Overexpression of neuroglobin attenuates Aβ-induced apoptosis in brains of double transgenic AD mice

AIM: To observe the effects of neuroglobin(NGB) overexpression on the apoptosis induced by Aβ in the brains of double transgenic AD(APPswe/PS1dE9) mice and to explore its potential mechanisms.METHODS: Twenty-four 13-month-old double transgenic AD mice were randomly divided into 3 groups:intracerebroventricular injection with normal saline(NS) group, intracerebroventricular injection with pcDNA3.1 and NS group, and intracerebroventricular injection with pcDNA3.1 and pNGB group. Immunohistochemistry was used to detect the expression of Aβ_1-42 in the brains. TUNEL staining was used for analyzing the apoptosis, and the protein levels of cleaved caspase-3, caspase-9, PI3K, Akt and p-Akt were determined by Western blot.RESULTS: After intracerebroventricular injection with pNGB, the areas of Aβ_1-42 in the hippocampus and cortex were decreased compared with NS group and pcDNA3.1+NS group(P<0.01). The TUNEL-positive staining cells in the pNGB group were less than those in NS group and pcDNA3.1 group(P<0.01). NGB overexpression attenuated the protein levels of cleaved caspase-3 and caspase-9(P<0.01), but induced the production of PI3K and p-Akt(P<0.01).CONCLUSION: Overexpression of pNGB significantly inhibits the generation of Aβ and attenuates the apoptosis induced by Aβ, indicating that NGB overexpression activates PI3K/Akt pathway and inhibits the production of cleaved caspase-3 and caspase-9, which were tightly related with apoptosis.