Axon caliber related to neurofilaments and microtubules in sciatic nerve fibers of rats and mice

Abstract

The number of neurofilaments and microtubules present in nerve fibers was determined for sciatic nerves from adult mice and from rats of three different ages. More microtubules than neurofilaments were found in nonmyelinated fibers; the ratio of tubules/filaments was reversed in myelinated fibers and was found to change with axon caliber independent of the presence of a myelin sheath. A series of regression analyses indicated that axon caliber correlates best with the sum of the number of neurofilaments and microtubules per fiber. This correlation was only slightly better than that for neurofilaments alone. Axon caliber also correlated better with the filament-tubular material than with the thickness of the myelin sheath. The results were similar for both rats and mice, and age differences were not apparent in the samples of nerves analyzed.Microtubules are present in the cytoplasm of most cell types during interphase, and they may occur in great number during cell division and under a variety of experimental and pathologic conditions (Bloom and Fawcett, '68). These structures may play a major role in influencing cell shape by imparting a rigidity to various regions of the cell (Tilney, '65; Porter, '66; Tilney and Porter, '69). Recent studies have associated microtubules with the mechanism of cytoplasmic movements in simple organisms and in cultures of nervous system tissues (Allen, '64). It has been suggested, also, that the presence of microtubules and neurofilaments in neurons may in some way be related to the flow of protein in and out of neuronal processes (Weiss and Holland, '67; Ochs, Sabri and Johnson, '69; Sjostrand and Karlsson, '69; Karlsson and Sjostrand, '69).Previous studies from our laboratory have emphasized the importance of axon caliber in controlling myelin sheath thickness during growth of peripheral nerve fibers (Friede and Samorajski, '67, '68; Samorajski and Friede, '68b). Because of the possible participation of neurofilaments and microtubules in growth and axoplasmic transport, the concentration of these structures in relation to axon caliber might be of considerable importance. The present study was undertaken in an effort ANAT. REC., 167: 379-388.to relate filament and tubule concentration with axon caliber in sciatic nerves from young and adult rats and mice. MATERIALS AND METHODSThree adult mice, and 3 rats, 6 and 12 days old and 1 adult, were used for the morphologic comparisons of microtubuleneurofilament density in the fibers of sciatic nerves, In addition, osmotically shocked sciatic nerves from four adult rats were included for comparative purposes.For the first study, the animals were anesthetized with Nembutal (30 mg/kg, I.P.) and both sciatic nerves were exposed and covered with cold 4% glutaraldehyde in 0.2 M cacodylate buffer, pH 7.2, After preliminary fixation in situ for approximately ten minutes, small segments of the nerve were excised and placed in fixative for an additional ten hours at 4°C. After a rinse in buffer, the tissues were placed in cacodylate buffer...

Organelles in Neuroplasmic (“Axonal”) Flow: Neurofilaments

“…Similarly, comparisons between varying neurofilament-to-neurotubule ratios (16) suffer from the disparity of the lumped categories; yet the qualitative conclusion that the number of neurotubules is stabilized early in development, whereas the population of filaments keeps mounting with the growing caliber of the axonal matrix, is well in accord with our data. On the other hand, an earlier suggestion (17), ascribing to the interfaces between neurofilaments and matrix a guiding function in molecular transport, is now ruled out by the instability and discontinuity of the presumed communication lines. This work was performed in collaboration with Yvonne Grott, to whom-we extend our thanks.…”

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

“…126 The CSF level of NF-L correlates with the degree of white matter changes in the brain. 127 CSF-NFL is therefore suggested to be a biomarker for degeneration of large myelinated axons.…”

Axotomy-induced changes in rabbit hindlimb nerves and the effects of chronic electrical stimulation

“…There is good evidence that nerve fiber caliber is correlated with the axonal content of NF protein, with a decrease in caliber occurring with a decline in NF protein after axotomy (Friede and Samorajski, 1970;Hoffman et al, 1987). Alterations in gene expression for NF are seen very soon after axotomy (within 12 hr), and a reduction in protein synthesis in the cell body is already evident a day after axotomy (Hoffman et al, 1987;Wong and Oblinger, 1987;Greenberg and Lasek, 1988;Tetzlaff et al, 1988aTetzlaff et al, ,b, 1989.…”