Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.642210
Title: Expression of the sensory neuropeptide encoding genes, βPPT-A and α-CGRP in adjuvant-induced joint inflammation
Author: Bulling, Duncan George Spencer
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Abstract:
Following the observation that individuals with hemiplegia or poliomyelitis resist the development of rheumatoid arthritis in the affected limb the sensory nervous system has been implicated in the aetiology of joint inflammation. Sensory neuropeptides, produced in dorsal root ganglia (DRG), released from central and peripheral terminals of sensory nerves upon noxious stimulation, are implicated in central and peripheral events underlying inflammation. Previous work has explored neuropeptide gene expression in DRG neurones in the Freund's Complete Adjuvant (FCA) model of unilateral tibio-tarsal joint inflammation. Within 8h of FCA injection, expression of mRNAs from the β preprotachykinin-A (β PPT-A) gene, encoding the sensory neuropeptides substance P and neurokinin A, and the α-calcitonin gene-related peptide (CGRP) encoding gene increase in small diameter innervating DRG neurones. Small diameter sensory nerves include the class of nerve implicated in the transmission of noxious stimuli. No changes occur in contralateral DRG neurones. A recent report of mRNAs encoding various transcription factors in innervating over the first 8h after FCA injection members showed that AP-2 mRNA increased in small diameter neurones within 1h of adjuvant injection, returning to control levels at subsequent time points. Despite members of the AP-1 transcription factor group been implicated in the control of PPT -A in vitro mRNAs encoding members of AP-1 family were not detected or showed no changes in expression. The same was found for NGF1-A and NGFI-B. The aim of this thesis was to utilise in-situ hybridisation to explore the early changes in βPPT-A and α-CGRP mRNAs, and the possible role of AP-2 in their regulation over the first 8h after FCA injection. Subsequent investigations were designed to investigate molecular mechanisms underlying changes in neuropeptide gene expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.642210  DOI: Not available
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