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 (MbetaCD). Results obtained demonstrate that MbetaCD 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 MbetaCD in preventing the pathological changes in synaptic activity induced by ischemia and indicate that manipulation of lipid components of membrane rafts might provide a new approach for the treatment of ischemia.
Rufini
Stefano
S
Department of Biology, Università degli Studi di Roma Tor Vergata, Rome, Italy. rufini@uniroma2.it
Grossi
Daniele
D
Luly
Paolo
P
Tancredi
Virginia
V
Frank
Claudio
C
D'Arcangelo
Giovanna
G
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology*; D002784:Cholesterol / Q000172:deficiency*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000503:physiopathology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000494:pharmacology
D047392:beta-Cyclodextrins; D016202:N-Methylaspartate; D002784:Cholesterol; D005947:Glucose; D007608:Kainic Acid