Neurofilaments are spaced randomly in the radial dimension of axons

Price, Robert L.; Paggi, Paola; Lasek, Raymond J.; Katz, Michael J.

doi:10.1007/bf01735377

Cited by 76 publications

(58 citation statements)

References 17 publications

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“…Although modest differences in axonal NF density (,'025 %) have been reported among different populations of neurons (Price et al, 1988) and in different regions of small-caliber nerve fibers (Nixon and Logvinenko, 1986;Parhad et al, 1987), greater variations of NF density are not normally observed. The alterations in axonal NF content associated with somatofugal axonal atrophy (where NF content decreases) and with normal postnatal development (where NF content increases) correlate with changes in axonal cross-sectional area, rather than changes in NF density (Friede and Samorajski, 1970;Hoffman et al, 1984;Hoffman et al, 1985).…”

Section: Discussionmentioning

confidence: 93%

Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber.

Monteiro

Hoffman

Gearhart

et al. 1990

The Journal of Cell Biology

160

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Abstract. We have generated transgenic mice containing additional copies of the murine NF-L gene in order to examine the consequences of neurofilament-L overexpression on axonal morphology. Founder mice were constructed to carry a transgene in which the presumptive 5' promoter sequences of NF-L were replaced with the strong murine sarcoma virus long terminal repeat promoter. The transgenes were expressed prominently in several tissues, including skeletal muscle and kidney where NF-L accumulated to ,,02% of cell protein. This was not accompanied by an overt phenotype, except that expression in lens led to cataract formation. In the brains of these animals, transgene RNA levels exceeded the endogenous NF-L RNAs by up to 20-fold, although no additional protein accumulated, indicating posttranscriptional regulation of NF-L expression. However, in peripheral neurons transgene RNA was approximately fourfold higher than endogenous NF-L mRNAs, and a corresponding increase in NF-L subunits was found in axons arising from these neurons. Myelinated nerve fibers of transgenic animals contained increased numbers of NFs, assembled predominantly of NF-L. This was reflected in an increase in the density of axonal NFs; axonal caliber was not affected.

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Section: Discussionmentioning

confidence: 93%

Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber.

Monteiro

Hoffman

Gearhart

et al. 1990

The Journal of Cell Biology

160

View full text Add to dashboard Cite

show abstract

“…Considerable evidence now suggests that these tracks are microtubules (Shah et al, 2000;Wagner et al, 2004;Francis et al, 2005;He et al, 2005). Thus, it is interesting to note that morphometric studies on axonal cytoskeletons in vivo have demonstrated that neurofilaments generally outnumber microtubules, at least in large myelinated axons, with estimates of the neurofilament/ microtubule ratio ranging from 7/1 to 97/1, depending on the neuronal cell type (Price et al, 1988;Reles and Friede, 1991). In these axons, it is clear that not all neurofilaments can be adjacent to a microtubule.…”

Section: Discussionmentioning

confidence: 99%

Neurofilaments Switch between Distinct Mobile and Stationary States during Their Transport along Axons

Trivedi

Jung²,

Brown³

2007

J. Neurosci.

139

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We have developed a novel pulse-escape fluorescence photoactivation technique to investigate the long-term pausing behavior of axonal neurofilaments. Cultured sympathetic neurons expressing a photoactivatable green fluorescent neurofilament fusion protein were illuminated with violet light in a short segment of axon to create a pulse of fluorescent neurofilaments. Neurofilaments departed from the photoactivated regions at rapid velocities, but the overall loss of fluorescence was slow because many of the neurofilaments paused for long periods of time before moving. The frequency of neurofilament departure was more rapid initially and slower at later times, resulting in biphasic decay kinetics. By computational simulation of the kinetics, we show that the neurofilaments switched between two distinct states: a mobile state characterized by intermittent movements and short pauses (average ϭ 30 s) and a stationary state characterized by remarkably long pauses (average ϭ 60 min). On average, the neurofilaments spent 92% of their time in the stationary state. Combining short and long pauses, they paused for 97% of the time, resulting in an average transport rate of 0.5 mm/d. We speculate that the relative proportion of the time that neurofilaments spend in the stationary state may be a principal determinant of their transport rate and distribution along axons, and a potential target of mechanisms that lead to abnormal neurofilament accumulations in disease.

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“…In each case, systematic sampling of nonoverlapping fields resulted in sampling 50 -80% of the total myelinated fibers in each nerve. Neurofilament density and number in the sural nerve were calculated as previously described (27). Thin sections (60 nm) were cut with a diamond knife and stained with uranyl acetate and bismuth subnitrate before being viewed with a Zeiss 10 electron microscope operated at 80 keV.…”

Section: Methodsmentioning

confidence: 99%

Neurotrophin-3 Prevents the Proximal Accumulation of Neurofilament Proteins in Sensory Neurons of Streptozocin-Induced Diabetic Rats

et al. 2003

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The relation between neurofilament expression and/or phosphorylation in the proximal versus distal components of the sensory peripheral neuraxis was studied and related to disorders in structure and function of the distal axon of streptozocin (STZ)-induced diabetic rats studied for 14 weeks. The ability of neurotrophin-3 (NT-3) to prevent abnormalities in neurofilament biology was also investigated. Compared with age-matched controls, neurofilament heavy (NF-H) (3.3-fold) and neurofilament medium (NF-M) (2.5-fold), but not neurofilament light (NF-L), subunits accumulated in the proximal axon of sensory neurons of the lumbar dorsal root ganglia (DRG) in untreated diabetic rats. Neurofilament accumulation was prevented by NT-3. Smalland large-diameter sensory neurons exhibited elevated levels of NF-H protein accumulation and phosphorylation in the DRG of untreated diabetic rats, levels that were ameliorated by NT-3. The sural nerve of untreated diabetic rats showed a 50% decrease in the levels of NF-H and NF-M, but not NF-L, subunits; NT-3 only partially normalized the defect in NF-M expression. These observations were associated with significant lowering of motor and sensory nerve conduction velocity but no alteration in the mean axonal diameter of myelinated axons in the sural nerve in untreated diabetic rats. It is proposed that the accumulation of NF-H and NF-M subunits in the proximal axon is an etiologic factor in the distal axon degeneration observed in diabetes. [NF-L]). In the streptozocin (STZ) and BB rodent models of type 1 diabetes, structural abnormalities in peripheral nerve include decreased axonal caliber or axonal dwindling (1-3). Studies in type 1 diabetic rats show reduced expression of neurofilaments in sensory neurons (1,4,5), reduced axonal transport of neurofilament in sensory axons (6), loss of neurofilament in distal nerve (1-3,7), and abnormal neurofilament phosphorylation in the dorsal root ganglia (DRG), spinal cord, and sciatic nerve (8 -11). Aberrant phosphorylation of NF-H and NF-M subunits in DRG of STZ-and BB-diabetic rats is associated with activation of c-jun NH 2 -terminal kinase (JNK) (10). The stress-activated protein kinases (SAPKs: extracellular signal-regulated kinase [ERK], JNK, and p38) are well-characterized proteins that phosphorylate neurofilaments and are activated by hyperglycemia and oxidative stress in cultured sensory neurons (11-13).Nerve crushϪinduced loss of neurofilament expression in the small-to-medium subpopulation of neurons in the DRG is ameliorated by nerve growth factor treatment (14,15). Sequestration of the high-affinity receptor for neurotrophin-3 (NT-3) results in motor and sensory nerve conduction velocity (NCV) deficits similar to those that develop after nerve transection (16). Exogenous NT-3 provided after physical nerve injury can prevent and reverse a range of injury-evoked responses (16 -18) and also enhance subsequent regeneration (19). Systemic NT-3 treatment has also been shown to prevent toxin-induced peripheral neuropathies (20,21). Dem...

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Neurofilaments are spaced randomly in the radial dimension of axons

Cited by 76 publications

References 17 publications

Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber.

Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber.

Neurofilaments Switch between Distinct Mobile and Stationary States during Their Transport along Axons

Neurotrophin-3 Prevents the Proximal Accumulation of Neurofilament Proteins in Sensory Neurons of Streptozocin-Induced Diabetic Rats

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