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Updated: Feb 11, 2026
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Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
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RhoA activation in axotomy-induced neuronal death
Guixin Zhang1, Jianli Hu1, William Rodemer1
1Shriners Hospitals Pediatric Research Center (Center for Neural Repair and Rehabilitation), USA.
Experimental Neurology
|May 2, 2018
Summary
Spinal cord injury (SCI) triggers neuronal death and inhibits axon regeneration. This study reveals that RhoA activation in lamprey neurons after SCI correlates with cell death, suggesting RhoA
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Mammalian spinal cord injury (SCI) prevents axon regeneration due to inhibitory factors and loss of intrinsic growth capacity.
- Lamprey reticulospinal neurons show varying regeneration abilities and delayed apoptosis after SCI, suggesting converging pathways for cell death and regeneration inhibition.
- RhoA activation inhibits axon growth, but its role in retrograde neuronal death post-axotomy is unclear.
Purpose of the Study:
- To investigate the role of RhoA in retrograde neuronal death following spinal cord injury in lamprey.
- To correlate RhoA mRNA expression and activation with apoptosis signaling in identified reticulospinal neurons post-SCI.
Main Methods:
- Cloned lamprey RhoA and analyzed its mRNA expression and activation state.
- Utilized fluorescently labeled inhibitors of caspase activation (FLICA) to identify apoptotic neurons.
- Correlated RhoA expression and activation with FLICA labeling in reticulospinal neurons at various time points after spinal cord transection.
Main Results:
- RhoA mRNA was detected in severed axon tips within a day post-SCI and upregulated in pre-apoptotic neuronal perikarya starting at 5 days.
- RhoA was continuously active in apoptotic neurons (FLICA-positive) for up to 9 weeks post-SCI.
- Neurons with regenerated axons showed minimal FLICA positivity, indicating reduced apoptosis.
Conclusions:
- RhoA activation plays a significant role in triggering retrograde neuronal death after spinal cord injury in lamprey.
- RhoA may represent a convergence point for mechanisms inhibiting both axon regeneration and neuronal survival following axotomy.
- Targeting RhoA could offer a therapeutic strategy for enhancing neuronal survival and axon regeneration after SCI.
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