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Differential effects of growth factors in bulbospinal neuron survival and neurite outgrowth in vitro Pataky, David Michael
Abstract
During development, the central nervous system (CNS) is capable of not only growth, but regeneration as well. There are two possible reasons why this ability is lost with maturation: 1) the CNS environment no longer supports growth, and 2) the capacity of the neurons for growth diminishes. There is good evidence that treating injured neurons with the appropriate small polypeptide growth factors can reverse their diminished growth capacity and overcome the inhibition of the mature CNS environment. Neurons in the brainstem with axonal projections to the spinal cord (bulbospinal neurons) are necessary for the initiation and control of many motor behaviours, notably locomotion. After spinal cord injury, these motor behaviours are permanently compromised due to the ineffectiveness of CNS repair. I hypothesized that treating bulbospinal neurons with the appropriate trophic factor(s) will enhance their growth. To address this hypothesis, I designed a novel assay to examine trophic effects on bulbospinal neurons specifically. The assay is based on retrogradely labeling the bulbospinal neurons as they develop axonal projections to the spinal cord in the chick embryo. Subsequently, the brainstem tissue is dissociated (whole or vestibulospinal) or explanted (vestibulospinal or reticulospinal) into culture, creating survival or neurite outgrowth assays respectively. Two families of growth factors, neurotrophins and Fibroblast Growth Factors (FGFs) were examined for trophic effects on bulbospinal neurons. The neurotrophins were largely ineffective, but NT-3 significantly increased neurite outgrowth from reticulospinal (not vestibulospinal) explants. Four FGFs (FGF-1, FGF-2, FGF-5 and FGF-9) were also tested. FGF-2 was the most effective, stimulating survival and neurite outgrowth for all populations examined. FGF-1 only enhanced bulbospinal neurite outgrowth, FGF-9 only survival, and FGF-5 was largely ineffective. At this stage of development, bulbospinal neurons did not express FGF receptors, but non-neuronal cells in situ and in vitro did. Astrocyte-conditioned medium also increased bulbospinal neuron survival, suggesting that perhaps the FGFs act by stimulating the production of the appropriate growth factor from non-neuronal cells. In conclusion, indirect effects may be an important mechanism for growth factor action on bulbospinal neurons. Furthermore, NT-3, FGF-1 and FGF-2 are good candidates for promoting regeneration from injured bulbospinal neurons in vivo.
Item Metadata
Title |
Differential effects of growth factors in bulbospinal neuron survival and neurite outgrowth in vitro
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2000
|
Description |
During development, the central nervous system (CNS) is capable of not only
growth, but regeneration as well. There are two possible reasons why this ability is lost
with maturation: 1) the CNS environment no longer supports growth, and 2) the capacity
of the neurons for growth diminishes. There is good evidence that treating injured
neurons with the appropriate small polypeptide growth factors can reverse their
diminished growth capacity and overcome the inhibition of the mature CNS environment.
Neurons in the brainstem with axonal projections to the spinal cord (bulbospinal
neurons) are necessary for the initiation and control of many motor behaviours, notably
locomotion. After spinal cord injury, these motor behaviours are permanently
compromised due to the ineffectiveness of CNS repair. I hypothesized that treating
bulbospinal neurons with the appropriate trophic factor(s) will enhance their growth.
To address this hypothesis, I designed a novel assay to examine trophic effects on
bulbospinal neurons specifically. The assay is based on retrogradely labeling the
bulbospinal neurons as they develop axonal projections to the spinal cord in the chick
embryo. Subsequently, the brainstem tissue is dissociated (whole or vestibulospinal) or
explanted (vestibulospinal or reticulospinal) into culture, creating survival or neurite
outgrowth assays respectively.
Two families of growth factors, neurotrophins and Fibroblast Growth Factors
(FGFs) were examined for trophic effects on bulbospinal neurons. The neurotrophins
were largely ineffective, but NT-3 significantly increased neurite outgrowth from
reticulospinal (not vestibulospinal) explants. Four FGFs (FGF-1, FGF-2, FGF-5 and
FGF-9) were also tested. FGF-2 was the most effective, stimulating survival and neurite
outgrowth for all populations examined. FGF-1 only enhanced bulbospinal neurite
outgrowth, FGF-9 only survival, and FGF-5 was largely ineffective. At this stage of
development, bulbospinal neurons did not express FGF receptors, but non-neuronal cells
in situ and in vitro did. Astrocyte-conditioned medium also increased bulbospinal neuron
survival, suggesting that perhaps the FGFs act by stimulating the production of the
appropriate growth factor from non-neuronal cells. In conclusion, indirect effects may be
an important mechanism for growth factor action on bulbospinal neurons. Furthermore,
NT-3, FGF-1 and FGF-2 are good candidates for promoting regeneration from injured
bulbospinal neurons in vivo.
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Extent |
7255475 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-07-15
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0089644
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2000-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.