Protective effects of T-588, a novel cognition enhancer, on β-amyloid protein, serum deprivation and glutamate induced neurotoxicity in primary rat hippocampal neurons and cerebellar granule cells

• Published in: Japanese Journal of Pharmacology Vol. 73; no. suppl.2; p. 280
• Main Authors: Noboru Iwakami, Hidetoshi Yamaguchi, Satoshi Ono, Hirokazu Narita
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1997
• ISSN: 0021-5198; 1347-3506

Previously, we have demonstrated that T-588 exhibited protective effects against cerebral anoxia in mice, and ameliorated the memory and learning impairment in embolized and ischemic rats. In the present study, we investigated the protective effects of T-588 on in vitro models of neuronal cell death. Deposition of the β-amyloid protein (Aβ) is a characteristic of patients with Alzheimers disease (AD). Using primary rat hippocampal neurons and cerebellar granule cells, we examined the protective effects of T-588 against neuronal degeneration caused by Aβ(25-35). The cell viability was quantitated by the LDH method. T-588 (1-10 μM) significantly protected neurons against Aβ(25-35) induced neurotoxicity. Apoptosis can also induced in rat hippocampal neurons by deprivation of serum in culture media. T-588 (1-100 μM) prevented serum deprivation induced cell death in a concentration dependent manner. Rat hippocampal neurons and cerebellar granule cells undergo necrosis when they are exposed to glutamate (50 μM, 15 min). T-588 (100 μM) markedly reduced the neuronal cell death. These results suggest that T-588 can interrupt the neurodegeneration associated with AD.