Beneficial And Mechanistic Effects Of A Fibroin Enzymatic Hydrolysate On Memory Impairment Induced By Amyloid Beta In Mice

Alzheimer’s disease is characterized by the deposition of amyloid plaques and subsequent formation of neuro-fibrillary tangles in the brain. A lack of safe and effective treatments exists to slow progression and prevents neurodegenerative diseases. In this study, amyloid beta (AB)(2 μg/3 μL) was injected (intrahippocampal) into mice to induce memory loss to investigate the beneficial effects of a silk fibroin enzymatic hydrolysate (FEH) with an average molecular weight of 2700 Daltons on memory and learning impairment which were assessed using the Morris water maze, passive avoidance, and Y-maze tests. Protein expression of BDNF-associated and p75 apoptotic signaling pathways were determined to investigate mechanistic effects of FEH. Oral FEH supplementation (10 mg/kg) significantly ameliorated AB-induced memory and learning impairment with higher doses producing small, additional increases. FEH treatment increased the levels of brain-derived neurotrophic factor (BNDF) and reduced the levels of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6) in brain hippocampal tissues of AB-treated mice.FEH stimulated the BDNF/tropomyosin receptor kinase B/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/postsynaptic density protein 95 pathway and suppressed the expression of proteins of the p75 apoptotic signaling pathway, including tumor necrosis receptor-associated factor 6, B-cell lymphoma 2 (Bcl2)/Bcl2-associated X protein, caspase-3, and nuclear factor-kappa B (NF-κB) in the brain hippocampus of amyloid beta-administered mice. These results support previous human studies indicating the potential of FEH supplementation to prevent memory and learning impairment, and provide data concerning its underlying mechanism of action.