Electrophysiological properties of axons in mice lacking neurofilament subunit genes: disparity between conduction velocity and axon diameter in absence of NF-H

Križ, Jasna; Zhu, Qinzang; Julien, Jean‐Pierre; Padjen, Ante L.

doi:10.1016/s0006-8993(00)02899-7

Cited by 108 publications

(90 citation statements)

References 74 publications

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“…We have shown a disparity between the unchanged axon calibre and decreased conduction velocity in peripheral nerves of transgenic mice with neurofilament H knock-out [35]. These findings point out that change in axonal membrane properties, such as reported in this study, are more likely to affect conduction velocity.…”

Section: Reduction Of CV In Experimental Diabetic Neuropathysupporting

confidence: 73%

“…Axons were considered suitable for experiments if the resting membrane potential after stabilization was more negative than −65 mV (in control animals). Unlike amphibian, the depolarizing afterpotentials (DAPs) are observed only in 15% of sampled axons in mammalian axons [32,33,34,35,36] and therefore they were not studied. The microelectrode technique used in this study allows recording from undissected axons; it is likely that that such recordings reflect the excitability in vivo well [20,30].…”

Section: Methodsmentioning

confidence: 99%

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Intra-axonal recording from large sensory myelinated axons: Demonstration of impaired membrane conductances in early experimental diabetes

Križ

Padjen

2003

Diabetologia

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Aim/hypothesis. Diabetic neuropathy is accompanied by a range of positive (paresthaesia, dysesthaesia, pain) and negative (hypesthaesia, anesthaesia) neurological symptoms suggesting widespread alterations in axonal excitability. The nature and the mechanisms underlying these alterations in axonal excitability are not well understood. The aim of this study was to examine the extent of changes in membrane properties of an identified neuronal structure -the large myelinated sensory axons in early experimental diabetes in rats. Methods. Intra-axonal microelectrode recordings from large sensory myelinated axons from the isolated sural nerve in short-term streptozotocin-induced diabetic rats were used to study membrane properties using standard current-clamp technique.Results. In addition to decreased conduction velocity we found several differences in physiological properties of sensory axons from diabetic rats: decreased resting membrane potential, decreased single action potential amplitude associated with slower rate of rise and decrease in inward rectification associated with slight alteration in outwardly rectifying conductances indicating impaired potassium conductances. Conclusion/Interpretation. These results extend previous indirect evidence that potassium and sodium ionic conductances, most notably the inward rectifier (IR, I h ), are altered in large sensory axons of diabetic rats. . The pathogenesis of diabetic neuropathies and consequently their treatment remain elusive, in spite of a number of hypotheses advanced in the past decades. These hypotheses deal with several major areas, such as metabolic, ischaemia and oxidative stress, non-specific glycosylation, and disturbances in trophic factors [1,2,3,4]. The histopathological findings of advanced diabetic neuropathy (DN) are characterized by axonal degeneration, demyelination and atrophy that are associated with highly diverse disturbances of peripheral nerve function [2,5,6]. Different positive and negative neurological signs associated with DN suggest modification in axonal membrane excitability. Indeed, one of the earliest detectable physical signs of early DN is a decrease in conduction velocity as signsThe peripheral neuropathy associated with diabetes is one of the most common polyneuropathies, and at least 50% of diabetic patients will develop a form of

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Section: Reduction Of CV In Experimental Diabetic Neuropathysupporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Intra-axonal recording from large sensory myelinated axons: Demonstration of impaired membrane conductances in early experimental diabetes

Križ

Padjen

2003

Diabetologia

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“…Furthermore, distribution of the mitochondria inside the axon is essential to control ATP levels and cell-to-cell communication. The NEFM polypeptide (52) protein and the Dynamin-related protein (Drp-1) (53) are the main proteins involved in these events. Furthermore, ER stress activates CREB through TOX3, and CREB is a target gene of miR-34a and is involved in neurite growth and synaptic plasticity (54,55).…”

Section: Identification Of Genes Regulated By Tat In Neurons-mentioning

confidence: 99%

HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs

Chang

Mukerjee

Bagashev

et al. 2011

Journal of Biological Chemistry

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Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release from the infected cells and taken up by noninfected cells. Using microRNA array assay, we demonstrated that Tat deregulates the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a target genes such as CREB protein as shown by real time PCR. The effect of Tat was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increase in Tat transgenic mice when compared with the parental mice. Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent.

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“…Conduction properties are influenced further by axon caliber (Sakaguchi et al, 1993;Kriz et al 2000), internodal length (Court et al, 2004), and the molecular structure of nodes of Ranvier (Bhat et al, 2001;Boyle et al, 2001). Early ultrastructural investigations demonstrated that myelinated fibers develop stereotyped ratios between axon caliber, myelin thickness, and internodal distances.…”

Section: Introductionmentioning

confidence: 99%

“…As demonstrated in multiple animal models with absent or disorganized NFs, they play an essential role in axon radial growth (Cleveland et al 1991;Sakaguchi et al, 1993;Elder et al, 1999;Jacomy et al, 1999). However, because mice null for heavy NF subunit (NFH) achieve normal axonal calibers but conduct action potentials at reduced speeds, NFs control more than the physical dimensions of axons (Kriz et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Axonal Neurofilaments Control Multiple Fiber Properties But Do Not Influence Structure or Spacing of Nodes of Ranvier

Perrot

Lonchampt²,

Peterson³

et al. 2007

J. Neurosci.

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In the vertebrate nervous system, axon calibers correlate positively with myelin sheath dimensions and electrophysiological parameters including action potential amplitude and conduction velocity. Neurofilaments, a prominent component of the neuronal cytoskeleton, are required by axons to support their normal radial growth. To distinguish between fiber features that arise in response to absolute axon caliber and those that are under autonomous control, we investigated transgenic mice in which neurofilaments are sequestered in neuronal cell bodies. The neurofilament deficient axons in such mice achieve mature calibers only 50% of normal and have altered conduction properties. We show here that this primary axonal defect also induces multiple changes in myelin sheath composition and radial dimensions. Remarkably, other fundamental fiber features, including internodal spacing and the architecture and composition of nodes of Ranvier, remain unaltered. Thus, many fiber characteristics are controlled through mechanisms operating independently of absolute axon caliber and the neurofilament cytoskeleton.

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Electrophysiological properties of axons in mice lacking neurofilament subunit genes: disparity between conduction velocity and axon diameter in absence of NF-H

Cited by 108 publications

References 74 publications

Intra-axonal recording from large sensory myelinated axons: Demonstration of impaired membrane conductances in early experimental diabetes

Intra-axonal recording from large sensory myelinated axons: Demonstration of impaired membrane conductances in early experimental diabetes

HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs

Axonal Neurofilaments Control Multiple Fiber Properties But Do Not Influence Structure or Spacing of Nodes of Ranvier

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