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Title: Neurotrophic factor regulation of gene expression in primary sensory neurons of the mouse
Author: Lawler, Polly Anne
ISNI:       0000 0004 2751 0932
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2007
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In this study, the expression of several sensory neuron specific/predominant genes, and the effects of neurotrophic factors upon them were studied in embryonic, postnatal and adult mouse sensory neurons. In the embryonic mouse, NGF/TrkA signalling was shown to be essential for the expression of mRNAs encoding substance P and the sodium channels Navl.8 and Navl.9 in DRG and trigeminal ganglia. Differential regulation of the two isoforms of calcitonin gene related peptide (CGRP) mRNA was apparent in the DRG with a requirement of NGF/TrkA signalling for expression of a, but not p CGRP. This was not reflected in the trigeminal ganglia. Postnatally, experiments revealed that NGF/TrkA signalling within the DRG and trigeminal ganglia is 1) essential for expression of SP, ocCGRP, pCGRP, Navl.8, Navl.9 mRNAs, 2) possibly required for expression of the neuropeptide galanin and the capsaicin receptor vanilloid receptor 1 (VR1) mRNAs, 3) not required for pituitary adenylate cyclase-activating peptide (PACAP) mRNA. Conversely, within the nodose ganglia, expression of Navl .8 and Navl .9 mRNAs did not require NGF/TrkA signalling. No regulation of all aforementioned genes by neurotrophin-3 (NT-3) was observed in trigeminal, nodose or dorsal root ganglia. In the adult mouse, DRG cultures were utilised to study gene regulation by the neurotrophic factors NGF, artemin and macrophage stimulating protein (MSP). Expression of SP, aCGRP, pCGRP, Navl.8, Navl.9 and VR1 mRNAs all showed a decrease following 96 hours in culture that was inhibited by presence of MSP (50ng/ml), NGF (lOng/ml) or artemin (lOng/ml). PACAP, galanin, damage induced neuronal endopeptidase (DINE) and activating transcription factor 3 (ATF3) mRNAs increased over time, but neurotrophic factors could impede such increases. No axotomy or neurotrophic factor-induced effects were observed for P2X3, Navl.6 or Navl.7 mRNAs. Interestingly the additional presence of leukaemia inhibitory factor (LIF) opposed NGF, MSP and artemin-induced effects on PCGRP, SP, VR1 and galanin mRNAs, whilst enhancing effects on PACAP and DINE transcripts.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available