Molecular mechanisms of neural plasticity after spinal cord injury in the lamprey central nervous system
| dc.contributor.advisor | Morgan, Jennifer Rebecca | |
| dc.creator | Lau, Billy You Bun | en |
| dc.date.accessioned | 2013-11-12T20:17:32Z | en |
| dc.date.accessioned | 2017-05-11T22:36:46Z | |
| dc.date.available | 2017-05-11T22:36:46Z | |
| dc.date.issued | 2012-08 | en |
| dc.date.submitted | August 2012 | en |
| dc.date.updated | 2013-11-12T20:17:32Z | en |
| dc.description | text | en |
| dc.description.abstract | Spinal cord injury induces anatomical plasticity throughout the nervous system, including distant locations in the brain. Several types of injury-induced plasticity have been identified, such as neurite sprouting, axon regeneration and synaptic remodeling. However, the molecular mechanisms involved in anatomical plasticity after injury are unclear, as is the extent to which injury-induced plasticity in the brain is conserved across vertebrate lineages. Here, I used lampreys to identify the molecular mechanisms in mediating anatomical plasticity, because lampreys undergo anatomical plasticity and functional recovery after a complete spinal cord transection. Due to their robust roles in neurite outgrowth during neuronal development, I examined synapsin and synaptotagmin for their potential involvement in anatomical plasticity after injury. I found increased synapsin I mRNA throughout the lamprey brain as well as increased protein levels of synapsin I, phospho-synapsin (Ser 9) and synaptotagmin in the lamprey hindbrain after injury, suggestive of anatomical plasticity. Anatomical plasticity was confirmed at the ultrastructural level, where I found increased neurite density in the lamprey hindbrain after injury. Other molecular mechanisms that promote anatomical plasticity have been previously identified, such as cyclic AMP (cAMP). However, the cellular mechanisms and the molecular targets of cAMP in mediating anatomical plasticity are unclear. My investigation of cAMP revealed that cAMP enhanced the number of regenerated axons beyond the lesion site in lampreys after injury. For the first time in a spinal cord injury model, I found cAMP prevented the death of axotomized neurons that normally have a high tendency to die after injury. In addition, cAMP promoted more regenerating axons to re-grow in straighter paths rather than turning rostrally towards the brain stem. At the molecular level, I found cAMP increased synaptotagmin protein level at the regenerating axon tips, suggestive of enhanced axon elongation. Taken together, my results show that neurite sprouting in the brain and the cAMP-enhanced axon regeneration are conserved responses in vertebrates after spinal cord injury. In addition, my results suggest that at least some developmental pathways are activated during injury-induced and cAMP-enhanced anatomical plasticity. Further understanding of these pathways will provide insights for improving recovery after spinal cord injury. | en |
| dc.description.department | Cellular and Molecular Biology | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.uri | http://hdl.handle.net/2152/22128 | en |
| dc.language.iso | en_US | en |
| dc.subject | Axon regeneration | en |
| dc.subject | Axon tip | en |
| dc.subject | Cyclic AMP | en |
| dc.subject | Cell death | en |
| dc.subject | Neurite sprouting | en |
| dc.subject | Petromyzon marinus | en |
| dc.subject | Phospho-synapsin | en |
| dc.subject | SV2 | en |
| dc.subject | Synapsin | en |
| dc.subject | Synaptotagmin | en |
| dc.title | Molecular mechanisms of neural plasticity after spinal cord injury in the lamprey central nervous system | en |