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Title: Regulation of programmed cell death in the developing thalamus
Author: Asavaritikrai, Pundit
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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In this thesis, I examined PCD in the thalamus during the period of innervation of the cortex (late embryonic to early postnatal ages in mice). I found that apoptosis (revealed by TUNEL and pyknotic morphology) is a common mode of thalamic PCD both in vivo and in vitro. In vivo studies showed the highest rate of cell death is in early postnatal life, at postnatal day 1 (P1). In vivo analysis of animals lacking functional neurotrophin tyrosine kinase receptors, TrkB and TrkC, and in vitro work in collaboration with Dr Beau Lotto showed that brain-derived neurotrophic factor (BDNF), acting via TrkB, regulates thalamic survival in the perinatal period. My in vitro studies showed that thalamic cells cultured from E15 for up to 5 days showed a loss of viability after 2-3 days, which precedes the in vivo increase in thalamic PCD. Cortical factors in addition to BDNF are able to maintain thalamic viability for longer periods in culture. Later studies showed that these factors are not unique to the cerebral cortex but can be found in other neuronal tissues. Amongst other tissues, the late-gestation thalamus is able to produce them provided it is stimulated with elevated levels of K+. Elevated K+ is known to promote thalamic survival by increasing depolarisation but I found evidence that elevated K+ did not require TrkB or TrkC signaling to produce a trophic effect since K+ had normal trophic effects on the thalamic explants of either trkB (-/-) or trkC (-/-) animals. Moreover, I observed an increased cell death in the E19 thalamus in mice homozygous for a mutation of the transcription factor pax-6. This mutant is known to lack thalamocortical innervation and my in vivo and in vitro analysis of this mutant, suggested that thalamocortical innervation is essential for developing thalamic cells to obtain sufficient trophic factors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available