Overexpression of neuroglobin attenuates Aβ-induced apoptosis in brains of double transgenic AD mice / 中国病理生理杂志

ABSTRACT

AIM:To observe the effects of neuroglobin ( NGB) overexpression on the apoptosis induced by Aβin 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 groupsintracerebroventricular 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 Aβ1-42 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 Aβ1-42 in the hippocampus and cortex were decreased compared with NS group and pcDNA 3.1+NS group (P<0.01).The TUNEL-positive staining cells in the pNGB group were less than those in NS group and pcDNA 3.1 group ( P<0.01 ) . NGB overexpression attenuated the protein levels of cleaved caspase-3 and caspase-9 (P<0.01), but induced the produc-tion of PI3K and p-Akt (P<0.01).CONCLUSION:Overexpression of pNGB significantly inhibits the generation of Aβand attenuates the apoptosis induced by Aβ, indicating that NGB overexpression activates PI 3K/Akt pathway and inhibits the production of cleaved caspase-3 and caspase-9, which were tightly related with apoptosis .