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Title: The mechanisms of hypoglycaemia-induced cell damage in the striatum
Author: McDermott, Caroline Julia
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2001
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Glucose deprivation involved in hypoglycaemia has been associated with neurotoxicity and cell death. It is hypothesised that this neurotoxic process is initiated by a fall in cellular ATP concentration and a dysfunction of the Na+/K+ ATPase pump. Consequently the plasma membrane depolarises, opening the VGCC and allowing an excessive influx of calcium, which initiates glutamate release, ROS generation and the opening of the MTP. This intracellular activity subsequently triggers the apoptotic machinery necessary to promote irreversible cell death. In this study, primary cultures of embryonic rat striatal neurones were exposed to hypoglycaemia for periods between 1 hour and three days. Mitochondrial respiratory function and cytoskeletal integrity were affected. However several observations were found that conflicted with the general consensus of the mechanisms involved in hypoglycaemia-induced cell death. Evidence was obtained that there was :- 1. No calcium influx upon hypoglycaemia, indicating that the cell membrane does not depolarise 2. No glutamate toxicity 3. No ROS toxicity 4. No MTP involvement 5. DNA fragmentation independent of caspase activity 6. Reversal of cell damage upon the replacement of glucose 7. A decrease in intracellular calcium concentration upon glucose replacement. These data suggest that the removal of glucose from striatal cultures does not cause cell death but triggers the cell to enter a quiescent state with sufficient energy to maintain resting membrane potential but also with morphological, mitochondrial and DNA modifications. In conclusion striatal cells possess a neuroprotective mechanism against prolonged glucose deprivation and remarkably can recover metabolically with repaired DNA.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology