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Characterisation of cells in the postnatal neurogenic niche of the murine spinal cord

Corns, Laura Frances (2012) Characterisation of cells in the postnatal neurogenic niche of the murine spinal cord. PhD thesis, University of Leeds.

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Abstract

The area surrounding the central canal of the spinal cord is a highly plastic region containing a range of poorly defined cell types, including ependymal cells and cerebrospinal fluid-contacting cells (CSFcCs). This study aims to characterise ependymal cells and CSFcCs, determining whether they are capable of responding to neurotransmitters. To test the hypothesis, whole cell patch clamp electrophysiology and intracellular dye-loading in in-vitro Wistar rat and C57/bl6 mouse spinal cord slices were combined with immunohistochemistry. CSFcCs could be categorised into three subtypes based on their voltage responses to positive current pulses. CSFcCs did not show an immediate electrophysiological response to 5HT or substance P but could respond to GABA with a GABAA receptor mediated depolarisation or hyperpolarisation. Ependymal cells were defined by their passive response properties and high degree of gap junction coupling and could depolarise in response to GABA; this could only be partially antagonised by the GABAA antagonist, bicuculline. CSFcCs and ependymal cells were both depolarised by ACh, with the size of the cholinergic response increasing from ependymal cells and subtype 1 CSFcCs to subtype 3 CSFcCs. Evidence indicated that the response was direct and mediated by nicotinic ACh receptors (nAChRs). Antagonism by the non α7*nAChR antagonist dihydro-β-erythroidinne or potentiation by the α7*nAChR modulator PNU-120596 revealed that non α7*nAChRs predominantly mediate the cholinergic responses but there is also a contribution from α7*nAChRs. These contributions varied between ependymal cells and the different CSFcC subtypes, reflecting variation in the functional responses of these cells. GABA and ACh modulate neurogenesis and plasticity in other neurogenic niches and these results demonstrate that they are also capable of modulating cells within the neurogenic niche of the postnatal spinal cord. Manipulation of these neurotransmitter systems could influence ependymal cell proliferation and differentiation resulting in beneficial implications for the treatment of spinal cord pathologies.

Item Type: Thesis (PhD)
ISBN: 978-0-85731-307-2
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds)
Identification Number/EthosID: uk.bl.ethos.595056
Depositing User: Repository Administrator
Date Deposited: 10 Mar 2014 10:16
Last Modified: 03 Sep 2014 10:49
URI: http://etheses.whiterose.ac.uk/id/eprint/5431

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