cGMP promotes neurite outgrowth and growth cone turning and improves axon regeneration on spinal cord tissue in combination with cAMP

2009 ◽  
Vol 1294 ◽  
pp. 12-21 ◽  
Author(s):  
Andrew J. Murray ◽  
Andrew G. Peace ◽  
Derryck A. Shewan
Keyword(s):  
Spinal Cord ◽  
Neurite Outgrowth ◽  
Growth Cone ◽  
Axon Regeneration ◽  
Spinal Cord Tissue

scholarly journals EphA4 Obstructs Spinal Cord Neuron Regeneration by Promoting Excessive Activation of Astrocytes

2021 ◽  
Author(s):  
Xiaogang Chen ◽  
Lin Zhang ◽  
Fu Hua ◽  
Yu Zhuang ◽  
Huan Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Neurotrophic Factors ◽  
Cellular Localization ◽  
Axon Regeneration ◽  
Chondroitin Sulphate ◽  
Cortical Cell ◽  
Inflammatory Factors ◽  
Cord Injury

AbstractStudies have found that molecular targets that regulate tissue development are also involved in regulating tissue regeneration. Erythropoietin-producing hepatocyte A4 (EphA4) not only plays a guiding role in neurite outgrowth during the development of the central nervous system (CNS) but also induces injured axon retraction and inhibits axon regeneration after spinal cord injury (SCI). EphA4 targets several ephrin ligands (including ephrin-A and ephrin-B) and is involved in cortical cell migration, axon guidance, synapse formation and astrocyte function. However, how EphA4 affects axon regeneration after SCI remains unclear. This study focuses on the effect and mechanism of EphA4-regulated astrocyte function in neuronal regeneration after SCI. Our research found that EphA4 expression increased significantly after SCI and peaked at 3 days post-injury; accordingly, we identified the cellular localization of EphA4 and ephrin-B ligands in neurons and astrocytes after SCI. EphA4 was mainly expressed on the surface of neurons, ephrin-B1 and ephrin-B3 were mainly localized on astrocytes, and ephrin-B2 was distributed on both neurons and astrocytes. To further elucidate the effect of EphA4 on astrocyte function after SCI, we detected the related cytokines secreted by astrocytes in vivo. We found that the levels of neurotrophic factors including nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) increased significantly after SCI (NGF peaked at 3 days and bFGF peaked at 7 days); the expression of laminin and fibronectin increased gradually after SCI; the expression of inflammatory factors [interleukin (IL)-1β and IL-6] increased significantly from 4 h to 7 days after SCI; and the levels of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and chondroitin sulphate proteoglycan (CSPG), the main component of glial scars, both peaked at 7 days after SCI. Using a damaged astrocyte model in vitro, we similarly found that the levels of related cytokines increased after injury. Consequently, we observed the effect of damaged astrocytes on neurite outgrowth and regeneration, and the results showed that damaged astrocytes hindered neurite outgrowth and regeneration; however, the inhibitory effect of injured astrocytes on neurite regeneration was reduced following ephrin-B receptor knockdown or inflammatory inhibition at 24 h after astrocyte injury. Our results showed that EphA4 regulates the secretion of neurotrophic factors, adhesion molecules, inflammatory factors and glial scar formation by binding with the ligand ephrin-B located on the surface of astrocytes. EphA4 affects neurite outgrowth and regeneration after SCI by regulating astrocyte function.

scholarly journals Complement Protein C1q Modulates Neurite Outgrowth In Vitro and Spinal Cord Axon Regeneration In Vivo

2015 ◽  
Vol 35 (10) ◽  
pp. 4332-4349 ◽  
Author(s):  
S. L. Peterson ◽  
H. X. Nguyen ◽  
O. A. Mendez ◽  
A. J. Anderson
Keyword(s):  
Spinal Cord ◽  
Neurite Outgrowth ◽  
Axon Regeneration ◽  
Complement Protein

scholarly journals Oncomodulin derived from regeneration-associated macrophages in dorsal root ganglia promotes axon regeneration in the spinal cord

2021 ◽  
Author(s):  
Min Kwon ◽  
Yeojin Seo ◽  
Hana Cho ◽  
Jihye Choi ◽  
Hyung Soon Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neurite Outgrowth ◽  
Dorsal Root Ganglia ◽  
Axonal Regeneration ◽  
Dorsal Root ◽  
Axon Regeneration ◽  
Signal Sequence ◽  
Drg Neurons ◽  
Cord Injury

Preconditioning peripheral nerve injury enhances axonal regeneration of dorsal root ganglia (DRG) neurons in part by driving pro-regenerative perineuronal macrophage activation. How these regeneration-associated macrophages influence the neuronal capacity of axon regeneration remains elusive. The present study reports that oncomodulin (ONCM) is an effector molecule derived from the regeneration-associated macrophages. ONCM was highly upregulated in DRG macrophages following preconditioning injury and necessary for the preconditioning-induced neurite outgrowth. ONCM-deficient macrophages failed to generate neurite outgrowth activity of the conditioned medium in the in vitro model of neuron-macrophage interaction. CCL2/CCR2 signaling is an upstream regulator of ONCM since the ONCM upregulation was dependent on CCR2 and CCL2 overexpression-mediated conditioning effects were attenuated in ONCM-deficient mice. Direct application of ONCM potently increased neurite outgrowth in cultured DRG neurons by activating a distinct gene set, particularly neuropeptide-related genes. AAV-mediated overexpression of ONCM construct with the signal sequence increased neuronal secretion of ONCM and enhanced neurite outgrowth in an autocrine manner. For a clinically relevant approach, we developed a nanogel-mediated system for localized delivery of recombinant ONCM to DRG tissue. Electrostatic encapsulation of ONCM by a reducible epsilon-poly(L-lysine)-nanogel (REPL-NG) resulted in a slow release of ONCM allowing sustained bioactivity. Intraganglionic injection of REPL-NG/ONCM complex achieved a remarkable long-range axonal regeneration beyond spinal cord lesion, surpassing the extent expected from the preconditioning effects. The NG-mediated ONCM delivery could be exploited as a therapeutic strategy for promoting sensory axon regeneration following spinal cord injury.

scholarly journals Overexpression of Reticulon 3 enhances CNS axon regeneration and functional recovery after injury

2021 ◽  
Author(s):  
Zubair Ahmed ◽  
Sharif Alhajlah ◽  
Adam Thompson
Keyword(s):  
Spinal Cord ◽  
Optic Nerve ◽  
Neurite Outgrowth ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

CNS neurons are generally incapable of regenerating their axons after injury due to several intrinsic and extrinsic factors, including the presence of axon growth inhibitory molecules. One such potent inhibitor of CNS axon regeneration is Reticulon (RTN) 4 or Nogo-66. Here, we focused on RTN3 as its contribution in CNS axon regeneration is currently unknown. We found that RTN3 expression correlated with an axon regenerative phenotype in dorsal root ganglion neurons (DRGN) after injury to the dorsal columns, a model of spinal cord injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. Knockdown of protrudin however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo. Moreover, overexpression of RTN3 in a second model of CNS injury, the optic nerve crush injury model, enhanced retinal ganglion cell (RGC) survival, disinhibited neurite outgrowth in vitro and survival and axon regeneration in vivo, an effect that was also dependent on protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.

Retinoic acid as a chemoattractant for cultured embryonic spinal cord neurons of the African Clawed Frog, Xenopus laevis

2017 ◽  
Vol 95 (9) ◽  
pp. 653-661 ◽  
Author(s):  
C.D. Rand ◽  
G.E. Spencer ◽  
R.L. Carlone
Keyword(s):  
Spinal Cord ◽  
Retinoic Acid ◽  
Xenopus Laevis ◽  
Neurite Outgrowth ◽  
Growth Cone ◽  
Receptor Subtype ◽  
Spinal Cord Neurons ◽  
African Clawed Frog ◽  
Embryonic Spinal Cord ◽  
Clawed Frog

Retinoic acid (RA), an active metabolite of vitamin A, is important for neural development and regeneration and can induce neurite outgrowth. It may also act as a guidance molecule by attracting neurite processes during outgrowth. In the African Clawed Frog (Xenopus laevis (Daudin, 1802)), RA has been shown to play an important role in the development of the anterior–posterior axis. However, whether RA can act as a trophic or tropic molecule on embryonic neurons of this species has not been determined. In this study, we investigated the effects of two retinoid isomers, all-trans retinoic acid (atRA) and 9-cis retinoic acid (9-cisRA), on cultured embryonic spinal cord neurons of X. laevis. Both isomers significantly enhanced neurite outgrowth compared with the vehicle control. In addition, atRA induced growth cone turning, which was blocked with a retinoic acid receptor (RAR) antagonist, selective for the β receptor subtype. Immunostaining also revealed RAR immunoreactivity in the neurites and growth cones of these cells. Interestingly, the 9-cisRA isomer also induced significant growth cone turning and this response was inhibited by a retinoid X receptor (RXR) pan-antagonist. Overall, we have provided evidence for both trophic and chemotropic actions of two naturally occurring retinoid isomers on Xenopus embryonic spinal cord neurons in culture.

scholarly journals Overexpression of Reticulon 3 Enhances CNS Axon Regeneration and Functional Recovery after Traumatic Injury

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2015
Author(s):  
Sharif Alhajlah ◽  
Adam M Thompson ◽  
Zubair Ahmed
Keyword(s):  
Spinal Cord ◽  
Optic Nerve ◽  
Neurite Outgrowth ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

CNS neurons are generally incapable of regenerating their axons after injury due to several intrinsic and extrinsic factors, including the presence of axon growth inhibitory molecules. One such potent inhibitor of CNS axon regeneration is Reticulon (RTN) 4 or Nogo-A. Here, we focused on RTN3 as its contribution to CNS axon regeneration is currently unknown. We found that RTN3 expression correlated with an axon regenerative phenotype in dorsal root ganglion neurons (DRGN) after injury to the dorsal columns, a well-characterised model of spinal cord injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. Knockdown of protrudin, however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo. Moreover, overexpression of RTN3 in a second model of CNS injury, the optic nerve crush injury model, enhanced retinal ganglion cell (RGC) survival, disinhibited neurite outgrowth in vitro and survival and axon regeneration in vivo, an effect that was also dependent on protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.

scholarly journals AxonTracer: a novel ImageJ plugin for automated quantification of axon regeneration in spinal cord tissue

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Akash Patel ◽  
Zhongzhi Li ◽  
Philip Canete ◽  
Hans Strobl ◽  
Jennifer Dulin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Axon Regeneration ◽  
Spinal Cord Tissue ◽  
Automated Quantification ◽  
Imagej Plugin
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