Neurotoxicity induced by amyloid β-peptide and ibotenic acid in organotypic hippocampal cultures: protection by S-allyl- l-cysteine, a garlic compound

Abstract

We have assessed amyloid-β (Aβ)-induced neurotoxicity, with and without added ibotenic acid (IBO), a potent N-methyl- d-aspartate (NMDA) agonist, in an organotypic hippocampal slice culture (OHC). In the OHC, there was little neurotoxicity after treatment with Aβ 25–35 (25 or 50 μM) alone for 48 h. However, with IBO alone neuronal death was observed in the pyramidal cell layer at low concentrations, and there was dramatic neuronal death at concentrations of 65 μM or more. When Aβ was combined with IBO (Aβ+IBO) there was more intense cell death than with IBO alone. S-Allyl- l-cysteine (SAC), one of the organosulfur compounds having a thioallyl group in aged garlic extract, was shown to protect the hippocampal neurons in the CA3 area and the dentate gyrus (DG) from the cell death induced by Aβ+IBO with no change in the CA1 area. Although l-glutamate (500 μM) potentiated the degree of IBO-induced neuronal death, it attenuated the Aβ+IBO-induced neuronal death in both the CA3 area and the DG with no obvious effect on the CA1 area. These results suggest that Aβ+IBO induces extensive neuronal death, and that SAC and l-glutamate protect cells from death in specific areas of the hippocampus. In addition, inhibition using a pan-caspase inhibitor, z-VAD-fmk, only provided partial protection from Aβ+IBO-induced toxicity for the neurons in the CA3 area. These results suggest that multiple mechanisms may be involved in Aβ+IBO-induced neuronal death in the OHC.