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Title: Characterising properties and responses of cells in the postnatal neurogenic niche of the spinal cord
Author: Daniel, Jillian Marcia
ISNI:       0000 0004 5994 9552
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2015
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The area of the spinal cord surrounding the central canal may have postnatal neurogenic potential since under certain conditions, proliferation and differentiation of cells may occur. This region consists mainly of ependymal cells interspersed with a population of cells known as cerebrospinal fluid contacting cells (CSFcCs). This study examined properties and proliferation potential of these 2 cell types. Using a number of markers for CSFcCs, these were found to be present throughout the spinal cord, the greatest numbers in the thoracic area. Examination of the numbers of CSFcCs at different ages revealed a decrease over the first 2 months, but with no further decline up to 6 months. Ependymal cells surrounding the central canal can proliferate and differentiate. The specific environmental conditions, including modulation by neurotransmitters which could influence the ability of these cells to proliferate and differentiate have rarely been investigated. Both ependymal and CSFcCs can respond to acetylcholine (ACh); mediated in part by the alpha7 containing nicotinic ACh receptor (alpha7nAChR). Since ACh can promote proliferation and differentiation of cells in other CNS neurogenic niches, its effect on spinal cord cells in the central canal region was tested. Using EdU, a nucleoside analogue of thymidine to label proliferating cells, ACh was found to promote the proliferation of ependymal cells in mice under both in vitro and in vivo conditions. Application of the a7nAChR modulator PNU-120596 in spinal cord cultures and in vivo induced proliferation, producing ependymal cells expressing the stem cell marker Sox- 2. The proportion of EdU labelled cells that expressed the oligodendrocyte marker PanQKI was also increased, indicating that differentiation of cells down an oligodendrocyte lineage was promoted. The alpha7nAChR antagonist Methyllycaconitine reduced the PNU-120596 and ACh mediated proliferation. This opens new possibilities for treatment following spinal injury or demyelinating diseases such as multiple sclerosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available