Biogenic Selenium Nanoparticles Attenuate Aβ25-35-Induced Toxicity in PC12 Cells via Akt/CREB/BDNF Signaling Pathway

Deposition of aggregated amyloid beta (Aβ) protein is considered to be a major causative factor that is associated with the development of oxidative stress and neuroinflammation in the pathogenesis of Alzheimer's disease (AD). Selenium nanoparticles (SeNPs) have been experimentally using for treatment of Neurological Disease due to their low toxicity, high bioavailability, and multiple bioactivities. This study was conducted to investigate the protective effects of biogenic SeNPs by Lactobacillus casei ATCC 393 against Aβ_25-35-induced toxicity in PC12 cells and its association with oxidative stress and inflammation. The results showed that SeNPs had no cytotoxicity on PC12 cells. Moreover, SeNPs entered cells through cellular endocytosis, which effectively attenuated Aβ_25-35-induced toxicity in PC12 cells. In addition, compared with Aβ_25-35 model group, SeNP pretreatment significantly enhanced the antioxidant capacity, inhibited the overproduction of Reactive Oxygen Species (ROS), effectively regulated the inflammatory response, decreased the activity of acetylcholinesterase, significantly reduced the expression level of Caspase-1 and the ratio of Bcl-2/Bax, and upregulated the expression level of p53. Furthermore, compared with Aβ_25-35 model group, SeNPs effectively promoted the phosphorylation of Akt and cAMP-response element-binding protein (CREB), and upregulated the expression level of brain-derived neurotrophic factor (BDNF). In addition, the Akt Inhibitor (Akt Inhibitor VIII, AKTi-1/2) could reverse the protective effects of SeNPs on PC12 cells. The Akt Agonist (SC79) had a similar effect on PC12 cells as that of SeNPs. Overall, this study demonstrated that biogenic SeNPs can effectively alleviate the Aβ_25-35-induced toxicity in PC12 cells via Akt/CREB/BDNF signaling pathway.

Alzheimer’s disease; BDNF; Biogenic selenium nanoparticles; CREB; Toxicity.