The mechanisms of hypoglycaemia-induced cell damage in the striatum

McDermott, Caroline Julia (2001) The mechanisms of hypoglycaemia-induced cell damage in the striatum. PhD thesis, University of Glasgow.

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Abstract

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.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QH Natural history > QH301 Biology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Funder's Name: UNSPECIFIED
Supervisor's Name: Morris, Professor Brian
Date of Award: 2001
Depositing User: Ms Mary Anne Meyering
Unique ID: glathesis:2001-4837
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 16 Jan 2014 09:57
Last Modified: 24 Jan 2014 16:31
URI: http://theses.gla.ac.uk/id/eprint/4837

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