Neurofilaments and glial filaments

The structure of neurofilaments and glial filaments are compared. Both filaments are composed of three subunits-a globule, interconnecting crossbar and side-arms. These elements form a tubular arrangement and their dimensions are given. Since the subunits of both filaments have a similar arrangement but differ in size, it is concluded that they represent different proteins.     

Neurofilaments and motor neuron disease

Amyotrophic lateral sclerosis (ALS) is an adult-onset and heterogeneous neurological disorder that affects primarily motor neurons in the brain and spinal cord. Although multiple genetic and environmental factors might be implicated in ALS, the striking similarities in the clinical and pathological features of sporadic ALS and familial ALS suggest that similar mechanisms of disease may occur. A common and perhaps universal pathological finding in ALS is the presence of abnormal accumulations of neurofilaments (often called spheroids or Lewy body-like deposits) in the cell body and proximal axon of surviving motor neurons. Such neurofilament deposits have been widely viewed as a consequence of neuronal dysfunction, perhaps reflecting axonal transport defects. This review discusses the emerging evidence, based primarily on transgenic mouse studies and on the discovery of deletion mutations in a neurofilament gene associated with ALS, that neurofilament proteins can play a causative role in motor neuron disease.     

Chromatin Proteins Share Antigenic Determinants with Neurofilaments

Antigenic determinants common to distinct proteins may be unambiguously identified by the use of monoclonal antibodies. Some monoclonal antibodies to mammalian neurofilaments have recently been shown to cross-react with the neurofibrillary tangles found at high density in the brains of senile dements with Alzheimers disease (SDAT). Here, we show that these antibodies also cross-react with chromatin proteins, including the linker histones H1 and H1(0). Elevated levels of histone H1(0) have also been reported in SDAT brains.     

Neurofilaments: abundant but mysterious neuronal structures

Neurofilaments are by far the most obvious elements of the neuronal cytoskeleton. Their subunits are biochemically among the most abundant neuron specific components, particularly in axons. Clearly they must be important to the neuron or they would not be so numerous But what do they do?.     

Distinctly Phosphorylated Neurofilaments in Different Classes of Neurons

Abstract: Recent immunohistochemical experiments revealed that specific anti-neurofilament monoclonal antibodies yield distinct patterns in different types of neurons. This led to the suggestion that neurofilaments are a family of heterogeneous molecules whose occurrence and distribution are a function of cell type. In the present study we examined the hypothesis that this heterogeneity is due to differences in the extent of phosphorylation of neurofilament proteins in distinct types of neurons. In view of the large number of potential phosphorylation sites on the heavy neurofilament protein (NF-H), we focused on this protein and examined its extent of phosphorylation in different types of neurons. This was performed using neurofilaments isolated from axons of the cholinergic bovine ventral root motor neurons and of the chemically heterogeneous bovine dorsal root neurons. Two-dimensional gel electrophoresis revealed that the isoelectric point of ventral root NF-H (pl 5.10) was ∼0.2 pl units more acidic than that of dorsal root NH-F. This difference was abolished by treating the neurofilaments with alkaline phosphatase, suggesting that the excess negative charge of ventral root NF-H is due to increased levels of phosphorylation. Amino acid analysis confirmed that the phosphoserine content of ventral root NF-H (27.2 ± 2.5% of the serines) is markedly higher than that of dorsal root NF-H (15.5 ± 6.2% of the serines). These findings provide a novel system for studying the biochemistry and function of distinctly phosphorylated neurofilaments in different types of neurons.     

A 350-S recovery period does not necessarily allow complete recovery of peak power output during repeated cycling sprints

The aim of this study was to determine whether a 350-s recovery period allows recovery of peak power output (PPO) to its initial value under the condition of a blood lactate (La) concentration higher than 10 mmol.L-1 during repeated cycling sprints (RCS). RCS (10x10-s cycling sprints) were performed under two conditions. Under one condition, the recovery period of RCS was fixed at 35 s (RCS35), and under the other condition, a 350-s recovery period was set before the 5th and 9th sets, and a 35-s recovery period was set before the other sets (RCScomb). In RCScomb, PPO in the 5th set recovered to that in the 1st set, but PPO in the 9th set did not. Under both conditions, blood La concentration progressively increased and reached approximately 14 mmol.L-1 at the end of the RCS. In RCScomb, VO2 immediately before the 5th set was not significantly different from that immediately before the 9th set. Mean power frequency (MPF) values estimated by a surface electromyogram from the vastus lateralis in the 5th and 9th sets were significantly higher in RCScomb than in RCS35. In conclusion, a 350-s recovery period does not allow recovery of PPO to its initial value under the condition of a blood La concentration of 14 mmol.L-1 during RCS.     

Neurofilaments and microtubules in sensory neurons after peripheral nerve section

Summary Sensory neurons were examined in spinal ganglia of the rat 1 to 55 days after section of the plexus brachialis nerves. Only light neurons of the type A were investigated. Maximal reaction to axotomy was found 7 to 14 days after the operation. The majority of the axotomized perikarya developed central chromatolysis. In such neurons, Nissl bodies virtually disappeared from the central area of the neuron and formed a more or less continuous zone at the cell circumference. The cytocentrum became filled with large numbers of mitochondria, dense bodies and other organelles. Neurofilaments and microtubules were disarranged and ran at random among the accumulated particles. Microtubules were often more prominent in chromatolytic areas than neurofilaments. Both these organelles were rare in the peripheral areas filled with massed Nissl substance.Part of the neurons that did not show typical chromatolysis contained increased numbers of neurofilaments among Nissl bodies dispersed throughout the cytoplasm. Neurofilaments were roughly arrayed in bundles up to several microns wide; they were linked by cross-bridges and separated by distances of about 500 Å. Microtubules were rarely found in the filamentous areas. However, they were numerous in the axon hillock and in the initial segment where they formed fascicles similar to those described in normal neurons of other types.During the period from 14 to 55 days after axotomy, many perikarya recovering from chromatolysis contained enlarged bundles of neurofilaments with occasional microtubules among the restored Nissl bodies.Mean diameters of sensory neurons, measured 7 to 55 days after axotomy, in no instance exceeded those of contralateral control neurons. It thus appears that sensory perikarya do not increase in size either during the chromatolytic process or during the period of recovery.This project was supported by a grant from the Muscular Dystrophy Association of America, Inc. The main part of this study was done while the author was a Research Fellow in Anatomy at the Harvard Medical School, Boston. The author wishes to thank prof. S. L. Palay for his valuable advice and help received during her stay at the Department of Anatomy at the Harvard Medical School, under NIH training grant NBO5591.     

Tubulin acetylation alone does not affect Kinesin-1 velocity and run length in vitro

Kinesin-1 plays a major role in anterograde transport of intracellular cargo along microtubules. Currently, there is an ongoing debate of whether α-tubulin K40 acetylation directly enhances the velocity of kinesin-1 and its affinity to the microtubule track. We compared motor motility on microtubules reconstituted from acetylated and deacetylated tubulin. For both, single- and multi-motor in vitro motility assays, we demonstrate that tubulin acetylation alone does not affect kinesin-1 velocity and run length.     

Creatine supplementation and performance in 6 consecutive 60 meter sprints

Creatine is an ergogenic aid used in individual and team sports. The aim of this study is to analyze the effect of monohydrate creatine supplementation on physical performance during 6 consecutive maximal speed 60 meter races, and the changes induced in some characteristic biochemical and ventilatory parameters. The study was carried out on nineteen healthy and physically active male volunteers, and randomly distributed into two groups: Group C received a supplement of creatine monohydrate (20 g/day for 5 days) and group P received placebo. Tests were performed before and after supplementation. No significant changes were observed in weight or body water measured by bioimpedance or the sum of 7 skinfold or performance during the 60 meter races. Group C showed a statistically significant increase in plasma creatinine from 69.8 +/- 12.4 to 89.3 +/- 12.4 micromol x L(-1) (p<0.05). In group C in the second control day (after creatine supplementation), expiratory volume V(E), O2 uptake and CO2 production were lower after 2 minutes of active recovery period. These results indicate that creatine monohydrate supplementation does not appear to improve the performance in 6 consecutive 60 meter repeated races but may modify ventilatory dynamics during the recovery after maximal effort.     

Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links

Abstract

Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently binds amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated to be intimately associated with pathological lesions of Alzheimer's disease (AD), suggesting that oxidative stress is a major component in the disease. Here, we examined the HNE-cross-linking modifications by using an antibody specific for a lysine–lysine cross-link. Since in a prior study we noted no immunolabeling of neuritic plaques or neurofibrillary tangles but instead found strong labeling of axons, we focused this study on axons. Axonal labeling was examined in mouse sciatic nerve, and immunoblotting showed the cross-link was restricted to neurofilament heavy and medium subunits, which while altering migration, did not indicate larger NF aggregates, indicative of intermolecular cross-links. Examination of mice at various ages showed the extent of modification remaining relatively constant through the life span. These findings demonstrate lipid-cross-linking peroxidation primarily involves lysine-rich neurofilaments and is restricted to intramolecular cross-links.     

Neurofilaments and microtubules in anterior horn cells of the rat

Dendrites arising from the larger nerve cells in the anterior horn contain fascicles of neurofilaments in addition to the usual dendritic components From a comparison of neurofilaments and microtubules, and their respective subunits it is concluded that direct mterconversion between them is improbable In transverse section the wall of the neurofilament is composed of 4-6 circular densities about 30 A in diameter Short spokelike side arms project from the circular densities into the surrounding cottony matrix in which the filaments are embedded.