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Membrane flow within the myelin sheath in IDPN neuropathy
A E Blaurock1, M B Genter St Clair, D G Graham
1Department of Physiology, Duke University Medical Center, Durham, North Carolina.
Abstract:
This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer.
Insights
Beta,beta'-iminodipropionitrile (IDPN) causes significant axon swelling in rat spinal roots. Myelin structure remains intact, suggesting a fluid membrane model for myelin during neuropathy.
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- Beta,beta'-iminodipropionitrile (IDPN) is a neurotoxin known to induce neuropathy.
- Understanding the ultrastructural changes in myelin during neuropathy is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the ultrastructural changes in axons and myelin sheaths during IDPN-induced neuropathy in rats.
- To elucidate the structural dynamics of myelin membranes under pathological conditions.
Main Methods:
- Light microscopy was used to assess axon swelling in spinal roots.
- X-ray diffraction was employed to analyze myelin membrane structure and packing under physiological conditions.
- Ultrastructural methods were applied to examine both central nervous system (CNS) and peripheral nervous system (PNS) myelin.
Main Results:
- IDPN injection led to a substantial increase in axon cross-sectional area (280%) and perimeter (160%) in spinal roots.
- Myelin membrane packing, lipid bilayer thickness, and inter-bilayer aqueous spaces remained unchanged.
- Similar observations were noted in posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin).
Conclusions:
- The findings support a fluid myelin membrane model, where the membrane can flow during axon swelling while maintaining structural integrity.
- Normal membrane-membrane contacts within the myelin sheath are preserved despite significant axon diameter changes.
- A molecular model is proposed to explain membrane flow and slippage within the multilayered myelin sheath.
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