Wasp Venom Relieves Alzheimer's Phenotypes in 5xFAD Transgenic Mice through Inhibition of Aβ Aggregation

Abstract

Alzheimer’s disease (AD), a neurodegenerative disorder, has been known to be mostly commonly diagnosed in people over the age of 65. However, there is no drug that can cure AD. This study aimed to investigate if wasp venom (WV) can mitigate phenotypes of AD using a 5xFAD transgenic mouse model. The mice were administered intraperitoneally with WV obtained from Vespa velutina at a concentration of 250 or 400 μg/kg body weight (BW) once a week for a total of 14 weeks. WV treatment was shown to alleviate memory impairments in 5xFAD mice in behavioral tasks, including passive avoidance, Y‐maze and Morris water maze tests. In addition, we found that WV treatment decreased the level of 8‐hydroxy‐2′‐deoxyguanosine, a biomarker of oxidative DNA damage, in mouse plasma and the level of malondialdehyde, an indicative of lipid peroxidation, in liver and cerebral cortex, indicating that WV prevents oxidative damage. In particular, WV treatment increased expression of antioxidant‐associated proteins, a nuclear factor erythroid‐derived 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1), in the cerebral cortex and decreased inflammation‐associated protein, cyclooxygenase‐2 (COX‐2), amyloid beta (Aβ) plaque‐associated proteins, C‐terminal fragment (C99), and beta‐site amyloid precursor protein cleaving enzyme 1 (BACE1, β‐secretase) in the hippocampal tissue homogenates. Furthermore, we confirmed that WV treatment reduced the accumulation of Aβ plaque in the hippocampal area via thioflavin S staining. Taken together, these findings suggest that WV could ameliorate AD symptoms and delay AD onset and progression.