To Explore The Effects Of BMP4 On Alzheimer’s Disease Based On Transgenic Animal Models And Nerve Cells

Background: Alzheimer’s disease(Alzheimer’s disease,AD)is a neurodegenerative and worldwide epidemic disease with hidden onset and a chronic progressive exacerbation of the disease,which mainly harms the elderly over 65 years old.AD pathogenesis is very complex and greatly hinders clinical treatment,so the cost of clinical treatment is extremely high,which brings heavy economic burden to global medical treatment.A new study has found that bone morphogenetic proteins(Bone morphogenetic proteins,BMPs)are involved in the regulation of the hippocampus nerve in brain tissue stem cell generation,inhibit the proliferation of hippocampal neurons and participate in the development of AD.Purposes:(1)To Explore whether BMP4 overexpression is a risk factor for Alzheimer’s disease;(2)Exploring the Pathological Mechanism of bmp4 in Alzheimer’s Disease.Methods:We used transgenic mouse model of overexpression of BMP4 and combined a model cell line commonly used in Alzheimer’s disease with N2 A cells,HT22 cells,and SH-SY5 Y cells for testing.(1)The BMP4 transgenic mice and wild mice according to the age of rat is divided into four 1,3,6,9 month age,mice hippocampus extract four ages of protein and RNA,immune protein imprinting and rt-pcr technique is used to inspect different ages in the hippocampus of AD diagnostic markers(beta amyloid,TAU protein and phosphorylation level)and the change of apoptosis.(2)Morris water maze experiment was used to verify whether the BMP4 overexpression transgenic mice had memory loss;(3)TUNEL fluorescence and HE staining were used to detect apoptosis and neuronal loss in hippocampus of aged mice aged 9 months;(4)The expression of RNA of BMP4 gene in three cell lines was detected by fluorescence quantitative PCR,BMP4 overexpression plasmid was constructed fromlow expression of BMP4 cell line,and BMP4 overexpression cell line was transfected with si-BMP4.The changes of AD protein markers and apoptosis in cell lines were observed by WB,RT-PCR,MTT cell proliferation experiments and flow cytometry to explore whether the level of BMP4 affected the progression of Alzheimer’s disease.Results:(1)The results of protein and RNA in hippocampus of NSE-BMP4 transgenic mice showed that the Aβ and Tau protein increased and the apoptosis of neurons increased.(2)NSE-BMP4 transgenic mice had some memory impairment compared with wild mice of the same age.(3)TUNEL experiment showed that NSE-BMP4 apoptosis rate of hippocampal CA1、CA3 and dentate gyrus was increased,and HE staining showed that the vertebral body cells in hippocampal CA1 and CA3 of transgenic mice were disordered,loose,decreased in cell layer nerve cell loss occurred.(4)Cell line experiments demonstrated that BMP4 expression was positively correlated with the expression levels of AD diagnostic markers(β amyloid and Tau proteins)and apoptosis.Conclusions:(1)BMP4 regulates the proteins Aβ and TAU,which are markers of alzheimer’s disease.(2)Overexpression of BMP4 may increase the risk of alzheimer’s disease.(3)BMP4 promotes neuronal apoptosis and inhibits nerve cell proliferation.