Hippocampal CA1 region neurodegeneration produced by ethanol withdrawal requires activation of intrinsic polysynaptic hippocampal pathways and function of N-methyl-D-aspartate receptors.

摘要: Abstract Long-term intake of ethanol produces adaptive alterations in multiple transmitter systems the hippocampal formation that likely contribute to withdrawal-induced seizure and excitotoxicity. The present studies were designed examine role N-methyl- d -aspartate receptor activation cytosolic Ca2+ accumulation neurotoxic effects withdrawal. Further, these investigated network excitation promoting both neurotoxicity during Chronic, continuous (11 day) exposure (91 mM starting concentration) did not produce any region organotypic explants, as measured by uptake non-vital fluorescent marker propidium iodide. Withdrawal from chronic (10 was associated with rapid (30 min) significant increases intracellular Ca2+, assessed visualization Calcium-Orange fluorescence, each explants. However, observed 24 h after initiation withdrawal only seen cornu ammonis 1 (CA1) region. Exposure MK-801 (20 μM) at start markedly attenuated entry all regions, well as, CA1 neurodegeneration. treatment explants tetrodotoxin (500 nM) surgical transection mossy fiber or Schaffer collateral projections immediately prior blocked regional neurotoxicity. These data suggest neurodegeneration is dependent upon polysynaptic propagation action potentials (“network excitation”) whole-hippocampal glutamatergic systems.