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.

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 > School of Psychology & Neuroscience
• 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: https://theses.gla.ac.uk/id/eprint/4837