Cholesterol depletion inhibits electrophysiological changes induced by anoxia in CA1 region of rat hippocampal slices

The hyper-activation of glutamate receptors is a key event in the degenerative processes triggered by ischemia in the brain. Several types of these receptors reside in cholesterol-sphingomyelin rich domains of post synaptic plasma membranes and have been described to be sensitive to cholesterol depletion. Hence we investigated, by extracellular recordings, the effect of cholesterol depletion on population spikes (PS) during ischemia-like conditions in the CA1 region of rat hippocampal slices using the cholesterol-depleting agent methyl-beta-cyclodextrin (MβCD). Results obtained demonstrate that MβCD prevents the changes induced by anoxic insult: i.e. depression of the population spike amplitude and insurgence of ischemic long-term potentiation. Furthermore cholesterol depletion prevents the disappearance of population spike induced by anoxia/aglycemia during kainate perfusion. Our data suggest a possible role of MβCD in preventing the pathological changes in synaptic activity induced by ischemia and indicate that manipulation of lipids components of membrane rafts might provide a new approach for the treatment of ischemia.