Thresholds exist in brain mitochondria whereby their respiratory chain complex activities need to be reduced by certain percentages before major changes in oxidative phosphorylation will occur. Synaptic mitochondria have lower complex thresholds than non-synaptic mitochondria, a finding which has important implications for neurodegeneration in general. This project will investigate mitochondrial respiratory chain complex thresholds in neuronal and astrocytic cell lines. The objectives are to: 1. Establish the techniques that have been learnt during the initial fellowship in the return-grant-laboratory.
2. Estimate the threshold levels that exist in neuronal and astrocytic cell lines.
3 Deplete cells of the antioxidant glutathione and to record any effects on the respiratory chain complex thresholds.
4. Use antioxidants (ascorbate, tocopherol, lazaroids) and growth factors (NGF, BDNF) in an attempt to increase threshold levels in neuronal and astrocytic cells, thus providing a possible means of neuroprotection and astroprotection.