Abstract: Objective To investigate the effects of sesamin on learning,memory and neuroinflammation in Alzheimer's disease(AD)rats based on RIP1/RIP3/MLKL pathway.Methods AD rats models were established by injecting amyloid beta 1-42(Aβ1-42)solution.The rats were randomly divided into AD group,low-dose sesamin(sesamin-low,80 mg/kg)group,high-dose sesamin(sesamin-high,160 mg/kg)group,piracetam(500 mg/kg)group,and sesamin-high+rRIP1(8 μg/kg)group.Ten rats injected with normal saline served as the blank group.After intervention,behavioral tests were conducted to evaluate spatial learning and memory abilities in the rats.ELISA was used to detect the levels of Aβ1-42,interleukin(IL)-1β,tumor necrosis factor(TNF)-α,and IL-6.Tissue sections were prepared to examine pathological morphology,neuronal apoptosis,and glial fibrillary acidic protein(GFAP)expression.Western blot was performed to detect the expression of proteins realted to the RIP1/RIP3/MLKL pathway.Results Compared with blank group,AD group showed increased escape latency,elevated levels of Aβ1-42,IL-1β,TNF-α,and IL-6,increased neuronal apoptosis,enhanced GFAP expression,and upregulated expression of RIP1,RIP3,and MLKL,along with reduced platform crossing frequency(all P<0.05).Compared with AD group,sesamin-low group,sesamin-high group,and piracetam group exhibited decreased escape latency,reduced levels of Aβ1-42,IL-1β,TNF-α,and IL-6,decreased neuronal apoptosis,diminished GFAP expression,downregulated expression of RIP1,RIP3,and MLKL,and increased platform crossing frequency(all P<0.05).Compared with sesamin-high group,sesamin-high+rRIP1 group shouwed increased escape latency,elevated levels of Aβ1-42,IL-1β,TNF-α,and IL-6,increased neuronal apoptosis,enhanced GFAP expression,upregulated expression of RIP1,RIP3,and MLKL,and reduced platform crossing frequency(all P<0.05).Conclusion Sesamin alleviates neuroinflammation and improves learning and memory abilities in AD rats by inhibiting the RIP1/RIP3/MLKL pathway.

Key words: Alzheimer's disease, learning and memory abilities, neuroinflammation, sesamin, RIP1/RIP3/MLKL pathway