Elovl5 is required for proper action potential conduction along peripheral myelinated fibers

ABSTRACT:Background:Machado-Joseph disease (MJD) is a dominantly inherited cerebellar ataxia associated with spasticity, ophthalmoplegia and dystonia. There has been no report of electrophysiological or histological alterations of the peripheral nervous system in patients with MJD.Methods:Four patients with MJD were identified by polymerase chain reaction. The peripheral nerves of these patients were subjected to electrophysiological testing and histological study. Correlation analyses were made between various clinical parameters and the electrophysiological and histological changes.Results:Electrophysiological studies demonstrated a marked reduction of sensory action potential, acute denervation changes on needle EMG, as well as mild decrease in the compound motor action potential. Light microscopy of the sural nerves revealed clear loss of myelinated fibers, and morphometry studies showed a loss of large myelinated fibers. Moreover, the severity of these pathological changes was found to be related to the CAG repeat length in the MJD gene.Conclusion:Our findings indicated that the peripheral nervous system was frequently affected in patients with MJD. These findings were similar to those seen in Friedreich's ataxia, suggesting a loss of sensory and motor fibers probably following a lesion of the dorsal root ganglion and the anterior horns in the spinal cord. Furthermore, the number of CAG repeats seems to have an inverse relationship to the extent of pathological changes of the peripheral nerves.

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Maturation of mammalian myelinated fibers: changes in action-potential characteristics following 4-aminopyridine application

Journal of Neurophysiology ◽

10.1152/jn.1983.50.2.449 ◽

1983 ◽

Vol 50 (2) ◽

pp. 449-463 ◽

Cited By ~ 81

Author(s):

J. D. Kocsis ◽

J. A. Ruiz ◽

S. G. Waxman

Keyword(s):

Action Potential ◽

Myelinated Fibers

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How to sample the entire length of a single muscle fiber quick-frozen after electrical point stimulation for high resolution EM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124288 ◽

1992 ◽

Vol 50 (1) ◽

pp. 776-777

Author(s):

Joachim R. Sommer ◽

Teresa High ◽

Betty Scherer ◽

Isaiah Taylor ◽

Rashid Nassar

Keyword(s):

Skeletal Muscle ◽

High Resolution ◽

Action Potential ◽

Muscle Fiber ◽

Freeze Fracture ◽

Freeze Substitution ◽

Electrical Field Stimulation ◽

Skeletal Muscle Fiber ◽

Freeze Dried ◽

Quick Freezing

We have developed a model that allows the quick-freezing at known time intervals following electrical field stimulation of a single, intact frog skeletal muscle fiber isolated by sharp dissection. The preparation is used for studying high resolution morphology by freeze-substitution and freeze-fracture and for electron probe x-ray microanlysis of sudden calcium displacement from intracellular stores in freeze-dried cryosections, all in the same fiber. We now show the feasibility and instrumentation of new methodology for stimulating a single, intact skeletal muscle fiber at a point resulting in the propagation of an action potential, followed by quick-freezing with sub-millisecond temporal resolution after electrical stimulation, followed by multiple sampling of the frozen muscle fiber for freeze-substitution, freeze-fracture (not shown) and cryosectionmg. This model, at once serving as its own control and obviating consideration of variances between different fibers, frogs etc., is useful to investigate structural and topochemical alterations occurring in the wake of an action potential.

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