in immature Schwann cells by conditional mutagenesis. Mutant mice died from peripheral neuropathy before the seventh postnatal week. Nerve alterations included a thinned perineurial sheath, increased lipid and collagen deposition, and a dramatically altered cellular composition. Nerve conduction was also grossly aberrant, and neither myelinating nor nonmyelinating Schwann cells formed. Instead, axons of different sizes remained unsorted in large bundles. Schwann cells failed to develop beyond the immature stage and were unable to maintain identity. Thus, our study identifies a novel cause for peripheral neuropathies in patients with SOX10 mutations.

Evaluation of the Optic Nerve Complex in the Orbit Using Coronal Fast Magnetic Resonance Imaging

Recently available coronal fast magnetic resonance imaging (MRI) has very high spatial resolution with good contrast between the optic nerves and cerebrospinal fluid (CSF). The aim of this study was to evaluate the diagnostic value of coronal fast imaging in optic nerve diseases. Thirty-five patients with various Neuro-ophthalmic conditions including 9 with optic neuritis, 6 with optic atrophy, 5 with glaucoma, 4 with segmental optic nerve hypoplasia and 11 with other optic neuropathies including orbital apex syndrome were evaluated with the three-dimensional fast imaging employing steady-state acquisition (FIESTA) sequence in addition to standard MRI protocols. The optic nerve complexes were evaluated on coronal images of the orbits. Detailed demonstration of the optic nerve complex—the optic nerve, the perineural CSF space and dural sheath—could be readily obtained with FIESTA sequence. The acute phase of both optic neuritis and perineuritis showed enlargement of the perineural CSF space; the optic nerve was swollen in optic neuritis but not in perineuritis. Cases of optic atrophy and glaucoma showed perineural CSF space enlargement with normal optic sheath circumference and a thinner optic nerve, while optic nerve hypoplasia showed a smaller dural sheath circumference without perineural CSF space enlargement. In the cases of orbital apex syndrome optic nerve compression by the extraocular muscles was clearly shown. Coronal FIESTA imaging of the orbit is capable of delineating detailed structural changes in the optic nerve complex and is of diagnostic value for the differentiation of optic nerve diseases.

Epithelioid Sarcoma of the Forearm Arising from Perineural Sheath of Median Nerve Mimicking Carpal Tunnel Syndrome

We report here a case of epithelioid sarcoma in the forearm of a 33-year-old male presenting with symptoms and signs of carpal tunnel syndrome originating from the direct involvement of the median nerve. Due to the slow growing of the tumor, the patient noticed the presence of tumor mass in his forearm after several months from the initial onset of the symptoms. Magnetic resonance imaging showed an 8 × 4 cm mass involving the median nerve in the middle part of the forearm, and histological analysis of the biopsy specimen revealed the diagnosis of epithelioid sarcoma. Radical surgical resection was performed in conjunction with adjuvant chemotherapy. The function of the flexors were restored by the multiple tendon transfers (EIP → FDS; ECRL → FDP; BrR → FPL; EDM → opponens) with superficial cutaneous branch of radial nerve transfer to the resected median nerve. The function of the affected hand showed excellent with the DASH disability/symptom score of 22.5, and both the grasp power and sensory of the median nerve area has recovered up to 50% of the normal side. The patient returned to his original vocation and alive with continuous disease free at 3.5-year follow-up since initial treatment.

Microanatomical structure of the human sciatic nerve

Sciatic nerve is the largest peripheral nerve of the human body. It gives motor and sensitive innervation for the most of lower limb. The aim of the present investigation was revealing his fascicular pattern in relation to microanatomic morphometric characteristics of its connective tissue sheaths. The material consisted of sciatic nerve slices, excised from 17 cadavers of humans aging 8-93 years. After routine histologic processing and light microscopic examination of the preparations, morphometric analysis was performed at magnifications of 40 and 630x. Sciatic nerve showed to be polyfascicular nerve type, with the group pattern of nerve fascicless distribution. The number of fascicless ranged from 27 to 70, whereas the number of fascicless per square millimeter was 1-4. Morphometric and correlation analysis confirmed the significant increase of whole sciatic nerve cross section area, which was associated with the significant increase of its epi- and perineural connective tissue sheaths. Interfascicular sciatic nerve domains of elderly persons contained more adipose tissue. Moreover, already detected loss and degeneration of the large myelinated nerve fibers within fascicles was accompanied by the significant increase of endoneural connective tissue. In conclusion, our study revealed comparative connective tissue enlargement of human sciatic nerve in the course of aging. These phenomena might influence on result of injured nerve's surgical reparations. We interpret this finding as non-specific compensatory phenomenon elicited by loss of thickest myelinated nerve fibers, higher vulnerability of remaining ones, and age-dependent decrease of connective tissue elasticity.

Histochemical demonstration of a monocarboxylate transporter in the mouse perineurium with special reference to GLUT1

Peripheral nerves express GLUT1 in both endoneurial blood vessels and the perineurium and utilize glucose as a major energy substrate, as does the brain. However, under conditions of a reduced utilization of glucose, the brain is dependent upon monocarboxylates such as ketone bodies and lactate, being accompanied by an elevated expression of a monocarboxylate transporter (MCT1) in the blood-brain barrier. The present immunohistochemical study aimed to examine the expression of MCT1 in the peripheral nerves of mice. MCT1 immunoreactivity was found in the perineurial sheath and colocalized with GLUT1, while the endoneurial blood vessels expressed GLUT1 only. An intense expression of MCT1 in the perineurium was confirmed by Western blot and in situ hybridization analyses. Ultrastructurally, the MCT1 and GLUT1 immunoreactivities in the thick perineurium showed an intensity gradient decreasing towards the innermost layer. In neonates, the MCT1 immunoreactivity in the perineurium was intense, while the GLUT1 immunoreactivity was faint or absent. These findings suggest that peripheral nerves depend on monocarboxylates as a major energy source and that MCT1 in the perineurium is responsible for the supply of monocarboxylates to nerve fibers and Schwann cells.

Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy

The distribution and fine structure of lymphatic vessels associated with nerves was studied by immunohistochemistry in the murine craniofacial region. The tissue sections and blocks were immunostained for LYVE-1, protein gene product 9.5, CD34 and aquaporin-1 to demonstrate the lymphatic vessels, nerves, blood vessels and water channel protein, respectively. Transmission electron microscopic examination was also performed to investigate the relationship between the lymphatics and nerves. In the nasal area, the lymphatics were found in dura mater on the cribriform plate and beneath the nasal mucosa, this supposedly supplying the cerebrospinal fluid drainage route along the olfactory nerves. The proximal portions of the cranial nerves were equipped with the lymphatics in the epineurium. In the distal portions of the nerves, the lymphatics were distributed in close proximity of the perineural sheath, and thus might contribute to maintenance of microenvironment suitable for the nerves by an absorptive activity of the lymphatic endothelial cells. The present findings suggest that the lymphatic system associated with the cranial nerves provides the pathway for transport of cerebrospinal fluid, tissue fluid, and free cells involved in immune response and tumor metastasis in the craniofacial region.

Fascicular analysis at perineurial level of the branching pattern of the human common peroneal nerve

The macroscopic branching pattern of the peripheral nerves is usually provided by the epineurial connective tissue, whereas the removal of the epineurium discloses component fascicles covered by a perineurial sheath comprising a fine network with a peculiar branching pattern. In order to compare both patterns, the common peroneal nerve (PC) was dissected minutely in 10 human legs. At the epineurial level the branching pattern into tributary bundles was variable in respect to both the origin of the superficial peroneal nerve and that of the muscular branches (Rr. m. peroneus longus, RPL) to the peroneus longus. At the perineurial level the fascicles formed intricate tiny plexuses without a discrete branching pattern, but as a whole consisted of a regular arrangement divided into four crural streams for the deep peroneal (PP), the accessory deep peroneal (PPA) and two dorsal cutaneous nerves. The RPL fascicles were derived substantially from the PPA stream. The findings on the fascicular branching pattern in the present study show that the PC consists of two muscular and two sensory streams that were ensheathed by the epineurium to form the PP containing a single muscular stream, and the superficial peroneal nerve with the three remaining streams. Thus the extensor and peroneal muscles of the leg have their own nerve supply from the PP and PPA, respectively. The branching pattern of the fascicles of muscular branches at the perineurial level may be a useful estimator of muscle grouping, for which the branching pattern at the epineurial level is hardly of any use due to its variability.

Transient Receptor Potential Vanilloid 1 Mediates Hyperalgesia and Is Up-Regulated in Rats With Chronic Pancreatitis

The neurobiologic basis of pancreatic hyperalgesia in chronic pancreatitis (CP) is understood poorly and there is a need to identify novel therapeutic targets. Our aim was to study the role of the transient receptor potential vanilloid 1 (TRPV1), a key integrator of noxious stimuli, in the pathogenesis of pancreatic pain in a rat model of CP. CP was induced in rats by intraductal injection of trinitrobenzene sulfonic acid. TRPV1 currents in pancreas-specific DRG neurons were measured using perforated patch-clamp techniques. Reverse-transcription polymerase chain reaction was used to measure mRNA expression of TRPV1 in these neurons after laser capture microdissection. Immunofluorescence and Western blot analysis, using TRPV1-specific antibodies, also were performed. Pancreatic hyperalgesia was assessed by rat's nocifensive behavior to electrical stimulation of the pancreas. CP was associated with a 4-fold increase in capsaicin-induced current density (P < .02), along with an increase in the proportion of pancreas-specific DRG neurons that responded to capsaicin (52.9% in controls vs 79.0% in CP; P < .05). CP also was associated with a significant increase in TRPV1 expression both at the messenger RNA and protein level in whole thoracic DRGs and pancreas-specific sensory neurons. Systemic administration of the TRPV1 antagonist SB-366791 markedly reduced both visceral pain behavior and referred somatic hyperalgesia in rats with CP, but not in control animals. TRPV1 up-regulation and sensitization is a specific molecular mechanism contributing to hyperalgesia in CP and represents a useful target for treating pancreatic hyperalgesia caused by inflammation.

Perineural Infusion of Local Anesthetics:“More to the Review”

Perineural Infusion of Local Anesthetics:“More to the Review”

Mucocutaneous Neuromas

The spectrum of clinical findings associated with PTEN tumor suppressor gene germline mutations, referred to as PTEN hamartoma-tumor syndrome (PHTS), includes Cowden and Bannayan-Riley-Ruvalcaba syndromes. Although the skin is the ectodermal structure most often affected by these autosomal dominant genodermatoses, abnormalities of neural tissues are frequently observed. We describe a 5-year-old boy with macrocephaly, prominent corneal nerves, and progressive development of multiple painful, dome-shaped, translucent pink to skin-colored papules on the vermilion portion of the upper lip, fingers, palms, and shins. Histologic evaluation demonstrated dermal proliferation of well-demarcated nerve bundles associated with abundant mucin and surrounded by a distinct perineural sheath, findings diagnostic of a nonencapsulated neuroma. Genetic analysis revealed a novel heterozygous germline nonsense mutation in PTEN, predicted to result in a truncated PTEN protein. To our knowledge, this represents the first report of multiple neuromas as the sole mucocutaneous manifestation of PHTS. This article highlights neuromas as a cutaneous sign of PHTS, drawing attention to manifestations of PHTS in neural tissues of the skin, eye, gastrointestinal tract, and brain. Along with multiple endocrine neoplasia type 2B, PHTS should be considered in the differential diagnosis of multiple mucocutaneous neuromas, particularly those involving extrafacial sites.

Laser-Doppler-gestützte Kontrolle der Sympathikolyse nach kontinuierlicher axillärer Plexusanalgesie bei Patienten mit CRPS I

The aim of this study was to evaluate continuous brachial plexus analgesia in terms of pain relief and sympathicolysis in patients suffering from CRPS I. A detailed clinical examination comprised measurement of temperature changes (Infrared Thermometry), pain rating (VAS scale) and assessment of peripheral sympathetic nervous function using laser Doppler flowmetry. A total number of 12 patients (mean age: 56 +/- 9 years, range: 30 to 69 years) received continuous brachial plexus analgesia after placing a catheter in the perineurial sheath of the brachial plexus through an axillary approach. Prior to continuous analgesia (Morphin 0.04 mg/ml, Clonidin 1.5 microg/ml, Bupivacaine 0.0625 %) running at 4 ml/h a test dosis of 20 ml Bupivacaine 0.25 % was applied to establish brachial plexus block. After an equilibration period of 2 hours, consecutive pain measurements revealed sufficient pain relief in 9 out of 12 patients (75 %) with a mean pain rating dropping from 4.7 +/- 0.68 to 1.59 +/- 1.02 (p < 0.001). Pain reduction was accompanied by a significant temperature increase from -0.78 degrees C to 1.7 degrees C (p < 0.05). However measurement of sympathetic function by laser Doppler flowmetry revealed that no significant sympathicolysis occurred. The study shows that clinical investigation of temperature change is not reliable in the evaluation of sympathicolysis. This is of special interest in patients who are suspected of having sympathically maintained pain (SMP) and are treated by brachial plexus analgesia.

Successful Removal of a Knotted Fascia Iliaca Catheter: Principles of Patient Positioning for Peripheral Nerve Catheter Extraction

Peripheral nerve catheters are typically advanced a substantial distance into a perineural sheath, theoretically increasing the risk of catheter knotting and kinking. In this case report, we describe successful removal of a knotted fascia iliaca catheter and discuss principles of nonsurgical catheter extraction. A 64-yr-old woman with bilateral coxarthrosis presented for total hip arthroplasty under combined general/regional anesthesia. A 20-gauge fascia iliaca catheter was inserted before surgery by using a loss-of-resistance "double pop" technique. The catheter was uneventfully advanced 10 cm past the needle tip. After injection of 30 mL of 0.5% bupivacaine with 1:200,000 epinephrine and 100 microg of clonidine, general anesthesia was induced. An infusion of 0.1% bupivacaine at 20 mL/h was initiated in the recovery room for postoperative analgesia. Approximately 48 h later, resistance was encountered during catheter removal. Catheter extraction was attempted by altering patient positioning, including the supine position during which the catheter placement had occurred. Successful catheter removal was achieved by decreasing tension on the fascia lata and fascia iliaca through flexion of the hip joint and by applying firm, steady traction. The catheter was removed intact with a knot approximately 2 cm from the distal tip. We conclude that the principles for removal of entrapped peripheral catheters are not well known and may differ from those for neuraxial catheters. Patient positioning to minimize pressure and tension on the perineural soft tissues may facilitate catheter removal.

Implantation of neural stem cells via cerebrospinal fluid into the injured root.

In avulsion injury of the dorsal root, regenerating axons cannot extend through the entry zone, i.e. the transition zone between peripheral and central nervous systems, due to the discontinuity between Schwann cells and astrocytes. We infused neural stem cells through the 4th ventricle in an attempt to enhance axonal growth in injured dorsal roots. Infused stem cells were attached to, and integrated into, the lesion of the root and became associated with axons in the same manner as Schwann cells or perineurial sheath cells in the peripheral nerve, and as astrocytes in the central nerve area. These findings suggest that neural stem cells integrated by infusion through CSF might have a beneficial effect on nerve regeneration by inducing a continuity of Schwann cells and astrocytes at the transition zone.

Glucose transport in the heart.

The heart is a unique organ in many ways. It consists of specialized muscle cells (cardiomyocytes), which are adapted to contract constantly in a coordinated fashion. This is vital to the survival of the organism given the central role of the heart in the maintenance of the cardiovascular system that delivers oxygen, metabolic substrates and hormones to the rest of the body. In order for the heart to maintain its function it must receive a constant supply of metabolic substrates, to generate ATP to maintain contractile function, without fatigue. Thus the heart is capable of utilizing a variety of metabolic substrates and is able to rapidly adapt its substrate utilization in the face of changes in substrate supply. The major metabolic substrate for the heart is fatty acids. However, up to 30% of myocardial ATP is generated by glucose and lactate, with smaller contributions from ketones and amino acids. Although glucose is not the major metabolic substrate in the heart at rest, there are many circumstances in which it assumes greater importance such as during ischemia, increased workload and pressure overload hypertrophy. Like all other cells, glucose is transported into cardiac myocytes by members of the family of facilitative glucose transporters (GLUTs). In this regard, cardiomyocytes bear many similarities to skeletal muscle, but there are also important differences. For example, the most abundant glucose transporter in the heart is the GLUT4 transporter, in which translocation to the plasma membrane represents an important mechanism by which the net flux of glucose into the cell is regulated. Because cardiomyocytes are constantly contracting it is likely that contraction mediated GLUT4 translocation represents an important mechanism that governs the entry of glucose into the heart. While this is also true in skeletal muscle, because many muscles are often at rest, insulin mediated GLUT4 translocation represents a quantitatively more important mechanism regulating skeletal muscle glucose uptake than is the case in the heart. In contrast to skeletal muscle, where most GLUT1 is in perineural sheaths (1), in the heart there is significant expression of GLUT1 (2), which under certain circumstances is responsible for a significant component of basal cardiac glucose uptake. This review will summarize the current state of knowledge regarding the regulation of glucose transporter expression, and the regulation of glucose transport into myocardial cells.

The human round window – a perilymph pressure regulator?On a novel mechanoreceptor‐like neuron in the human round window membrane

A medial innervation of the human round window membrane (RWM) was recently discovered in well fixed human tissue using immunohistochemistry. In the present study we used re‐embedding and serial thin section ultrastructural techniques (TEM) to locate and follow these nerve fibres from the spiral ganglion (SG) to the RWM. One neuron projecting through a small perforating bone channel into the RWM could be analysed in detail near the lamina spiralis ossea. Within the middle layer of the RWM it formed a terminal ‘loop’ and was anchored in the stromal tissue. The inward projecting fibre was surrounded by a loose perineural sheath interrupted by gaps where basal lamina faced the extra‐cellular matrix, similar to joint mechanoreceptors. Followed proximally, the neuron branched and formed a unit of several myelinated and un‐myelinated nerve fibres. The cell body was traced to the SG and showed unique ultrastructural features seemingly representing a novel type of ganglion cell unlike the small and large cells nor...

Neuroma prevention by end-to-side neurorraphy: an experimental study in rats

Purpose The successful treatment of painful neuromas remains a difficult goal to attain. In this report we explore the feasibility of neuroma prevention by insertion of the proximal end of a nerve through an end-to-side neurorraphy into an adjacent mixed nerve to provide a pathway and target for axons deprived of their end organ. Methods Experiments were performed on a total of twenty 250-g Sprague-Dawley rats. Two groups of 10 animals were prepared. Group A served as an anatomic control. In group B the right saphenous nerve was transected and implanted end-to-side through an epineurial window into the tibial nerve distal to the trifurcation of the sciatic nerve. After 12 weeks the corresponding sensory neurons were identified by retrograde labeling techniques and histomorphometric analysis of the proximal and distal tibial nerve segments, and regular histology of the end-to-side site were performed. Results The results of the retrograde labeling of the corresponding sensory neuron pool of the saphenus nerve showed extensive labelling of the L1 to L3 spinal ganglions after intracutaneuous tracer application of the planta pedis. The morphology of the end-to-side coaptation site and histomorphologic analysis prove that sensory neurons penetrate the perineurial sheath and axons regenerate along the tibial Schwann cell tubes toward their targets. Conclusions Axons of a severed peripheral nerve that are provided with a pathway and target through an end-to-side coaptation will either be pruned or establish some type of end-organ contact so that a neuroma can be prevented. Whether these axons will lead to disturbing sensations such as paresthesia or dysesthesia in the newly found environment or remain silent codwellers, this experiment cannot answer. Long-term results of future clinical work will have to decide whether the prevention of the neuroma through end-to-side coaptation will be an appropriate therapy for this difficult problem.

Effect of various nerve decompression procedures on the functions of distal limbs in streptozotocin-induced diabetic rats: further optimism in diabetic neuropathy.

It is known that diabetic neuropathy is the result of endoneurial edema caused by various biochemical reactions triggered by hyperglycemia. This sequence of events can cause cessation of circulation at the perineurial level, or the tough layer, which is not resilient enough to spread intraneural pressure. Internal and external limiting structures create a double crush phenomenon to the nerve structure. Decompression of the nerve trunk at separate levels is one of the adjuncts to the overall treatment plan for diabetic neuropathy. In this study, the right sciatic nerves of 30 rats with streptozotocin-induced diabetes were used; three groups were created. In the control group, the sciatic nerves were explored and dissected only. In group II, tarsal tunnel release was performed and accompanied by epineurotomy of the sciatic nerve and its peroneal and tibial extensions. In group III, in addition to the procedures performed in group II, perineural sheaths, exposed through the epineurotomy sites at both the peroneal and tibial nerves, were incised for decompression of the fascicles. Improvement in diabetic neuropathy was evaluated by using footprint parameters. The last print length values, estimated according to the 38-month measurements, were 26.1 +/- 0.12 mm in the control group, 23.2 +/- 0.07 mm in group II, and 22.2 +/- 0.1 mm in group III. The toe spread and intermediate toe spread values of the groups were parallel to improvements in print lengths throughout the study. The best improvement was observed in the perineurotomy group. Finally, an electron microscopic study revealed variable degenerative changes in all groups, but they were milder in groups II and III. This experimental study reveals that adding internal decompression to external release doubled the effect in reducing derangement in the sciatic nerves of the rats and, in the authors' opinion, offers cause for further optimism in the treatment of diabetic neuropathy.

Putative neurohemal release zones in the stomatogastric nervous system of decapod crustaceans.

The stomatogastric nervous system (STNS) of decapod crustaceans has long been used to study the modulation of small neural circuits. Profiles in the sheath of the nerves and ganglia of the STNS, which contain only dense-core vesicles, have been described in electron microscopical studies (Friend [1976] Cell Tissue Res. 175:369-380; Kilman and Marder [1997] Soc Neurosci Abstr. 23:477; Skiebe and Ganeshina [2000] J Comp Neurol 420:373-397). These profiles resemble those found in neurohemal organs and suggest the presence of neurohemal release zones in the STNS. To map these putative neurohemal release zones, a combination of two antibodies was used in the present study. A synapsin antibody recognizing vesicle proteins of clear vesicles was combined with a synaptotagmin antibody recognizing vesicle proteins of clear and dense-core vesicles. Exclusive synaptotagmin-like staining, therefore, indicated the regions with only dense-core vesicles. Such a staining was found in a mesh in the perineural sheath of nerves in the STNS of all three species investigated. In the crayfish Cherax destructor and the lobster Homarus americanus, the stained mesh was located in the sheath of nerves connecting all four ganglia of the STNS, whereas in the crab Cancer pagurus it was found on different nerves, which are more directly exposed to the hemolymph in this species. Exclusive synaptotagmin-like staining was also found in a putative neurohemal release zone in the sheath of the circumoesophageal connectives and the postoesophageal commissure in C. destructor. These data suggest that an important source of modulation of the networks and the muscles of the stomach is a compartmentalized release of neurohormones from zones in the STNS.

Allatostatins of the tiger prawn, Penaeus monodon (Crustacea: Penaeidea)

More than 40 peptides belonging to the -Y/FXFGL-NH 2 allatostatin superfamily have been isolated and identified from the central nervous system (CNS) of the tiger prawn, Penaeus monodon (Crustacea: Penaeidea). The peptides can be arranged in seven sub-groups according to the variable post-tyrosyl residue represented by Ala, Gly, Ser, Thr, Asn, Asp, and Glu. Two of the residues (Thr and Glu) have not been observed in this position previously in either insects or crustaceans. Also reported for the first time for allatostatins, two of the peptides are N-terminally blocked by a pyroglutamic acid residue. The yields of certain peptides with similar amino acid sequences to each other were, in some instances, very different. As an example, the yield of ANQYTFGL-NH 2 was 2 pmol, compared with ASQYTFGL-NH 2, with a yield of 156 pmol. There are several possibilities to account for this. If, as in all species so far investigated, there is a single allatostatin gene in P. monodon, then it would appear that different sub-populations have contributed mutant forms of particular peptides to the extract. Another, less likely possibility is that this species has more than one allatostatin gene, producing a variable array of peptides albeit in different molar ratios. Several peptides were present apparently as a result of the loss of one or more residues at the N-terminus of a larger form, either due to N-terminal degradation or specific post-translational processing. The number of peptides identified exceeds that for any other insect or crustacean species previously investigated. None is identical to any of the 60–70 insect allatostatins so far identified, and only three are common to other crustaceans. Immunohistochemical study of the CNS of P. monodon, with the same antisera as used to monitor the purification, confirms the widespread nature and complexity of allatostatinergic neural pathways in arthropods. Thus, all neuromeres of the brain, and all except one of the ventral cord ganglia, possess allatostatin neurons and extensive areas of allatostatin-innervated neuropile. In addition to the cytological evidence that the allatostatins act as neurotransmitters, associated with tissues as varied as eyes and legs, their presence in neurohemal areas such as the sinus gland and the perineural sheath of the thoracic ganglia suggests a neuroendocrine function. As well as posing a challenge to physiologists assigning specific functions to the allatostatins, their extensive intra-species multiplicity, linked to their inter-species variability, also presents a complex problem to geneticists and evolutionists.

Molecular cell biology of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT), also named hereditary motor and sensory neuropathies, includes a clinically and genetically heterogeneous group of disorders affecting the peripheral nervous system. Traditionally, the different classes of CMT have been divided into demyelinating forms (CMT1, CMT3, and CMT4) and axonal forms (CMT2), a clinically very useful distinction. However, investigations of the underlying molecular and cellular disease mechanisms, mainly accomplished using cell culture and animal models, as well as specific re-examination of appropriate patient cohorts, have revealed that the pathological signs of myelinopathies and axonopathies are often intermingled. These findings, although only recently fully appreciated, are not surprising given the dependence and intimate cellular interactions of Schwann cells and neurons, mainly during nerve development and, as indicated by the pathology of CMT, also in the adult organism. This review is intended to summarize our current knowledge about the molecular and cellular basis of CMT, with a particular emphasis on the role of Schwann cell/axon interactions. Such a view is particularly timely since approximately ten genes have now been identified as culprits in different forms of CMT. This collection revealed novel crucial players in the interplay between Schwann cells and neurons. The analysis of these genes and their encoded proteins will provide additional insights into the molecular and cellular basis of neuropathies and valuable information about the biology and interactions of Schwann cells, their associated neurons, endoneurial fibroblasts, and the nerve-surrounding and protecting perineurial sheath.