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Caspase inhibition attenuates transection-induced oligodendrocyte apoptosis in the developing chick spinal cord
Christopher B McBride1, Lowell T McPhail, Jacqueline L Vanderluit
1ICORD (International Collaboration On Repair Discoveries), University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. mcbride@icord.org
Abstract:
A developmental model of spinal cord injury in the embryonic chick was specifically developed to characterize the involvement of caspases in injury-induced oligodendrocyte apoptosis remote from the lesion and the ability of caspase inhibitors to attenuate this process. Developmental apoptosis in the cervical spinal cord increased within the white matter between embryonic days 13 and 18, the period of myelination of this region. Spinal cord transection during this period induced a rapid increase in apoptotic cells in the ventral and lateral white matter over several millimeters caudal to the injury. Immunostaining identified large numbers of these cells as oligodendrocytes. Catalytic activity assays and immunostaining demonstrated caspase-3-like but not caspase-1-like activity to be involved in this apoptotic response. In vivo application of specific caspase inhibitors significantly attenuated transection-induced apoptosis. Thus, we describe a developmental period during which spinal oligodendrocytes exhibited a heightened, caspase-dependent sensitivity to transection-induced apoptosis that is attenuated by caspase inhibition.
Insights
Spinal cord injury in embryonic chicks triggers caspase-dependent oligodendrocyte apoptosis. Caspase inhibitors effectively reduce this cell death, highlighting a vulnerable developmental period for spinal cord oligodendrocytes.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Spinal cord injury can lead to cell death in oligodendrocytes, which are crucial for myelin formation.
- A specific developmental window exists for heightened oligodendrocyte vulnerability to apoptosis after injury.
- Caspases, a family of proteases, are implicated in programmed cell death.
Purpose of the Study:
- To investigate the role of caspases in oligodendrocyte apoptosis following spinal cord injury in a chick embryo model.
- To determine if caspase inhibitors can prevent or reduce injury-induced oligodendrocyte cell death.
- To characterize a specific developmental period of heightened caspase-dependent sensitivity in spinal oligodendrocytes.
Main Methods:
- Development of an embryonic chick spinal cord injury model.
- Analysis of apoptotic cell death in white matter regions caudal to the lesion.
- Immunostaining to identify oligodendrocytes and assess caspase activity (caspase-3-like and caspase-1-like).
- In vivo administration of specific caspase inhibitors.
Main Results:
- Developmental apoptosis in the cervical spinal cord white matter increased during the myelination period (embryonic days 13-18).
- Spinal cord transection induced a rapid increase in apoptotic cells, identified as oligodendrocytes, several millimeters caudal to the injury.
- Caspase-3-like activity, but not caspase-1-like activity, was involved in the apoptotic response.
- In vivo application of caspase inhibitors significantly reduced transection-induced oligodendrocyte apoptosis.
Conclusions:
- Oligodendrocytes in the embryonic chick spinal cord exhibit a caspase-dependent vulnerability to apoptosis after injury during a specific developmental period.
- Caspase inhibition is a potential therapeutic strategy to mitigate oligodendrocyte loss following spinal cord injury.