engleski

Functional defects in peripheral nerves from transgenic mice with hyperexpression of heavy neurofilament.

Neurofilaments (NFs; made by co-polymerization of three intermediate filament proteins NF-L, NF-M, and NF-H,for light, medium and heavy) constitute the most abundant cytoskeletal structure in large myelinated axons. Presence of aberrant NF accumulation has been associated with neurodegenerative diseases (such as ALS). The possible casual role of NF in neurodegeneration has been supported by recently available transgenic mice in which hyperexpression of human NF-H (hNF-H +/+) leads to overt neuropathy. To examine electrophysiological properties of myelinated axons in hNF-H +/+ mice. Intra-axonal microelectrode recording from isolated sciatic and tibial nerves. Transgenic mice showed several deficits in physiological properties of low threshold myelinated fibres: conduction velocity (CV) and resting membrane potential were significanty decreased (20-1.6 m/s vs. 40-2m/s; -71.3-99 vs. -75.5- 5m/s; m-SE; n=25; 22 C).While the amplitude of action potentials (AP) were of comparable size (82- 5 vs. 86 - 3 mV) duration of AP (at half amplitude, AP/2) in hNF-H +/+ was significantly prolonged (82- 02 vs. 65- 02 ms). Voltage- current properties of axonal membrane indicate a significant decreas in inward and outward rectification. Occasionally, impaled axons of hNF-H +/+ showed membrane oscillations and repetitive activity (reminiscent of fasciculations) never observed in normal animals. These results are compatible with an imbalance between ion conductanes in axons from transgenic animals (an increase in Na* and a decrease in K* conductances), in agreement with recent clinical studies on ALS patients. One may hypothesize that these changes could contribute to neurodegenerative processed, as well as clinical symptorns opserved in patients with degenerative motoneuron diseases.

nije evidentirano

nije evidentirano