Abstract:

Alzheimer’s disease is a common neurodegenerative disease. Microglia induces oxidative stress in the brain for engulfing bacteria and viruses. The accumulating data indicate that oxidative stress and apoptosis are two main actors for the induction of microglia activation-induced Alzheimer’s Disease. Oxidative stress is one of many triggers that activate the transient receptor potential melastatin 2 (TRPM2) channel. Glutathione (GSH) is a main cytosolic antioxidant in the mammalian cells. The GSH depletion via the activation of TRPM2 induces oxidative stress and apoptosis in neuronal cells. It has not yet been researched how GSH depletion via activation of TRPM2 affects oxidative stress and apoptosis in microglial cells with the Alzheimer's disease model. The BV2 cells divided into 5 groups as control, buthionine sulphoximine (BSO and 0.5 mM for 6 h), amyloid beta (1 uM for 72 h), amyloid beta+BSO, and amyloid beta+BSO+GSH (10 mM for 2 h). In the BSO group, the levels of apoptosis, mitochondrial membrane potential, cytosolic free oxygen reactive species (cyROS), caspase (Casps) -3, Casps -8, and Casps -9 were increased as compared to the control group, although cell viability level was decreased. The expression levels of TRPM2, Casps -3, Casps -9, Bax, Bcl-2, and PARP-1 were also increased in the BSO group. In addition, their levels were further increased in the amyloid beta and BSO+amyloid beta groups as compared to the BSO group. However, the changes were modulated in the BSO+amyloid beta+GSH group by the incubation of GSH. In conclusion, the depletion of GSH increased apoptosis and cyROS levels via activation of caspases and TRPM2 in the amyloid beta-induced microglia cells. The treatment of GSH may be a potential target on the apoptosis and oxidative stress in the amyloid beta-induced microglia cells.

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