Neuroscience 2005 Abstract
| Presentation Number: | 783.20 |
|---|---|
| Abstract Title: | Molecular mechanisms of spinal cord dysfunction and cell death in the spinal hyperostotic mouse: implications for the pathophysiology of human cervical spondylotic myelopathy. |
| Authors: |
Yu, W.*1
; Liu, T.1
; Baptiste, D. C.1
; Odrobina, E.2
; Stanisz, G. J.2
; Fehlings, M. G.1
1Divisions of Cell and Molecular Biology and Neurosurgery, Toronto Western Research Inst. and Krembil Neuroscience Centre, Toronto Western Hospital, Univ. Health Network, Toronto, Ontario, Canada, Toronto Western Hospital Research Inst., Toronto, Canada 2ON, Univ Toronto Ste 12-407, M5T 2S8, |
| Primary Theme and Topics |
Sensory and Motor Systems - Spinal Cord -- Injury and recovery |
| Secondary Theme and Topics | Neural Excitability, Synapses, and Glia: Cellular Mechanisms<br />- Neurotransmitters and Signaling Molecules<br />-- Amino acids: Intracellular signaling cascades |
| Session: |
783. Spinal Cord Injury: Models Poster |
| Presentation Time: | Tuesday, November 15, 2005 4:00 PM-5:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # SS50 |
| Keywords: | Fas, apoptosis, CSM, Spinal cord injury |
Ossification of the posterior longitudinal ligament of the spine (OPLL) results in a common form of spinal cord impairment in humans termed cervical spondylotic myelopathy (CSM). Although the etiology of spinal cord dysfunction in CSM is not well understood, evidence supports ischemia and compression as major underlying pathological events. To help clarify the pathomechanisms involved in CSM, we have utilized the spinal hyperostotic Tiptoe Walking Yoshimura (twy/twy) mouse, a naturally occuring autosomal recessive mutant with an abnormality in the nucleotide pyrophosphatase (Npps) gene, which develops multiple progressive calcifications at C1-C2 with progressive spinal cord compression. Twy/twy mice developed neurobehavioural abnormalities, which were quantified by footprint analysis. Magnetic resonance imaging (MRI) disclosed marked ossification of the soft tissues dorsal to the cord at C1-C2 with severe cord compression. In this study we demonstrate that relative to normal wildytpe control mice, compressed cervical spinal cord tissues derived from twy/twy mice were associated with a profound degree of neuronal and oligodendroglial apoptosis, increased expression of Fas and Fas ligand (FasL), elevated activation of caspase-9 and -3, and marked functional impairments. The results of this research provides novel evidence to support a key role for the Fas-mediated apoptotic cascade in the pathobiology of cell death and neurological dysfunction in the twy/twy mouse. Thus, the present data implicate these mechanisms in the pathobiology of human CSM, which may lead to novel targets for therapeutic intervention following decompressive surgery.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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