Beneficial effect of BDNF via TRPM2 channel inhibition on oxidative stress and apoptosis increases in neuronal cell lines induced by experimental Alzheimer's disease

ABSTRACT Beneficial Effect of BDNF via TRPM2 Channel Inhibition on Oxidative Stress and Apoptosis Increases in Neuronal Cell Lines Induced by Experimental Alzheimer's Disease Alzheimer's disease (AlzH) is a progressive neurodegenerative disorder with symptoms such as memory loss, weakening of cognitive functions, and behavioral changes, affecting especially the elderly population, which is the most common cause of dementia. The etiology of the disease is unknown, but it involves the production of highly reactive oxygen species (ROS) caused by amyloid beta (Aβ) accumulation and Ca+2 influx. The SH-SY5Y cells are widely used in the experimental Aβ -induced AlzH model as a neural cell model that naturally contains the TRPM2 cation channel structure. Brain-derived neurotropic factor (BDNF) is made by brain cells and is important for keeping neurons healthy. It also has antioxidant and Ca+2 channel-regulating effects. But the effect of BDNF therapy on oxidative stress and apoptotic values caused by TRPM2 stimulation in neuronal cells activated with Aβ has not yet been studied. In SH-SY5Y cells, the effect of BDNF therapy on cell death, oxidative stress, and apoptosis values caused by the TRPM2 channel activated by Aβ was studied using molecular techniques. The SH-SY5Y cells were divided into five groups, including control, BDNF, Aβ, Aβ + BDNF, and Aβ + TRPM2 channel blockers (ACA and 2APB). The cells were analyzed with a laser confocal microscope, a Western blot, and a plate reader. Compared to control and BDNF groups, Aβ-stimulated cells showed increases in intra-cellular Ca+2 levels, ROS, mitochondrial membrane depolarization, cell death (PI-positive cell count), apoptosis, caspase activities (caspase-3, -8 and -9), TRPM2, PARP1, caspase-3, and caspase-9 expression levels. However, after BDNF therapy (in the Aβ + BDNF group), increased apoptosis, cell death, caspase and reduced oxidative values were observed. As a result, TRPM2 channel activity was demonstrated in neuronal cells on the parameters of Aβ-induced Ca2+ influx, oxidative stress, cell death, and apoptosis. TRPM2 channel inhibition with BDNF therapy appears to be a potential source for preventing Aβ-induced oxidative stress, apoptosis, and cell death. Keywords: Apoptosis, Alzheimer's disease, BDNF, Oxidative stress, Neuroplasticity, TRPM2 channel.