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

Ito, Yoshihisa; Moriyuki, Itō; Takagi, Noritaka; Saito, Hiroshi; Ishige, Kumiko

doi:10.1016/s0006-8993(03)03173-1

Cited by 44 publications

(26 citation statements)

References 31 publications

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“…This is because several features of hippocampal circuitry are preserved, and the preparation is well suited for studies on prolonged pharmacological treatment and recovery, which would be difficult to perform in an intact animal experiment. We have reported that OHC cultured for 3 weeks showed little neurotoxicity after treatment with Aβ 1-40 or Aβ 25-35 (25 or 50 µM) alone for 48 h, whereas exposure of OHC to Aβ in combination with ibotenic acid, a potent N-methyl-Daspartate (NMDA) agonist, induced severe cell death when compared with the effect of ibotenic acid alone (15). This phenomenon was not observed in OHC cultured for 2 weeks or shorter periods.…”

Section: Introductionmentioning

confidence: 95%

“…The OHC was prepared as described previously (15). Under sterile conditions, the hippocampi were dissected out from anesthetized 6 -7-day-old Wistar / ST rats.…”

Section: Preparation Of Organotypic Hippocampal Slice Cultures (Ohcs)mentioning

confidence: 99%

“…The intensity of the fluorescence was quantitatively analyzed using Scion Image. The neuronal death in the selecting areas in the different cultures was expressed as relative percentage of the neuronal death in control OHCs (15).…”

Section: Drug Treatments and Assessment Of Neuronal Deathmentioning

confidence: 99%

“…A previous study from our laboratory has shown that when OHCs cultured for 3 weeks was treated with ibotenic acid, an NMDA agonist, at various concentra-tions for 48 h, the degree of PI fluorescence was clearly concentration-dependent within the range 5 -125 µM (15). Therefore, the degree of neuronal death induced by ibotenic acid was also compared among OHCs cultured for 3 -7 weeks.…”

Section: Aβ-and Ibotenic Acid-induced Toxicities In Ohcs Cultured Formentioning

confidence: 99%

“…In our studies, we have found that SAC protects against Aβ-induced cell death, but does not protect against 4-hydroxynonenalinduced cell death in either NGF-differentiated PC12 cells (22) or cultured hippocampal neurons (3). We have also reported that SAC protects hippocampal neurons in the CA3 area and the dentate gyrus (DG) from the cell death induced by Aβ in combination with ibotenic acid with no change in the CA1 area in OHC (15).…”

Section: Introductionmentioning

confidence: 96%

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Role of Caspase-12 in Amyloid β-Peptide-Induced Toxicity in Organotypic Hippocampal Slices Cultured for Long Periods

et al. 2007

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Abstract. Amyloid β (Aβ) toxicity has been implicated in cell death in the hippocampus, but its specific mechanisms are poorly understood. In this study, Aβ-induced cell death was investigated in organotypic hippocampal slice cultures (OHCs) that were cultured for various periods in vitro. There were no obvious histological differences among slices cultured for 3 to 7 weeks in vitro. Although there was little neurotoxicity after treatment with Aβ 25-35 in OHCs cultured for relatively shorter periods (3 -5 weeks), age-dependent cell death was evident in OHCs cultured for relatively longer periods (6 -7 weeks) after exposure to Aβ 25-35 . In OHCs cultured for 7 weeks, S-allyl-L-cysteine (SAC), a component of aged garlic extract, protected the cells in areas CA1 and CA3 and the dentate gyrus from Aβ 25-35 -induced toxicity. The immunoreactivity of cleaved caspase-12 was increased whereas that of glucose-regulated protein 78 was not altered after exposure to Aβ [25][26][27][28][29][30][31][32][33][34][35] . The increases in the cleaved caspase-12 were also reversed by simultaneously applied SAC. These results suggest that OHCs cultured for relatively longer periods are more susceptible to Aβ-induced toxicity and that the Aβ-induced cell death involves caspase-12-dependent pathways. It is also suggested that SAC is able to protect against the Aβ-induced neuronal cell death through the inhibition of the caspase-12-dependent pathway.

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Section: Introductionmentioning

confidence: 95%

“…The OHC was prepared as described previously (15). Under sterile conditions, the hippocampi were dissected out from anesthetized 6 -7-day-old Wistar / ST rats.…”

Section: Preparation Of Organotypic Hippocampal Slice Cultures (Ohcs)mentioning

confidence: 99%

Section: Drug Treatments and Assessment Of Neuronal Deathmentioning

confidence: 99%

Section: Aβ-and Ibotenic Acid-induced Toxicities In Ohcs Cultured Formentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 3 more Smart Citations