The Effects Of Proteo-β-glucan From Maitake On APP/PS1 Transgenic Mice Learning And Memory And The Molecular Mechanisms

Background: Alzheimer’s disease(AD)is one of the most important neurodegenerative diseases among the elderly.However,there is still a lack of effective drugs for the treatment of AD.It is urgent to discover effective anti-AD drugs.In the early stage,the team found that the active ingredient,Proteo-β-glucan from Maitake(PGM),from the wild fungus Grifola frondosa,can effectively combat Al Cl3-induced learning and memory impairment.And this effect is related to molecules regulating learning and memory.At present,many studies have shown that PGM can effectively regulate immune function and promote the function of related immune cells and inflammatory factors,and the relationship between neuroimmunity and AD has become a research hotspot.However,it is still unclear whether PGM can improve the learning and memory impairment of AD mice by regulating neuroimmune pathways.Based on this,this study intends to use amyloid precursor protein /presenilin-1(APP/PS1)double transgenic AD model mice to study the effect of PGM on learning and memory impairment and the molecular mechanism of participation;to study the effect of PGM on the characteristic pathological marker β amyloid protein(Aβ)of AD mice,and its effect on hippocampal neurons.The role of PGM in regulating the immune status of microglia,which are the main immune cells in the brain of AD mice,and its relationship with Aβ expression were explored.Furthermore,we elaborated the regulation of PGM on the expression of major inflammatory signaling pathways and inflammatory molecules.The research will provide new evidence for AD drug mining and for AD neuroimmunotherapy.Methods: 6-month-old C57BL/6J APP/PS1 double-transgenic mice and 6-month-old wild C57BL/6J mice in the same litter were grouped as the experimental subjects.PGM 5,10,20 mg/kg dose groups were generated and drugs were injected intraperitoneally.After 3 months,water maze positioning navigation and space exploration experiments were carried out to evaluate the effect of PGM on learning and memory behavior of mice.Then,H&E staining(Hematoxylin-eosin staining,H&E),Nissl staining(NS),immunohistochemistry and immunofluorescence were used to study the effect of PGM on Aβ and the relationship between immunomodulatory effects on microglia and Aβ changes.Finally,Western blot analysis was used to detect the downstream of TLR4/ My D88/NF-κB signaling pathway and the expression of inflammatory protein molecules.Results: The results of this study indicated that PGM effectively improved the learning and memory impairment of APP/PS1 transgenic mice,reduced Aβ deposition in mouse hippocampus tissues,and activated microglial immune status,and enhanced its clearance and phagocytosis of Aβ.H&E and NS staining results suggested that PGM improved the hippocampal morphology of mice and reduced neuronal death.Western blot results showed that PGM effectively regulated the changes of TLR4/My D88/NF-κB signaling pathway in hippocampus;and reduced the expression of proinflammatory state(M1)marker molecules IL-6,IL-1β,TNFα,and enhanced the status of anti-inflammatory factors(M2)and the expression of marker molecules IL-4,IL-10 and BDNF.However,the effect of PGM on the above results at low and high doses is not significant.Conclusion: PGM can effectively counteract learning and memory impairment in APP/PS1 mice,which may be related to its modulatory effect on neuroimmune pathways.