Schwann cells: origins and role in axonal maintenance and regeneration.

The Schwann cell plays a vital role in maintaining the peripheral nervous system (PNS). Schwann cells are derived from neural crest cells, and come in two types either myelinating or non-myelinating Schwann cells. Both play a pivotal role in the maintenance and regeneration of axons of the neurons in the PNS. The regulation of Schwann cells is mediated a number of different neurotrophic factors which signal to transcription factors such as Krox-20, Oct-6 and Sox-10. Schwann cells are affected in a number of demyelinating disorders, such as Charcot-Marie-Tooth disease and Guillain-Barré Syndrome, infected by Mycobacterium leprae to cause leprosy and are responsible for the tumors seen in patients with neurofibromatosis type 1 and neurofibromatosis type 2. The Schwann cell is under investigation as a therapeutic agent for demyelinating diseases and spinal cord injuries. Further research on Schwann cells will help understand these diseases and perhaps lead to new treatments.

It's all in the assay: a new model for retinotectal topographic mapping.

Ephrin-As have been implicated as topographic mapping labels in the retinotectal system, but the underlying molecular mechanisms for their activities in this context remain somewhat mysterious. Hansen et al. (this issue of Neuron) developed an assay that reveals new mechanisms for ephrins in topographic mapping and suggest a model whereby retinal axons grow and terminate in the tectum via a balance of growth promotion and repulsion, with the balance point depending on retinal position and concentration of ephrin-As.

Do nerve growth factor-related mechanisms contribute to loss of cutaneous nociception in leprosy?

While sensory loss in leprosy skin is the consequence of invasion by M. leprae of Schwann cells related to unmyelinated fibres, early loss of cutaneous pain sensation, even in the presence of nerve fibres and inflammation, is a hallmark of leprosy, and requires explanation. In normal skin, nerve growth factor (NGF) is produced by basal keratinocytes, and acts via its high affinity receptor (trk A) on nociceptor nerve fibres to increase their sensitivity, particularly in inflammation. We have therefore studied NGF- and trk A-like immunoreactivity in affected skin and mirror-site clinically-unaffected skin from patients with leprosy, and compared these with non-leprosy, control skin, following quantitative sensory testing at each site. Sensory tests were within normal limits in clinically-unaffected leprosy skin, but markedly abnormal in affected skin. Sub-epidermal PGP 9.5- and trk A- positive nerve fibres were reduced only in affected leprosy skin, with fewer fibres contacting keratinocytes. However, NGF-immunoreactivity in basal keratinocytes, and intra-epidermal PGP 9.5-positive nerve fibres, were reduced in both sites compared to non-leprosy controls, as were nerve fibres positive for the sensory neurone specific sodium channel SNS/PN3, which is regulated by NGF, and may mediate inflammation-induced hypersensitivity. Keratinocyte trk A expression (which mediates an autocrine role for NGF) was increased in clinically affected and unaffected skin, suggesting a compensatory mechanism secondary to reduced NGF secretion at both sites. We conclude that decreased NGF- and SNS/PN3-immunoreactivity, and loss of intra-epidermal innervation, may be found without sensory loss on quantitative testing in clinically-unaffected skin in leprosy; this appears to be a sub-clinical change, and may explain the lack of cutaneous pain with inflammation. Sensory loss occurred with reduced sub-epidermal nerve fibres in affected skin, but these still showed trk A-staining, suggesting NGF treatment may restore pain sensation.

[Lepromatous leprosy: clinical and electrophysiological arguments in favor of axonal multi-neuritis]. / Lèpre lépromateuse: arguments cliniques et électrophysiologiques en faveur d'une multinévrite axonale.

UNLABELLED: This work was undertaken because there were only few reports on neurological aspects on lepromatous leprosy. We studied 30 patients suffering from lepromatous leprosy who, at their first visit to the Institute had never been treated. The clinical examination included a quantitative evaluation of the neurological status following the method developed by Pearson. Motor and sensory nerve conduction velocities were measured: values of conduction velocity and distal amplitude were analysed and compared to those of a group of 22 healthy subjects. IN CONCLUSION: (a) There is a high frequency of clinical and especially electrophysiological neurological impairment. This impairment can be extremely precocious and may happen shortly after the first cutaneous signs. (b) Nervous impairment is diffuse, bilateral but not homogeneous. These are characteristics of mononeuritis multiplex. Impairement is predominantly sensitive and tactile sensibility is more involved than thermo-algic sensation. (c) The radial superficial nerve is the most frequently involved clinically and electrophysiologically. (d) The electrophysiological results, showing a normal or slightly reduced conduction velocity and a low amplitude of evoked potentiel are in favour of a predominantly axonal damage.