Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559481
Title: Characterisation of a human microglial cell line and study of interaction between microglia neurons in the rat hippocampus
Author: Nicholson, Elizabeth
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2009
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Abstract:
Microglia are the resident immunocompetent cells of the central nervous system (CNS). In response to insult or injury, microglia become more amoeboid, migrate to the site of injury, proliferate, phagocytose pathological stimuli and release growth factors and cytokines, thus initiating the inflammatory response. Due to these immune functions, much research has been invested in characterising their membrane physiology to investigate potential therapeutic targets. Despite being a non-excitable cell, microglia express an array of ion channels, which shape their physiological functions. One aim of this project was to characterise the ion channels functionally present in the human microglial cell line, C13-NJ, through cell attached and whole-cell voltage-clamp techniques. These experiments revealed that C 13-NJ cells express functional Na + and large conductance Ca2+ activated K+ channels, a well as a channel mediating a TRPM7 -like current. Further to the characterisation of ion channels, Gq-protein-coupled receptor related Ca2+ signalling was investigated using standard Ca2+ imaging techniques. Numerous GPCRs were identified and mechanisms of Ca2+- mobilisation and influx were determined. The functional consequences of histamine receptor 1 activation were also fully investigated, which was found to be pro-inflammatory due to the resultant increased migration, proliferation and cytokine release upon application of histamine. In addition to the well established role microglia have in the inflammatory response, recent research has revealed a role for microglia in non-pathological neuronal and synaptic function. Chemokines tethered to neuronal membrane, such as fractalkine and CD200 bind to receptors that are primarily expressed on ~ cells of myeloid lineage (such as microglia) and are prime candidates for a mechanism of this interaction. Extracellular field recordings and a range of intracellular recording techniques in acute rat hippocampal brain slices demonstrated that exogenous application of fractalkine or CD200 evokes depression of basal synaptic transmission. Mechanisms of these actions were further elucidated and discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.559481  DOI: Not available
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