The role of lactate in supporting neuronal survival and synaptic function after oxygen and glucose deprivation in the rat hippocampus

Cater, Heather Lucy (1999) The role of lactate in supporting neuronal survival and synaptic function after oxygen and glucose deprivation in the rat hippocampus. University of Southampton, Doctoral Thesis.

Abstract

We have studied the effects of lactate on neuronal survival in vitro after oxygen and glucose deprivation in organotypic hippocampal slice cultures. When cultures were exposed to ischaemic conditions (60 minutes combined oxygen and glucose deprivation), lactate (6mM and 30mM) significantly improved neuronal survival compared to no energy substrate although it was significantly less effective than glucose (30mM). Addition of the lactate uptake inhibitor, α-cyano-4-hydroxycinnamin (4CIN, 0.5mM) significantly increased neuronal damage when added during the oxygen/glucose deprivation period compared to no energy substrate.

We then tested the effects of hypoxia (60 minutes of oxygen deprivation in the presence of glucose) and found that 5 and 30mM lactate, when present throughout the insult and the post-insult period, significantly improved neuronal survival compared to no energy substrate. In fact 5mM lactate was as effective as glucose in supporting neuronal survival. Furthermore, 5mM lactate also improved neuronal survival when it was present only aft er the hypoxic insult. 2DG had no effect on the ability of 5mM lactate to improve neuronal survival after oxygen deprivation suggesting that lactate can be neuroprotective by directly entering into the TCA cycle.

We investigated the role of lactate during glucose deprivation in the presence of oxygen (hypoglycaemia) in hippocampal slice cultures.

We also studied the effects of lactate on synaptic function in CA1 pyramidal cells in acute hippocampal slices and organotypic hippocampal slices using field potential recordings.

Taken together with other reports in the literature, the results provide strong support for the existence of a lactate-shuttle between astrocytes and neurones. Lactate appears to be essential for the maintenance of neuronal survival and synaptic function in the absence of glucose and may improve neuronal survival and restoration of synaptic activity after oxygen deprivation.

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