Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598166
Title: Neurotrophic responses of developing Gonadotropin-releasing hormone neurons
Author: Cronin, A. S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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Abstract:
The studies described in this thesis investigated the hypothesis that the development of GnRH neurite outgrowth is promoted by BDNF. The objectives were to establish whether BDNF and its receptor TrkB were expressed in regions associated with developing GnRH neurons, and then to ascertain whether BDNF elicited neurotrophic effects in GnRH neurons. In situ hybridisation revealed that during development from E12.5 to adult, BDNF mRNA was found throughout the hypothalamus, from the POA to the medial basal hypothalamus. TrkB mRNA (which encodes the receptor for BDNF) was found in the region of the olfactory tracts and bulbs at E14.5-16.5, and throughout the brain from E16.5 to adulthood. Furthermore, the majority of cultured embryonic GnRH cells were immunoreactive for TrkB. These primary cell cultures were used to investigate the actions of BDNF on GnRH neurite outgrowth. Treatment with BDNF for 39 hours induced a significant increase in the length of neurites, but had no discernible affect on branching. Subsequent investigations into the signalling pathway by which BDNF may exert this response revealed induction of phospho-Ca2+/cAMP response element-binding protein (pCREB) in GnRH and non-GnRH cells following an acute BDNF treatment. BDNF is known to induce phosphorylation of CREB in other neuronal types via the Ras-microtubule associated protein kinase/extracellular-regulated kinase (Ras-MAPK/ERK) pathway which also results in neurite outgrowth, so the response to BDNF of ERK, an upstream MAP kinase of CREB, was also tested in GnRH cells. It was discovered that pCREB was induced in GnRH cells following treatment with BDNF, but this was not associated with induction of pERK, though BDNF treatment did stimulate pERK in neighbouring non-GnRH cells. In summary, GnRH cells possess the receptor for BDNF, TrkB, and that during their development, the neurites they elaborate course through BDNF-rich areas of the brain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.598166  DOI: Not available
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