Local calcium-dependent mechanisms determine whether a cut axonal end assembles a retarded endbulb or competent growth cone

Kamber, Dotan; Erez, Hadas; Spira, Micha Ε.

doi:10.1016/j.expneurol.2009.05.004

Cited by 71 publications

(57 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…35,60,[69][70][71][72] Thus, membrane depolarization may have long-lasting effects on neuron survival and axon growth because it rapidly initiates re-sealing of the cell membrane 72,73 and growth cone creation, a process also dependent on cellular levels of Ca 2 + . 74,75 The higher axon count reported here with acute stimulation of the transplanted cells supports this idea (Fig. 1).…”

Section: Electrical Stimulation Increased Motoneuron Survival and Axosupporting

confidence: 80%

Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

Grumbles

Liu

Thomas

et al. 2013

Journal of Neurotrauma

View full text Add to dashboard Cite

Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation.

show abstract

Section: Electrical Stimulation Increased Motoneuron Survival and Axosupporting

confidence: 80%

Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

Grumbles

Liu

Thomas

et al. 2013

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…These signals persist well beyond the large damage-induced calcium transients studied previously that last for only a few minutes following axotomy. The immediate signal is known to be important for efficient regeneration, is dependent on both external and internal calcium sources (Gitler and Spira, 1998;Chierzi et al, 2005;Ghosh-Roy et al, 2010), and modulates critical microtubule reorganization (Kamber et al, 2009). Here, we found that this immediate signal was partially dependent on UNC-68/RyR activity, as shown in Figure 3A, C. By contrast, the prolonged calcium signal over the 1-5 h following axotomy was completely eliminated in unc-68 mutants (Fig.…”

Section: Discussionmentioning

confidence: 48%

Neuronal Regeneration inC. elegansRequires Subcellular Calcium Release by Ryanodine Receptor Channels and Can Be Enhanced by Optogenetic Stimulation

et al. 2014

View full text Add to dashboard Cite

Regulated calcium signals play conserved instructive roles in neuronal repair, but how localized calcium stores are differentially mobilized, or might be directly manipulated, to stimulate regeneration within native contexts is poorly understood. We find here that localized calcium release from the endoplasmic reticulum via ryanodine receptor (RyR) channels is critical in stimulating initial regeneration following traumatic cellular damage in vivo. Using laser axotomy of single neurons in Caenorhabditis elegans, we find that mutation of unc-68/RyR greatly impedes both outgrowth and guidance of the regenerating neuron. Performing extended in vivo calcium imaging, we measure subcellular calcium signals within the immediate vicinity of the regenerating axon end that are sustained for hours following axotomy and completely eliminated within unc-68/RyR mutants. Finally, using a novel optogenetic approach to periodically photostimulate the axotomized neuron, we can enhance its regeneration. The enhanced outgrowth depends on both amplitude and temporal pattern of excitation and can be blocked by disruption of UNC-68/RyR. This demonstrates the exciting potential of emerging optogenetic technology to beneficially manipulate cell physiology in the context of neuronal regeneration and indicates a link to the underlying cellular calcium signal. Taken as a whole, our findings define a specific localized calcium signal mediated by RyR channel activity that stimulates regenerative outgrowth, which may be dynamically manipulated for beneficial neurotherapeutic effects.

show abstract

“…However, even in regeneration-competent class IV neurons, only about half of the injured dendrites are able to regenerate, suggesting that other factors in addition to neuronal growth capacity might be involved in dendritic regenerative responses. For example, it would be interesting to see whether the focal dendriotomy triggers consistent injury signals, such as calcium influx as observed after axotomy (McNeil and Kirchhausen 2005;Kamber et al 2009;Ghosh-Roy et al 2010). Nevertheless, the establishment of an efficient dendriotomy procedure should facilitate the investigation of these and other issues related to dendrite regeneration.…”

Section: Dendrite Regenerationmentioning

confidence: 99%

No simpler than mammals: axon and dendrite regeneration in Drosophila: Figure 1.

Nawabi

Zukor²,

He³

2012

Genes Dev.

View full text Add to dashboard Cite

Despite important progress made in understanding the mechanisms of axon regeneration, how a neuron responds to an injury and makes a regenerative decision remains unclear. In this issue of Genes & Development, Song and colleagues (pp. 1612–1625) investigate axonal and dendritic regeneration in the Drosophila peripheral nervous system (PNS). With some mechanisms shared with mammals, this study reveals surprisingly complicated regenerative responses in terms of cell type, developmental stage, and mechanism specificity. With forward genetic potential, such invertebrates should be powerful in dissecting the cellular and molecular control of neuronal repair.

show abstract

Local calcium-dependent mechanisms determine whether a cut axonal end assembles a retarded endbulb or competent growth cone

Cited by 71 publications

References 62 publications

Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

Neuronal Regeneration inC. elegansRequires Subcellular Calcium Release by Ryanodine Receptor Channels and Can Be Enhanced by Optogenetic Stimulation

No simpler than mammals: axon and dendrite regeneration in Drosophila: Figure 1.

Contact Info

Product

Resources

About