Axon repulsion during peripheral nerve segmentation

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 131-139 ◽  
Author(s):  
Roger J. Keynes ◽  
Karen F. Jaques ◽  
Geoffrey M. W. Cook
Keyword(s):  
Dorsal Root ◽  
Grey Matter ◽  
Growth Cones ◽  
Spinal Nerve ◽  
Chick Embryos ◽  
Posterior Half ◽  
Similar Activity ◽  
Sensory Axons ◽  
Axon Repulsion

The guidance of axons during embryonic development is likely to involve both adhesive and repulsive interactions between growth cones and their environment. We are characterising the role and mechanism of repulsion during the segmental outgrowth of motor and sensory axons in the somite mesoderm of chick embryos. Axons are confined to the anterior half of each somite by the expression in the posterior half of a glycoconjugate system (48×103Mr and 55×103Mr) that causes the collapse of dorsal root ganglion growth cones when applied in vitro. Enzymatic cleavage of this fraction with specific combinations of endo- and exoglycosidases removes collapse activity, suggesting that carbohydrate residues are involved in the execution of collapse. A similar activity is also detectable in normal adult grey matter, suggesting roles for repulsion beyond the development of spinal nerve segmentation.

Similar Electrophysiological Changes in Axotomized and Neighboring Intact Dorsal Root Ganglion Neurons

2003 ◽  
Vol 89 (3) ◽  
pp. 1588-1602 ◽  
Author(s):  
Chao Ma ◽  
Yousheng Shu ◽  
Zheng Zheng ◽  
Yong Chen ◽  
Hang Yao ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Receptive Fields ◽  
Input Resistance ◽  
Spinal Nerve ◽  
Dorsal Root Ganglion Neurons ◽  
Drg Neurons ◽  
Ganglion Neurons

We investigated electrophysiological changes in chronically axotomized and neighboring intact dorsal root ganglion (DRG) neurons in rats after either a peripheral axotomy consisting of an L5 spinal nerve ligation (SNL) or a central axotomy produced by an L5 partial rhizotomy (PR). SNL produced lasting hyperalgesia to punctate indentation and tactile allodynia to innocuous stroking of the foot ipsilateral to the injury. PR produced ipsilateral hyperalgesia without allodynia with recovery by day 10. Intracellular recordings were obtained in vivo from the cell bodies (somata) of axotomized and intact DRG neurons, some with functionally identified peripheral receptive fields. PR produced only minor electrophysiological changes in both axotomized and intact somata in L5 DRG. In contrast, extensive changes were observed after SNL in large- and medium-sized, but not small-sized, somata of intact (L4) as well as axotomized (L5) DRG neurons. These changes included (in relation to sham values) higher input resistance, lower current and voltage thresholds, and action potentials with longer durations and slower rising and falling rates. The incidence of spontaneous activity, recorded extracellularly from dorsal root fibers in vitro, was significantly higher (in relation to sham) after SNL but not after PR, and occurred in myelinated but not unmyelinated fibers from both L4 (9.1%) and L5 (16.7%) DRGs. We hypothesize that the changes in the electrophysiological properties of axotomized and intact DRG neurons after SNL are produced by a mechanism associated with Wallerian degeneration and that the hyperexcitability of intact neurons may contribute to SNL-induced hyperalgesia and allodynia.

scholarly journals cGMP-mediated signaling via cGKIα is required for the guidance and connectivity of sensory axons

2002 ◽  
Vol 159 (3) ◽  
pp. 489-498 ◽  
Author(s):  
Hannes Schmidt ◽  
Matthias Werner ◽  
Paul A. Heppenstall ◽  
Mechthild Henning ◽  
Margret I. Moré ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
In Vitro Studies ◽  
Axonal Guidance ◽  
Dorsal Funiculus ◽  
Spinal Cord Neurons ◽  
Sensory Axons ◽  
Deficient Mice

Previous in vitro studies using cGMP or cAMP revealed a cross-talk between signaling mechanisms activated by axonal guidance receptors. However, the molecular elements modulated by cyclic nucleotides in growth cones are not well understood. cGMP is a second messenger with several distinct targets including cGMP-dependent protein kinase I (cGKI). Our studies indicated that the α isoform of cGKI is predominantly expressed by sensory axons during developmental stages, whereas most spinal cord neurons are negative for cGKI. Analysis of the trajectories of axons within the spinal cord showed a longitudinal guidance defect of sensory axons within the developing dorsal root entry zone in the absence of cGKI. Consequently, in cGKI-deficient mice, fewer axons grow within the dorsal funiculus of the spinal cord, and lamina-specific innervation, especially by nociceptive sensory neurons, is strongly reduced as deduced from anti-trkA staining. These axon guidance defects in cGKI-deficient mice lead to a substantial impairment in nociceptive flexion reflexes, shown using electrophysiology. In vitro studies revealed that activation of cGKI in embryonic dorsal root ganglia counteracts semaphorin 3A–induced growth cone collapse. Our studies therefore reveal that cGMP signaling is important for axonal growth in vivo and in vitro.

scholarly journals Valproic Acid Accelerates Neural Outgrowth during Dorsal Root Ganglia Neurogenesis In Vitro

2019 ◽  
pp. 149-162
Author(s):  
Wiens D ◽  
Bergan H ◽  
Walter OS ◽  
McGinley A ◽  
Ahlrichs B
Keyword(s):  
Valproic Acid ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Trichostatin A ◽  
Time Lapse ◽  
Growth Cones ◽  
Autism Spectrum ◽  
Neuronal Structure ◽  
And Behavior

Background: Valproic acid (VPA) is an anti-convulsant drug used to treat seizures and a variety of neural pathologies. Studies have shown that VPA exposure in rodent embryos leads to behavioral characteristics similar to those in humans with autism spectrum disorder (ASD). Utilizing this rodent model of ASD, research has led to a recognized mechanism of action of VPA involving brain overgrowth and hyperconnectivity, likely caused by epigenetic alteration of gene expression through inhibition of histone deacetylases.Objective: To gain further insight concerning this mechanism we modeled the development of neural connectivity at the cellular level.Method: We cultured dorsal root ganglia (DRGs) taken from eight-day old chick embryos in a range of VPA concentrations and investigated aspects of neuronal structure and behavior. DRGs were cultured 48 hours, fixed, and immunostained to reveal the locations of neural networks with synaptic vesicles.Results: We found a concentration-dependant relationship with a significant increase in neurite length in VPA concentrations of 1 and 2 mM, and the effect was still present though weaker at 4 and 6 mM. Trichostatin A (TSA), another histone deacetylase inhibitor, caused similar responses. To further characterize the effects, we carried out time-lapse imaging of growth cones of extending neurites. We found that VPA increased the area changing activity of growth cones, augmenting their exploratory capabilities, along with significantly enhancing overall advancement, thus increasing the ability to extend and form synapses. The average total of stained synaptic areas surrounding each cultured DRG was significantly increased in 6 mM VPA, but not significantly at the lower concentrations compared to controls.Conclusion: Our results show that VPA, at 1 mM and higher concentrations increases growth cone activity, and increases the number of neurites and their extension, a neurotrophic effect. It also increases synaptogenesis at 6 mM, supporting the theory of developmental neuronal overgrowth.

Neurotoxicity of Seven MEIC Chemicals Evaluated in Organotypic Cultures of Chick Embryonic Dorsal Root Ganglia

1997 ◽  
Vol 25 (3) ◽  
pp. 303-309
Author(s):  
Václav Mandys ◽  
Katerina Jirsová ◽  
Jirí Vrana
Keyword(s):  
Toxic Effect ◽  
Neurite Outgrowth ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Growth Parameters ◽  
In Vitro Cytotoxicity ◽  
Organotypic Cultures ◽  
Response Curves ◽  
Agar Culture

The neurotoxic effects of seven selected Multicenter Evaluation of In Vitro Cytotoxicity programme chemicals (methanol, ethanol, isopropanol, sodium chloride, potassium chloride, iron [II] sulphate and chloroform) were evaluated in organotypic cultures of chick embryonic dorsal root ganglia (DRG), maintained in a soft agar culture medium. Two growth parameters of neurite outgrowth from the ganglia — the mean radial length of neurites and the area of neurite outgrowth — were used to evaluate the toxicities of the chemicals. Dose-dependent decreases of both parameters were observed in all experiments. IC50 values (the concentration causing 50% inhibition of growth) were calculated from the dose-response curves established at three time-points during culture, i.e. 24, 48 and 72 hours. The lowest toxic effect was observed in cultures exposed to methanol (the IC50 ranging from 580mM to 1020mM). The highest toxic effect was observed in cultures exposed to iron (II) sulphate (the IC50 ranging from 1.2mM to 1.7mM). The results of other recent experiments suggest that organotypic cultures of DRG can be used during in vitro studies on target organ toxicity within the peripheral nervous system. Moreover, these cultures preserve the internal organisation of the tissue, maintain intercellular contacts, and thus reflect the in vitro situation, more precisely than other cell cultures.

Biochemical and pharmacokinetic characterisation of two PEGylated variants of dipetarudin

2009 ◽  
Vol 102 (09) ◽  
pp. 454-459 ◽  
Author(s):  
Anne Koehler ◽  
Goetz Nowak ◽  
Mercedes López
Keyword(s):  
Gel Filtration ◽  
Pharmacokinetic Profile ◽  
Peripheral Compartment ◽  
Therapeutic Application ◽  
Similar Activity ◽  
Elimination Half ◽  
K 12 ◽  
Extravascular Compartment

SummaryDipetarudin was coupled to polyethylene glycol (PEG)-5000 residues in order to improve its pharmacokinetic profile and to enhance its anticoagulant efficacy. The resulting compounds, mono-and di-PEGylated dipetarudin were purified by gel filtration. Mono-PEGylated dipetarudin exhibited similar activity like its non-conjugated equivalent both in vitro and in vivo. However, di-PEGylated dipetarudin showed longer distribution and elimination half-lives and higher area under the time-concentration curve in comparison with the unmodified inhibitor which may be attributed to decreased renal clearance. Futhermore, ratio k 12/k 21 decreased when the number of PEG chains coupled to dipetarudin increased. It means that the intercompartment transfer of dipetarudin, characterised by a fast distribution and a high retention in the peripheral compartment, is reverted by coupling to PEG. Thus, the transfer of mono-PEGylated dipetarudin between these compartments is similar in both senses and the transfer of di-PEGylated dipetarudin is slower from vascular to extravascular compartment than vice versa. Our results show that di-PEGylated dipetarudin produces a better and longer anticoagulant effect than unmodified dipetarudin which is a desirable attribute for future therapeutic application.

Continuation of fast axonal transport in regenerating axons in vitro

1979 ◽  
Vol 57 (11) ◽  
pp. 1251-1255
Author(s):  
M. A. Bisby ◽  
C. E. Hilton
Keyword(s):  
Sciatic Nerve ◽  
Vagus Nerve ◽  
Axonal Transport ◽  
Nerve Injury ◽  
Axon Regeneration ◽  
Free Medium ◽  
Fast Axonal Transport ◽  
Sensory Axons

A previous study by McLean and co-workers reported that regenerating axons of the rabbit vagus nerve were unable to sustain axonal transport in vitro for several months after nerve injury. In contrast, we found that sensory axons of the rat sciatic nerve were able to transport 3H-labeled protein into their regenerating portions distal to the site of injury within a week after injury when placed in vitro. Transport in vitro was not significantly less than transport in axons maintained in vivo for the same period. Transport occurred in the medium that was used by the McLean group, but was significantly reduced in calcium-free medium. When axon regeneration was delared, only small amounts of activity were present in the nerve distal to the site of injury, showing that labeled protein normally present in that part of the nerve was associated with axons and was not a result of local precursor uptake by nonneural elements in the sciatic nerve. We were not able to explain the failure of McLean and co-workers to demonstrate transport in vitro in regenerating vagus nerve, but we conclude that there is no general peculiarity of growing axons that makes them unable to sustain transport in vitro.

scholarly journals STUDIES OF THE DEGENERATION AND REGENERATION OF AXIS CYLINDERS IN VITRO

1913 ◽  
Vol 17 (2) ◽  
pp. 182-191 ◽  
Author(s):  
Ragnvald Ingebrigtsen
Keyword(s):  
Spinal Cord ◽  
Degenerative Changes ◽  
Spinal Ganglia ◽  
Chick Embryos

1. The brains of chick embryos, of cats six weeks old, of rabbits two months old, and of dogs three weeks old, when cultivated in vitro, develop long filaments which, according to their growth and their anatomical and tinctorial characters, must be considered as true axis cylinders. 2. Similar structures develop from spinal ganglia of rabbits seven months old, and from the spinal cord of cats six weeks old, and of rabbits two months old. 3. When severed from their origin by section these threads undergo degenerative changes which do not appear after nine hours, but which are seen after twenty hours, and continue until in the course of the following two days the thread degenerates completely. 4. After twenty hours the development of new axis cylinders from the central part of the cut fibers is observed.

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