Role of caspase-12 in amyloid beta-peptide-induced toxicity in organotypic hippocampal slices cultured for long periods.

Contains fulltext : 53396.pdf (publisher's version ) (Open Access)Amyloid beta (Abeta) toxicity has been implicated in cell death in the hippocampus, but its specific mechanisms are poorly understood. In this study, Abeta-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 Abeta25-35 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 Abeta25-35. 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 Abeta25-35-induced toxicity. The immunoreactivity of cleaved caspase-12 was increased whereas that of glucose-regulated protein 78 was not altered after exposure to Abeta25-35. 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 Abeta-induced toxicity and that the Abeta-induced cell death involves caspase-12-dependent pathways. It is also suggested that SAC is able to protect against the Abeta-induced neuronal cell death through the inhibition of the caspase-12-dependent pathway

Biochemische und histochemische Untersuchungen zum Eiseninduzierten oxidativen Stress in vivo und zur Toxizitaet von Trichlormethylharmanderivaten an dopaminergen Primaerkulturen in vitro Abschlussbericht

Available from TIB Hannover: DtF QN1(78,36) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Neurotoxine und Neuroprotektion. Teilprojekt: Chloral-abgeleitete endogen auftretende Neurotoxine: Synthese, Analytik, in-vivo-Entstehung und moegliche Induktion neurodegenerativer Erkrankungen Abschlussbericht

Aim of the project was to elucidate the role of oxidative stress and of exogenous toxins in Parkinson's disease. It could be shown in pm-studies that GSH is reduced and that there is a further decline in the processing stages, while iron increases. An increase of 8-hydroxy-2-desoxyguanosin indicates that DNA undergoes oxidation. Intranigral/intrastriatal administration of iron in rats shows progressive loss of DA, DOPAC, HVA and loss of neutrons in the SN indicating iron-induced oxidative damage. In platelets of PC patients a deficit of coenzymen Q-10 shows disturbance of the electron-transport system at a time when respiratory chain enzymes and MAO-B are not changed. In analogy to MPTP/MPP"+ a cell destructing action of TaClo and N-CH_3-TaClo could be shown (TH-IR reduced in SN of rats, toxicity at the glial level, reduced DA- and GABA-uptake, release of LDH). TaClo and several of its analog compounds are protein blocker of the respiratory chain, especially of complex I. In vivo-studies in rats after chronic TaClo administration have demonstrated changes in respiratory chain enzymes which will be studied in detail in upcoming experimental trials. (orig.)SIGLEAvailable from TIB Hannover: F99B1369 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman