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OBJECTIVE Here we examined whether long-form PDE4Ds reversed memory impairment produced by Aβ1-42(Aβ42).METHODS Morris water-maze and novelty object recognition tests were used for memory measurements.Western blotting analysis was used for determination of the expression of CREB,pCREB,BDNF,IL-1β,TNF-α and NF-κB in order to explore the neurochemical mechanisms.RESULTS Aged Aβ42(0.5 μg/side) infused in bilateral dentate gyri produced memory deficits in the Morris water-maze(P<0.0001) and object recognition tests(P=0.0004) in mice.Microinfusions of lentiviral vectors containing miRNAs that target long-form PDE4D variants reversed Aβ42-induced memory deficits and concomitantly increased pCREB(P=0.0001) and BDNF(P<0.0001),and reduced inflammatory cytokines,including IL-1β(P=0.0026),TNF-α(P<0.0001),and NF-κB(P<0.0001) in the hippocampus of Aβ42-treated mice.CCONCLUSION These results suggest that long-form PDE4D variants maybe potential targets for treatment of memory loss associated with Alzheimer′s disease.
OBJECTIVE Here we examined whether long-form PDE4D knocked-in memory by Aβ1-42 (Aβ42) .METHODS Morris water-maze and novelty object recognition tests were used for memory measurements. Western blotting analysis was used for determination of the expression of CREB, pCREB, BDNF, IL-1β, TNF-α and NF-κB in order to explore the neurochemical mechanisms. RESULTS Aged Aβ42 (0.5 μg / side) infused in bilateral dentate gyri produced memory deficits in the Morris water- maze ) and object recognition tests (P = 0.0004) in mice. Microinfusions of lentiviral vectors containing miRNAs that target long-form PDE4D ieveralized mouse brain damage and concomitantly increased pCREB (P = 0.0001) and BDNF reduced inflammatory cytokines including IL-1β (P = 0.0026), TNF-α (P <0.0001), and NF-κB (P <0.0001) in the hippocampus of Aβ42-treated mice. CCONCLUSION These results suggest that long- form PDE4D variants maybe potential targets for treatment of memory loss associa ted with Alzheimer’s disease.