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Alzheimer's disease (AD) is characterized by the increase of hippocampal Ca2+ influx-induced apoptosis and mitochondrial oxidative stress (OS). The OS is a stimulator of TRPM2, although N-(p-amylcinnamoyl)anthranilic acid (ACA), 2-aminoethyl diphenylborinate (2/APB), and glutathione (GSH) are non-specific antagonists of TRPM2. In the present study, we investigated the protective roles of GSH and TRPM2 antagonist treatments on the amyloid beta 42 peptide (A beta)-caused oxidative neurotoxicity and apoptosis in the hippocampus of mice with AD model. After the isolation of hippocampal neurons from the newborn mice, they were divided into five incubation groups as follows: control, ACA, A beta, A beta+ACA, and A beta+GSH. The levels of apoptosis, hippocampus death, cytosolic ROS, cytosolic Zn2+, mitochondrial ROS, caspase-3, caspase-9, lipid peroxidation, and cytosolic Ca2+ were increased in the primary hippocampus cultures by treatments of A beta, although their levels were decreased in the neurons by the treatments of GSH, PARP-1 inhibitors (PJ34 and DPQ), and TRPM2 blockers (ACA and 2/APB). The A beta-induced decreases of cell viability, cytosolic GSH, reduced GSH, and GSH peroxidase levels were also increased in the groups of A beta+ACA and A beta+GSH by the treatments of ACA and GSH. However, the A beta-caused changes were not observed in the hippocampus of TRPM2-knockout mice. In conclusion, the present data demonstrate that maintaining the activation of TRPM2 is not only important for the quenching OS and neurotoxicity in the hippocampal neurons of mice with experimental AD but also equally critical to the modulation of A beta-induced apoptosis. |
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