Axonal dysfunction is the major phenotypic change in many neurodegenerative diseases, but the processes underlying this impairment are not clear. Modifier of cell adhesion (MOCA) is a presenilin binding protein that functions as a guanine nucleotide exchange factor for Rac1. The loss of MOCA in mice leads to axonal degeneration and causes sensorimotor ...

Axonal dysfunction is the major phenotypic change in many neurodegenerative diseases, but the processes underlying this impairment are not clear. Modifier of cell adhesion (MOCA) is a presenilin binding protein that functions as a guanine nucleotide exchange factor for Rac1. The loss of MOCA in mice leads to axonal degeneration and causes sensorimotor ...

The local caliber of mature axons is largely determined by neurofilament (NF) content. The axoskeleton, mainly consisting of NFs, however, is dynamic. NFs are assembled in the cell body and are transported by molecular motors on microtubule tracks along the axon at a slow rate of fractions of mm per day. We combine live cell ...

Multipolar neurons in the mammalian nervous system normally exhibit one axon and several dendrites. However, in response to an axonal injury, adult motoneurons may regenerate supernumerary axons. Supernumerary axons emerge from the cell body or dendritic trees in addition to the stem motor ...

Demyelinating diseases, such as multiple sclerosis, are characterized by inflammatory demyelination and neurodegeneration of the central nervous system. Therapeutic strategies that induce effective neuroprotection and enhance intrinsic repair mechanisms are central goals for future therapy of multiple sclerosis. Oestrogens and oestrogen receptor ligands are promising treatments to prevent multiple ...

... Studies of Kinesins and Axonal Transport in a Mouse Model of NF1. ... in a quantitative defect in axonal transport in the peripheral nervous system. ...

In the hallmark neuritic dystrophy of Alzheimer's disease (AD), autophagic vacuoles containing incompletely digested proteins selectively accumulate in focal axonal swellings, reflecting defects in both axonal transport and autophagy. Here, we investigated the possibility that impaired lysosomal proteolysis could be a basis for both of ...

The pathophysiologic events in optic nerve axons have recently been recognized as crucial to an understanding of clinically significant acquired alterations in the ophthalmoscopic appearance of the optic disc. Stasis and related abnormalities of axonal transport appear to explain most aspects of optic nerve head ...

The tauopathies are a group of disorders characterised by aggregation of the microtubule-associated protein tau and include Alzheimer's disease (AD) and the fronto-temporal dementias (FTD). We have used Drosophila to analyse how tau abnormalities cause neurodegeneration. By selectively co-expressing wild-type human tau (0N3R isoform) and a GFP vesicle marker in motorneurons, ...

Growing evidence suggests that amyloid beta (A?) and tau pathologies are strongly associated with mitochondrial dysfunction and neuronal damage in Alzheimer's disease (AD). Extensive research of AD postmortem brains, mouse and fly models, including triple transgenic AD mice and mutant tau mice, and cell culture studies revealed that tau hyperphosphorylation is caused by multiple factors, including ...

... Accession Number : ADP004021. Title : Pathology and Axonal Transport in Hexacarbon Neuropathies,. Corporate Author ...

Mutations of the spastin gene (Sp) are responsible for the most frequent autosomal dominant form of spastic paraplegia, a disease characterized by the degeneration of corticospinal tracts. We show that a deletion in the mouse Sp gene, generating a premature stop codon, is responsible for progressive axonal degeneration, restricted to the central nervous system, leading to a ...

The retrograde axonal transport of intravenously (i.v.) administered /sup 125/I-nerve growth factor (/sup 125/I-NGF) was examined in mesenteric nerves innervating the small bowel of rats with streptozocin (STZ) diabetes using methods described in detail in the companion article. The accumulation of /sup 125/I-NGF distal to a ligature on the ileal ...

The mechanism of nerve cell transport, the process by which substances made in a nerve cell body are moved long distances along a nerve cell process or axon, remains a major unsolved problem in biomedicine. Using a light microscope with the recently developed video enhanced contrast method with interference contrast optics, it is possible to detect small ...

BackgroundMembers of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.Methodology/Principal ...

Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is a late-onset motor neuron disease (MND) caused by an abnormal expansion of the CAG repeat in the androgen receptor (AR) gene on the X-chromosome, encoding a polyglutamine (poly-Q) sequence in the protein product. Mutant poly-Q-expanded AR protein is widely expressed but leads to selective lower motoneuron ...

Infantile neuroaxonal dystrophy (INAD) is a fatal neurodegenerative disease characterized by the widespread presence of axonal swellings (spheroids) in the CNS and PNS and is caused by gene abnormality in PLA2G6 [calcium-independent phospholipase A(2)? (iPLA(2)?)], which is essential for remodeling of membrane phospholipids. To clarify the pathomechanism ...

... Accession Number : ADA487439. Title : Studies on Axonal Transport in an Animal Model for Gulf War Syndrome. Descriptive Note : Final rept. ...

of neurofilaments, probably those that are being actively transported in the axon. Furthermore, some filaments58 The bulk of neuronally synthesized proteins destined for the axon is transported in a phase of transport ~100 times slower (1 mm/day) than the vesicular traffic of fast ...

The carboxy-terminal side arm of the neurofilament high subunit consists of a highly phosphorylated domain and a negatively charged region. Multiple evidences suggested that these domains are essential for the axonal phosphorylation and transport of neurofilaments and play a role in their abnormal accumulation following chemical ...

Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. ...

After repeated exposure, acrylamide (AC) produces degeneration of distal axons. Because neurons whose axons have been injured (e.g. by axotomy) show alterations in their structural and chemical properties, the present study was designed to differentiate the direct effects of AC intoxication from neuronal responses secondary to axonal ...

Regenerating sensory axons in the dorsal roots of adult mammals are stopped at the junction between the root and spinal cord by reactive astrocytes. Do these cells stop axonal elongation by activating the physiological mechanisms that normally operate to stop axons during development, or do they physically obstruct the elongating ...

Cytoplasmic protein transport in axons ('slow axonal transport') is essential for neuronal homeostasis, and involves Kinesin-1, the same motor for membranous organelle transport ('fast axonal transport'). However, both molecular mechanisms of slow ...

Cytoplasmic protein transport in axons (�slow axonal transport') is essential for neuronal homeostasis, and involves Kinesin-1, the same motor for membranous organelle transport (�fast axonal transport'). However, both molecular mechanisms of slow ...

The microtubule-associated protein Tau is found in large amount in axons of neurons and is involved in human neurodegenerative diseases called tauopathies, which include Alzheimer's disease. In these diseases, the Tau protein is abnormally hyperphosphorylated and one therapeutic strategy currently under consideration consists in inhibiting Tau ...

Type I lissencephaly or agyria-pachygyria is a rare developmental disorder which results from a defect of neuronal migration. It is characterized by the absence of gyri and a thickening of the cerebral cortex and can be associated with other brain and visceral anomalies. Since the discovery of the first genetic cause (deletion of chromosome 17p13.3), six additional genes have been found to be ...

Radioautography permits to distinguish various pathways within the axons: the axoplasm which includes soluble enzymes and constituents of the cytoskeleton moving with slow axoplasmic flow; the mitochondria which are conveyed as organelles; the smooth endo...

The velocity of axonal transport of protein labeled with (/sup 3/H)leucine was determined in rat sciatic nerve sensory axons after reversible cooling of the nerve, which provoked a local accumulation of transported material. The velocity of the wavefront of the labeled protein, as well as the slope of the ...

Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on ...

The direct modulation of subthalamic nucleus (STN) neurons by dopamine (DA) neurons of the substantia nigra (SN) is controversial owing to the thick caliber and low density of DA axons in the STN. The abnormal activity of the STN in Parkinson's disease (PD), which is central to the appearance of symptoms, is therefore thought to result from the loss of DA ...

UNC-6/Netrin is an evolutionarily conserved, secretory axon guidance molecule. In Caenorhabditis elegans, UNC-6 provides positional information to the axons of developing neurons, probably by establishing a concentration gradient from the ventral to the dorsal side of the animal. Although the proper localization of UNC-6 is important for accurate neuronal ...

The optic nerve of the rat has been examined by light and electron microscopy, and also for vascular permeability to fluorescently labelled albumin, 2 days to 34 weeks after crushing in the orbit. The operation was usually followed by loss of 20-70% of the retinal ganglion cells. Axons could be followed from the retina into the optic nerve at all postoperative times, but they ...

The alpha-7 subunit of the nicotinic acetylcholine receptor (?7nAChR) is expressed in the prefrontal cortex (PFC), a brain region where these receptors are implicated in cognitive function and in the pathophysiology of schizophrenia. Activation of this receptor is dependent on release of acetylcholine (ACh) from axon terminals that contain the vesicular acetylcholine ...

Charcot-Marie-Tooth disease is characterized by length-dependent axonal degeneration with distal sensory loss and weakness, deep-tendon-reflex abnormalities, and skeletal deformities. It is caused by mutations in more than 40 genes. We investigated a four-generation family with 23 members affected by the axonal form (type 2), for which ...

Amyloid-? (A?) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer�s disease (AD). How exactly they impair cognitive functions is unknown. Here we assessed the effects of A? and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are ...

Neurons transmit long-range biochemical signals between cell bodies and distant axonal sites or termini. To test the hypothesis that signaling molecules are hitchhikers on axonal vesicles, we focused on the c-Jun NH₂-terminal kinase (JNK) scaffolding protein Sunday Driver (syd), which has been proposed to link the molecular motor ...

Spontaneous regrowth of retinal ganglion cell (RGC) axons occurs after optic nerve (ON) transection in the lizard Gallotia galloti. To gain more insight into this event we performed an immunohistochemical study on selected neuron and glial markers, which proved useful for analyzing the axonal regrowth process in different regeneration models. In the ...

The simple pathoanatomic concept that a narrowed spinal canal causes compression of the enclosed cord, leading to local tissue ischemia, injury, and neurological impairment, fails to explain the entire spectrum of clinical findings observed in cervical spondylotic myelopathy. A growing body of evidence indicates that spondylotic narrowing of the spinal canal and abnormal or ...

The glycine transporter subtype 2 (GlyT2) is localized in the axon terminals of glycinergic neurons. Mice deficient in GlyT2 are normal at birth but during the second postnatal week develop a lethal neuromotor deficiency that resembles severe forms of human hyperekplexia (hereditary startle disease) and is characterized by spasticity, tremor, and an ...

Presenilins (PS) play a central role in ?-secretase-mediated processing of ?-amyloid precursor protein (APP) and numerous type I transmembrane proteins. Expression of mutant PS1 variants causes familial forms of Alzheimer's disease (FAD). In cultured mammalian cells that express FAD-linked PS1 variants, the intracellular trafficking of several type 1 membrane proteins is altered. We now report ...

Whether the axonal framework is stationary or moves is a central debate in cell biology. To better understand this problem, we developed a mathematical model that incorporates force generation at the growth cone, the viscoelastic properties of the axon, and adhesions between the axon and substrate. Using force-calibrated needles to ...

The mechanical integrity of the axon in mature axons is provided by neurofilaments(NF). NFs move through the axon at the average slow rate of 0.5mm/day, characterized by bursts of movement and extended pauses in between. The local number of NFs determines the local axonal caliber and as a result, the kinetics of NF ...

Axons are occupied by dense arrays of cytoskeletal elements called microtubules, which are critical for generating and maintaining the architecture of the axon, and for acting as railways for the transport of organelles in both directions within the axon. Microtubules are organized and regulated by molecules that ...

The intent of the study was to determine the effect of intermittent, acute, and subchronic p(bar)-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested r...

The effects of acrylamide on fast axonal transport have been measured primarily using the indirect methods of isotope or enzyme accumulation. The authors report the first direct evaluation of the effects of subchronic acrylamide dosing (150, 300, or 500 m...

the retina to the thalamus are abnormal and growth cones of retinal axons from these mice fail to collapseTouch and go: guidance cues signal to the growth cone cytoskeleton Katherine Kalil1 and Erik W Dent2 Growth cones, the highly motile tips of growing axons, guide axons to their targets by responding

The morphology of alphaherpesviruses during anterograde axonal transport from the neuron cell body towards the axon terminus is controversial. Reports suggest that transport of herpes simplex virus type 1 (HSV-1) nucleocapsids and envelope proteins occurs in separate compartments and that complete virions form at ...

, or months that they spend traveling down the axon. Whether the movement is considered to be fast or slowSlow Axonal Transport A Brown, Ohio State University, Columbus, OH, USA � 2009 Elsevier Ltd. All patterns of movement, termed fast and slow. Fast axo- nal transport represents the movement of membranous

Purpose. Diffusion tensor imaging (DTI) measures the random motion of water molecules reflecting central nervous system tissue integrity and pathology. Glaucoma damages retinal ganglion cells (RGCs) and their axons. The authors hypothesized that DTI-derived axonal and myelin injury biomarkers may be used to detect early axonal damage ...

Neurotropic herpesviruses depend on long-distance axon transport for the initial establishment of latency in peripheral ganglia (retrograde transport) and for viral spread in axons to exposed body surfaces following reactivation (anterograde transport). Images of neurons infected with herpes ...

Neurotropic herpesviruses depend on long-distance axon transport for the initial establishment of latency in peripheral ganglia (retrograde transport) and for viral spread in axons to exposed body surfaces following reactivation (anterograde transport). Images of neurons infected with herpes ...

According to the �stop-and-go� hypothesis of slow axonal transport, cytoskeletal and cytosolic proteins are transported along axons at fast rates but the average velocity is slow because the movements are infrequent and bidirectional. To test whether this hypothesis can explain the kinetics of slow ...

This paper develops a model of nanoparticle transport in neurons. It is assumed that nanoparticles are transported inside endocytic vesicles by a combined effect of dynein-driven transport and diffusion. It is further assumed that in axons nanoparticles are internalised only at axon terminals, ...

ALS is a fatal neurodegenerative disease characterized by selective motor neuron death resulting in muscle paralysis. Mutations in superoxide dismutase 1 (SOD1) are responsible for a subset of familial cases of ALS. Although evidence from transgenic mice expressing human mutant SOD1^G93A suggests that axonal transport defects may ...

Locally generating new proteins in subcellular regions provides means to spatially and temporally modify protein content in polarized cells. Recent years have seen resurgence of the concept that axonal processes of neurons can locally synthesize proteins. Experiments from a number of groups have now shown that axonal protein synthesis helps to initiate ...

Rapid axonal transport in rabbit vagus nerve was studied during and after graded nerve compression. Proteins of the rapid axonal transport were labelled by micro-injection of 3H-leucine into the nodose ganglion and the cervical vagus nerve was subjected to graded compression by a small "mini-cuff" applied directly ...

This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann ...

Presynaptic, electron-dense, cytoplasmic protrusions such as the T-bar (Drosophila) or ribbon (vertebrates) are believed to facilitate vesicle movement to the active zone (AZ) of synapses throughout the nervous system. The molecular composition of these structures including the T-bar and ribbon are largely unknown, as are the mechanisms that specify their synapse-specific assembly and ...

Little is known about which components of the axonal cytoskeleton might break during rapid mechanical deformation, such as occurs in traumatic brain injury. Here, we micropatterned neuronal cell cultures on silicone membranes to induce dynamic stretch exclusively of axon fascicles. After stretch, undulating distortions formed along the ...

Flupirtine is an activator of Kv7 (KCNQ/M) potassium channels that has found clinical use as an analgesic with muscle relaxant properties. Kv7 potassium channels are expressed in axonal membranes and pharmacological activation of these channels may restore abnormal nerve excitability. We have examined the effect of flupirtine on the electrical excitability ...

Although autoradiography has demonstrated local incorporation of (3H)inositol into axonal phospholipids after intraneural injection (Gould, 1976; Gould et at., 1987b), retrograde axonal transport of phosphatidylinositol has only been demonstrated after in...

Although autoradiography has demonstrated local incorporation of [3H]inositol into axonal phospholipids after intraneural injection (Gould, 1976; Gould et at., 1987b), retrograde axonal transport of phosphatidylinositol has only been demonstrated after injection of lipid precurso...

Mini-Review Kinesin-II, a Membrane Traffic Motor in Axons, Axonemes, and Spindles Jonathan M and kinesin-II to serve as ax- onal vesicle transport motors that can be deployed as membrane traffic motors in other subcellular locations such as axonemes and spindles. Kinesin, a Vesicular Transport Motor in Axons

The effects of acrylamide on fast axonal transport have been measured primarily using the indirect methods of isotope or enzyme accumulation. e report the first direct evaluation of the effects of sub-chronic acrylamide dosing (150, 300 or 500 mg/kg total dose) on the fast axonal...

of proteins (Horton and Ehlers, 2003) (Fig- ure 1). Vesicular transport of membrane proteins to axons, Song et al. (2009) now find that in A Gate Keeper for Axonal Transport Shaohua Xiao1 and Lily Yeh Jan1, CA 94143, USA *Correspondence: lily.jan@ucsf.edu DOI 10.1016/j.cell.2009.03.003 The axon

Electron micrographic studies of neuronal axons have produced contradictory conclusions on how alphaherpesviruses are transported from neuron cell bodies to axon termini. Some reports have described unenveloped capsids transported on axonal microtubules with separate ...

It has been postulated that phosphorylation of the carboxy terminus sidearms of neurofilaments (NFs) increases axon diameter through repulsive electrostatic forces that increase sidearm extension and interfilament spacing. To evaluate this hypothesis, the relationships among NF phosphorylation, NF spacing, and axon diameter were examined in uninjured and ...

... A genetic abnormality results in abnormal transport of amino acids in the kidney. The high levels of the amino acid cystine in the urine lead to stone ...

These studies lead us to propose the following hypothesis. The earliest change in the axon following hexacarbon exposure is an alteration in the cytoskeleton, resulting in clusters of microtubule channels segregated from neurofilaments. Initially, fast an...

Biochemical and physiological studies in the giant axons of the Chilean squid Dosidicus Gigas were carried out in order to correlate metabolic dependent sodium transport and the enzymic profile of nerve membranes. Membrane fractions were isolated from the...

Neurofilament proteins are known to be transported along axons by slow axonal transport, but the form in which they move is controversial. In previous studies on cultured rat sympathetic neurons, we found that green fluorescent protein-tagged neurofilament proteins move predominantly in the form of filamentous ...

Within an axon bundle, one or two are pioneering axons and the rest are follower axons. Pioneering axons are projected first and the follower axons are projected later but follow a pioneering axon(s) pathway. It is not clear whether the pioneering axons ...

Increasing evidence suggests that the accumulation of amyloid beta (A?) in synapses and synaptic mitochondria causes synaptic mitochondrial failure and synaptic degeneration in Alzheimer's disease (AD). The purpose of this study was to better understand the effects of A? in mitochondrial activity and synaptic alterations in neurons from a mouse model of AD. Using primary neurons from a ...

Although it is well known that damage to neurons results in release of substances that inhibit axonal growth, release of chemical signals from damaged axons that attract axon growth cones has not been observed. In this study, a 532 nm 12 ns laser was focused to a diffraction-limited spot to produce site-specific damage to single ...

Investigation of axonal biology in the central nervous system (CNS) is hindered by a lack of an appropriate in vitro method to probe axons independently from cell bodies. Here we describe a microfluidic culture platform that polarizes the growth of CNS axons into a fluidically isolated environment without the use of targeting ...

N-cadherin is a classical type I cadherin that contributes to the formation of neural circuits by regulating growth cone migration and the formation of synaptic contacts. This study analyzed the role of N-cadherin in primary motor axons growth during development of the zebrafish (Danio rerio) embryo. After exiting the spinal cord, primary motor axons ...

Purpose: Heparan sulfate (HS) is abundantly expressed in the developing neural retina; however, their role in the intraretinal axon guidance of retinal ganglion cells (RGCs) remains unclear. In this study, we examined whether HS was essential for the axon guidance of RGCs towards the optic nerve head. Methods: We conditionally ablated the gene encoding the ...

Huntingtin-associated protein-1 (HAP1) was initially identified as an interacting partner of huntingtin, the Huntington disease protein. Unlike huntingtin that is ubiquitously expressed throughout the brain and body, HAP1 is enriched in neurons, suggesting that its dysfunction could contribute to Huntington disease neuropathology. Growing evidence has demonstrated that HAP1 and huntingtin are ...

Neurons are highly polarized cells, typically with a long axon and relatively short dendrites. A wealth of recent data has identified a number of signaling molecules that are involved in neuronal polarization. Kinesin superfamily proteins (KIFs) contribute to the establishment and maintenance of neuronal polarity by selectively transporting various ...

Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), suggesting abnormally increased excitability of motor axons. Previous nerve excitability studies have shown reduced axonal potassium currents in ALS patients that may contribute to the hyperexcitability and thereby generation of fasciculations. To ...

Organophosphate (OP)-based pesticides have been used extensively for decades and as a result they have become almost ubiquitous in our environment. There is clinical and animal evidence to suggest that chronic exposures to OPs can lead to cognitive dysfunction and other neurological abnormalities, although the mechanism for these effects is unknown. We previously reported that ...

The elaboration of neuronal axons and dendrites is dependent on a functional cytoskeleton. Cytoskeletal components have been shown to play a major role in the maintenance of the nervous system through adulthood, and changes in neurofilaments and microtubule-associated proteins (MAPs) have been linked to a variety of neurodegenerative diseases. Here we show that Futsch, the fly ...

Mitochondria are essential organelles for neuronal survival and play important roles in ATP generation, calcium buffering, and apoptotic signaling. Due to their extreme polarity, neurons utilize specialized mechanisms to regulate mitochondrial transport and retention along axons and near synaptic terminals where energy supply and calcium homeostasis are in ...

Proper transport and distribution of mitochondria in axons and at synapses are critical for the normal physiology of neurons. Mitochondria in axons display distinct motility patterns and undergo saltatory and bidirectional movement, where mitochondria frequently stop, start moving again, and change direction. While approximately ...

Dysimmune neuropathies, in common with other neuropathies, comprise an axonal impairment that it is primary or secondary to a demyelinating process. We consider here axonal impairment in the course of certain dysimmune neuropathies, such as the Guillain Barr� syndrome, chronic inflammatory demyelinating polyradiculoneuritis and multiple conduction block ...

Alphaherpesvirus infection of the mammalian nervous system is dependent upon the long-distance intracellular transport of viral particles in axons. How viral particles are effectively trafficked in axons to either sensory ganglia following initial infection or back out to peripheral sites of innervation following reactivation remains ...

The biological and clinical relevance of axonal transport has driven the development of a variety of new approaches to its study, including the generation of fluorescence or brightfield movies of moving cargoes within axons. Kymograph analysis is a simple and effective tool used to analyze axonal ...

The purpose of this study was to examine the hypothesis if repetition of mild mechanical brain injury induces the pathological process related to Alzheimer's disease. After defining the magnitude of the subthreshold brain injury which does not induce brain tissue damage by a single hit, the subthreshold mild impact (1.0 atm) was repeated 7 times every 24 h. One week after the last impact, ...

Axonal degeneration is a hallmark of many debilitating neurological disorders and is thought to be regulated by mechanisms distinct from those governing cell body death. Recently, caspase 6 activation via APP cleavage and activation of DR6 was discovered to induce axon degeneration after NGF withdrawal. We tested whether this pathway is involved in ...

Impaired axonal transport may play a key role in Parkinson's disease. To test this notion, a microchamber system was adapted to segregate axons from cell bodies using green fluorescent protein-labeled mouse dopamine (DA) neurons. Transport was examined in axons challenged with the DA ...

A systems approach was developed and implemented to simulate and analyze motor-assisted axonal transport in nervous system. The methodology employs a Galerkin based linear finite element solver of a system of three coupled partial differential equations governing axonal diffusion-reaction-advection with an efficient optimization ...

Axon-dendrite polarization is crucial for neural network wiring and information processing in the brain. Polarization begins with the transformation of a single neurite into an axon and its subsequent rapid extension, which requires coordination of cellular energy status to allow for transport of building materials to support ...

Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of NgCAM kinetically, ...

Microtubules are essential cytoskeletal tracks for cargo transportation in axons and also serve as the primary structural scaffold of neurons. Structural assembly, stability, and dynamics of axonal microtubules are of great interest for understanding neuronal functions and pathologies. However, microtubules are so densely packed in ...

SummaryMicrotubules are essential cytoskeletal tracks for cargo transportation in axons and also serve as the primary structural scaffold of neurons. Structural assembly, stability, and dynamics of axonal microtubules are of great interest for understanding neuronal functions and pathologies. However, microtubules are so densely packed ...

Caliber is an important feature of axons which is exquisitely tuned to its electrophysiologic function. Although there is a large variety of axonal calibers (even within one cell), the regulatory mechanisms giving rise to these shapes are not understood. Mechanical integrity of the mature neuronal axon is provided by neurofilaments ...

Real-time analyses have revealed that some newly synthesized neurofilament (NF) subunits translocate into and along axonal neurites by moving along the inner plasma membrane surface, suggesting that they may translocate against the submembrane actin cortex. We therefore examined whether or not NF axonal transport was dependent on actin ...

Distinct molecules are segregated into somatodendritic and axonal compartments of polarized neurons, but mechanisms underlying the development and maintenance of such segregation remain largely unclear. In cultured hippocampal neurons, we observed an ankyrin G- and F-actin-dependent structure that emerged in the cytoplasm of the axon initial segment (AIS) ...

induced or repressed by nerve regeneration, including galanin, neuropeptide Y, neurofilament, glial cell is transported throughout the regenerating axonal process (Fig. 2B). That the stained cells are regenerating DRG of neurons to regenerate an axon after injury is determined by both the surrounding environment and factors

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it is not known whether this neuronal damage is a primary disease process, or occurs only secondary to demyelination. In the current ...

Androgen receptors are expressed in many different neuronal populations in the central nervous system where they often act as transcription factors in the cell nucleus. However, recent studies have detected androgen receptor immunoreactivity in neuronal and glial processes of the adult rat neocortex, hippocampal formation, and amygdala as well as in the telencephalon of Eastern Fence and green ...

out from the cell body (Figs. 2A and B). At this stage, the HSN growth cone was observed at the tip cells. (A�C) Z-stack images of the ventral growth of the HSN neurons. (A) The ventral growth of the HSNR growth were also scored as abnormal. Dorsal growth: Axons that, after growing ventrally, failed to grow

Abnormal phosphorylation of cytoskeletal elements occurs in a variety of neuropathological conditions. In organophosphorus ester-induced delayed neurotoxicity (OPIDN) a dramatic increase in kinase mediated phosphorylation of cytoskeletal proteins precedes focal axonal swelling an...

To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that ...

Longitudinal axons transmit all signals between the brain and spinal cord. Their axon tracts through the brain stem are established by a simple set of pioneer axons with precise trajectories parallel to the floor plate. To identify longitudinal guidance mechanisms in vivo, the overall role of floor plate tissue and the specific roles ...

Neurons have efficient mechanisms for the transport of organelles and chemical substances in axons to the nerve terminals and back to the cell bodies. Enzymes involved in transmitter synthesis, peptide transmitters and their precursors are examples of macromolecules that are transported down the axon, ...

After focal cerebral infarction by occluding the middle cerebral artery (MCA) of the rat, the neuronal death occurred in the ipsilateral thalamic neurons, because axons of the thalamic neurons were injured by infarction and retrograde degeneration occurred in the thalamic neurons. However, cortical neurons adjacent to the infarction survived despite their ...

Prior investigations of traumatic axonal injury (TAI), and pharmacological treatments of TAI pathology, have focused exclusively on the role of myelinated axons, with no systematic observations directed towards unmyelinated axon pathophysiology. Recent electrophysiological evidence, however, indicates that unmyelinated ...

The cell body of a lesioned neuron must receive accurate and timely information on the site and extent of axonal damage, in order to mount an appropriate response. Specific mechanisms must therefore exist to transmit such information along the length of the axon from the lesion site to the cell body. Three distinct types of signals have been postulated to ...

The ultrastructural view of the axonal cytoskeleton as an extensively crosslinked network of neurofilaments (NFs) and other cytoskeletal polymers contrasts with the dynamic view suggested by axonal transport studies on cytoskeletal elements. Here we reconcile these perspectives by showing that neurons form a large NF network along ...

A major issue in the slow transport of cytoskeletal proteins is the form in which they are transported. We have investigated the possibility that unpolymerized as well as polymerized cytoskeletal proteins can be actively transported in axons. We report the active transport of highly diffusible ...

Successful axonal repair following injury is critical for nerve regeneration and functional recovery. Nerve repair relies on three functionally distinct events involving membrane trafficking. First, axonally transported vesicles accumulate, while others are generated at the cut end to restore a selective barrier to the severed ...

Polarized transport in neurons is fundamental for the formation of neuronal circuitry. A motor domain-containing truncated KIF5 (a kinesin-1) recognizes axonal microtubules, which are enriched in EB1 binding sites, and selectively accumulates at the tips of axons. However, it remains unknown what cue KIF5 recognizes to result in this ...

AbstractThe functional imaging of neuronal circuits of the central nervous system is crucial for phenotype screenings or investigations of defects in neurodegenerative disorders. Current techniques yield either low penetration depth, yield poor resolution, or are restricted by the age of the animals. Here, we present a novel ultramicroscopy protocol for fluorescence imaging and three-dimensional ...

... The long term goal of our research is to ... These qualitative experiments lent support to our ideas, but ... out the need for a quantitative assay method for ...

This paper simulates an axon with a region of reversed microtubule (MT) polarity, and investigates how the degree of polar mismatching in this region affects the formation of organelle traps in the axon. The model is based on modified Smith-Simmons equations governing molecular-motor-assisted transport in neurons. It is established ...

Feb 11, 1997... fluid and electrolyte homeostasis. Present experiments deal with axonal transport of neuropeptides by molecular motors via microtubules. ...

A model of retrograde axonal transport of neurotropic viruses is developed. The model accounts for active viral transport by dynein motors as well as for passive transport by diffusion; the destruction of the virus as it propagates toward the neuron soma is modeled utilizing a first-order decay rate process. The ...

1. The axonal transport of pulses of [3H]serotonin was studied in an axon of the serotonergic giant cerebral neurone (GCN) of Aplysia californica. 2. [3H]serotonin was transported as a discrete peak which was followed by a relatively low, smooth trail. 3. The peak broadened as it moved along the ...

Impaired axonal transport has been linked to the pathogenic processes of Alzheimer's disease (AD) in which axonal swelling and degeneration are prevalent. The development of non-invasive neuroimaging methods to quantitatively assess in vivo axonal transport deficits would be enormously valuable ...

Proteins vital to presynaptic function are synthesized in the neuronal perikarya and delivered into synapses via two modes of axonal transport. While membrane-anchoring proteins are conveyed in fast axonal transport via motor-driven vesicles, cytosolic proteins travel in slow axonal ...

Rabies virus is a neurotropic agent which spreads in the CNS via axonal transport. Previous studies had shown that this axonal transport through the brain could be inhibited by stereotaxic administration of colchicine; however, this inhibition was reversible. We describe here a method to enhance the duration of ...

Upon entry, neuroinvasive herpesviruses traffic from axon terminals to the nuclei of neurons resident in peripheral ganglia, where the viral DNA is deposited. A detailed analysis of herpes simplex virus type 1 (HSV-1) transport dynamics in axons following entry is currently lacking. Here, time lapse fluorescence microscopy was used to ...

Upon entry, neuroinvasive herpesviruses traffic from axon terminals to the nuclei of neurons resident in peripheral ganglia, where the viral DNA is deposited. A detailed analysis of herpes simplex virus type 1 (HSV-1) transport dynamics in axons following entry is currently lacking. Here, time lapse fluorescence microscopy was used to ...

Axonal transport is responsible for the movement of signals and cargo between nerve termini and cell bodies. Pathogens also exploit this pathway to enter and exit the central nervous system. In this study, we characterised the binding, endocytosis and axonal transport of an adenovirus (CAV-2) that preferentially ...

After intracranial inoculation, neurovirulent mouse hepatitis virus (MHV) strains induce acute inflammation, demyelination, and axonal loss in the central nervous system. Prior studies using recombinant MHV strains that differ only in the spike gene, which encodes a glycoprotein involved in virus-host cell attachment, demonstrated that spike mediates anterograde ...

Thermography is a very instructive method of showing the interaction between direct changes in heat radiation of the surface of the skin and its relation to reflex processes. Short reflex arcs, such as the axon reflex, and long reflex arcs, such as the flush phenomenon provoked by visceral cutaneous reflexes, can be illustrated by thermography. Reflex changes in skin ...

Zebrafish semaphorin 1b (sema Z1b) is a new member of the semaphorin family, related to mammalian sema D/III. It is expressed in rhombomeres three and five, and in the posterior half of newly formed somites which is avoided by ventrally extending motor axons. Embryos injected at the 1-2 cell stage with synthetic sema Z1b mRNA developed normally but many (63%) showed missing or ...

Conditional deletion of APC leads to marked disruption of cortical development and to excessive axonal branching of cortical neurons. However, little is known about the cell biological basis of this neuronal morphological regulation. Here we show that APC deficient cortical neuronal growth cones exhibit marked disruption of both microtubule and actin cytoskeleton. Functional ...

Trafficking and local translation of axonal mRNAs play a critical role in the development and function of this neuronal subcellular structural domain. In this report, we studied cytochrome c oxidase subunit IV (COXIV) mRNA trafficking into distal axons of primary superior cervical ganglia (SCG) neurons, and provided evidence that ...

Recently, we showed that Schwann cells transfer ribosomes to injured axons. Here, we demonstrate that Schwann cells transfer ribosomes to regenerating axons in vivo. For this, we used lentiviral vector-mediated expression of ribosomal protein L4 and eGFP to label ribosomes in Schwann cells. Two approaches were followed. First, we transduced Schwann cells ...

Neuregulin-1 has a key role in mediating signalling between axons and Schwann cells during development. A limitation to studying its role in adulthood is the embryonic lethality of global Nrg1 gene deletion. We used the Cre-loxP system to generate transgenic mice in which neuregulin-1 is conditionally ablated in the majority of small diameter and a proportion of large diameter ...

BackgroundIn addition to its well-known expression in dorsal telencephalic progenitor cells, where it regulates cell proliferation and identity, the transcription factor Pax6 is expressed in some ventral telencephalic cells, including many postmitotic neurons. Its functions in these cells are unknown.ResultsWe generated a new floxed allele of Pax6 and tested the consequences of a highly specific ...

Acetylcholine is transported along insect chemoreceptor axons at a rate of 12 to 13 centimeters per day after peripheral uptake of choline. Colchicine, vinblastine sulfate, and cytochalasin B all block transport, but transport continues in axons separated surgically from the cell body. These ...

Shaker K+ channels play an important role in modulating electrical excitability of axons. Recent work has demonstrated that the T1 tetramerization domain of Kv1.2 is both necessary and sufficient for targeting of the channel to the axonal surface [Gu, C., Jan, Y.N. & Jan, L.Y. (2003) Science,301, 646-649]. Here we use a related channel, Kv1.3, as a ...

In order to characterize differences in growth patterns of axons as they elongate toward their targets and during the initial stages of terminal arbor formation within the targets, we examined the primary visual system of fetal and newborn hamsters using three morphological methods: the Cajal-deCastro reduced silver method, the rapid Golgi technique, and anterograde ...

We studied axonal damage in Alzheimer's disease frontal cortex and hippocampus with a novel monoclonal antibody (SMI 312) against phosphorylated neurofilaments. This antibody immunolabeled, with great detail, the neuropil axonal network. In aged normal cases only a few pyramidal cell perikarya were immunostained. In Alzheimer's disease there was a two- to ...

Mitochondrial dysfunction plays a relevant role in the pathogenesis of neurological and neuromuscular diseases. Mitochondria may be involved as a primary defect of either the mtDNA or nuclear genome encoded subunits of the respiratory chain. These organelles have also been directly involved in the pathogenesis of Mendelian neurodegenerative disorders caused by mutations in nuclear-encoded proteins ...

Quantitative analyses of electron microscopic (EM) autoradiographs were used to identify the afferents from the dorsal cochlear nucleus in the central nucleus of the inferior colliculus (IC) in the cat. In order to localize the sources of radioactivity, material from axonal transport experiments was analyzed by means of a hypothetical grain procedure which ...

Peripheral nerve injury is sometimes followed by the development of persistent painful sensory disorders, such as dysaesthesia. The aetiology of these disorders is not clear, but abnormal behaviour of damaged axons at the injury site is likely to be involved. In this study, we quantified some ultrastructural characteristics that may be related to the ...

Based upon recent clinical findings, evidence exists that severe traumatic brain injury causes widespread axonal damage. In the clinical setting, it has been assumed that such axonal damage is the immediate consequence of traumatically induced tearing. However, in laboratory studies of minor head injury, evidence for primary traumatically induced ...

Phosphorylated and nonphosphorylated epitopes of neurofilament (NF) proteins are distributed in different regions of individual neurons. Immunocytochemical methods, with monoclonal antibodies directed against phosphorylated and nonphosphorylated NF, demonstrated nonphosphorylated NF in perikarya and proximal axonal segments of neurons in dorsal root ganglia, while ...

Neurons of the motor nerve net of Cyanea capillata were examined using video-enhanced DIC optics. A variety of organelles were visible within the axons and many were mobile. To quantify the movement organelles were divided into three classes (large, medium, and small) and the rates, direction, and types of movement displayed by the different particle types examined. The ...

Neurofilaments(NFs) represent the main space-filling elements of mature axons. NFs are transported on microtubule (MT) tracks along the axon at a slow rate of mm/day and thus form a dynamic cytoskeleton. During development, the optic nerve forms a sharp increase of caliber at about 150 ?m from the retinal excavation of the eye. Our key ...

After surgical section of the vomeronasal nerves the neurosensory cells in the vomeronasal epithelium die. Electron microscopy has been used to demonstrate that their axons, and synaptic terminals in the accessory olfactory bulb degenerate and are removed by phagocytic astroglia. The vacated postsynaptic sites in the accessory bulb persist, and are not re-innervated, either by ...

Retinal projections to visual centers in a marsupial mammal, the tammar wallaby (Macropus eugenii), have been investigated after an eye rotation prior to retinal innervation of the brain. Retinal topography to the superior colliculus and dorsal lateral geniculate nucleus was mapped by using laser lesions of the retina and horseradish peroxidase histochemistry. Despite the change in orientation of ...

ABSTRACT: BACKGROUND: The formation of the mammalian central nervous system requires the establishment of complex neural circuits between a diverse array of neuronal subtypes. Here we report that the proneural transcription factor Neurogenin2 (Ngn2) is crucial for the proper specification of cortical axon projections. RESULTS: The genetic loss of Ngn2 in mice results in fewer ...

BackgroundThe formation of the mammalian central nervous system requires the establishment of complex neural circuits between a diverse array of neuronal subtypes. Here we report that the proneural transcription factor Neurogenin2 (Ngn2) is crucial for the proper specification of cortical axon projections.ResultsThe genetic loss of Ngn2 in mice results in fewer callosal ...

Axon-guidance-pathway molecules are involved in connectivity and repair throughout life (beyond guiding brain wiring during fetal development). One study found that variations (single-nucleotide polymorphisms [SNPs]) in axon-guidance-pathway genes were predictive of three Parkinson�s disease (PD) outcomes (susceptibility, survival free of PD and age at ...

Recent studies have shown that the transport of microtubules (MTs) and neurofilaments (NFs) within the axon is rapid, infrequent, asynchronous, and bidirectional. Here, we used RNA interference to investigate the role of cytoplasmic dynein in powering these transport events. To reveal transport of MTs and NFs, we ...

Regulation of microtubule dynamics underlies many fundamental cellular mechanisms including cell division, cell motility, and transport. In neurons, microtubules play key roles in cell migration, axon outgrowth, control of axon and synapse growth, and the regulated transport of vesicles and structural components of ...

The capsids of neurotropic herpesviruses have the remarkable ability to move in specific directions within axons. By modulating bidirectional capsid transport to favor either retrograde (minus-end) or anterograde (plus-end) motion, these viruses travel to sensory ganglia or peripheral tissue at specific stages of infection. By using correlative motion ...

Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau overexpression diminishes axonal transport in several systems, but ...

BackgroundAlpha-synuclein is a presynaptic protein with a proposed role in neurotransmission and dopamine homeostasis. Abnormal accumulation of ?-synuclein aggregates in dopaminergic neurons of the substantia nigra is diagnostic of sporadic Parkinson's disease, and mutations in the protein are linked to early onset forms of the disease. The folded conformation of the protein ...

Traumatic axonal injury (TAI) following traumatic brain injury (TBI) remains a clinical problem for which no effective treatment exists. TAI was thought to involve intraaxonal changes that universally led to impaired axonal transport (IAT), disconnection and axonal bulb formation. However, recent, ...

PublishingGrouphttp://www.nature.com/naturemethods #12;populations may be labeled via stereotactic injection of viruses that effect retrograde axonal transport or diode laser) or by a mercury or xenon lamp filtered using a blue bandpass filter (e.g., HQ470/40X retrograde axonal transport and access to the nervous ...

Female Wistar rats were injected in the tongue with a small volume of 203Hg and were killed 2 weeks later. The lower brain stem with the hypoglossal nuclei was removed and sectioned in a cryostat. Autoradiography of freeze-dried sections showed labeling of both hypoglossal nuclei. The results are regarded as strong evidence of retrograde axonal transport ...

Retrograde axonal transport of phosphatidylcholine in the sciatic nerve has been demonstrated only after injection of lipid precursors into the cell body region. After microinjection (1 microliters) of (methyl-(3)H)choline chloride into the rat sciatic ne...

Retrograde axonal transport of phosphatidylcholine (PC) in the sciatic nerve has been demonstrated only after injection of lipid precursors into the cell body regions (Armstrong et al. 1985). icroinjection of [methyl-3H]choline into the sciatic nerve results in extensive incorpor...

Pattern reversal evoked potentials (PREPs), flash evoked potentials (FEPs), optic nerve axonal transport, and body temperature were measured in hooded rats treated with either saline or the formamidine insecticide/acaricide, chlordimeform (CDM). Rats rece...

Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone & Hiroyuki Kamiguchi1 Asymmetric elevation of the Ca21 concentration in the growth cone can mediate both membrane trafficking mediates growth cone attraction. Local photolysis of caged Ca21, together with CICR