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Title: ATP elicits electrophysiological and migratory responses in cells of the spinal cord stem cell niche
Author: MacLean, Claudia Catherine
ISNI:       0000 0004 6062 3349
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2016
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There are multiple similarities between the central canal region of the spinal cord and the adult neurogenic niches in the mammalian brain. The central canal region displays increased proliferation after injury with migration of the newly-proliferated cells to the site of injury and differentiation into astrocytes and oligodendrocytes. This study will look at the role of purinergic signalling in the ependymal cells and CSF-contacting cells (CSFcCs) as the CSFcCs present in this area express P2X receptors containing the P2X2 subunit. Local application of ATP elicited fast depolarisations via activation of suramin-sensitive channels in a subgroup of CSFcCs comprising both spiking and non-spiking subtypes of CSFcC (types 1, 2 and 3). The P2X2/3,3-specific antagonist A-317491 had no effect in the majority of CSFcCs but produced a reduction in depolarisation in a subgroup of CSFcCs predominantly located ventral to the central canal, with the ventral expression of the P2X3 subunit supported by immunohistochemistry. Ependymal cells and the remainder of CSFcCs produced a suramin-insensitive hyperpolarisation to the application of ATP or UTP, while producing a small depolarisation to the dinucleotide polyphosphate Ap4A. Modulation of purinergic signalling had no effect on proliferation rate in spinal cord slices over a 4 hour time period, nor did it affect the survival rate of the newly-proliferated cells over 5 days in organotypic slice cultures. In this model, inhibition of purinergic signalling with suramin reduced the migration of newly-proliferated ependymal cells away from the central canal, while inhibition of the breakdown of ATP by ARL 67156 facilitated this migration. The presence of fast acute responses to ATP including spatial variation in receptor subtypes indicates the importance of purinergic signalling in this area and the release of ATP known to be triggered by spinal cord injury could now have a role in the necessary migration of newly-proliferated ependymal cells.
Supervisor: Deuchars, Sue A. ; Deuchars, Jim ; Cohen, Netta Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available