CNS neuroscience & therapeutics
-
Previously, we have documented that prenatal hypoxia can aggravate the cognitive impairment and Alzheimer's disease (AD) neuropathology in APP(Swe) /PS1(A246E) (APP/PS1) transgenic mice, and valproic acid (VPA) can prevent hypoxia-induced down-regulation of β-amyloid (Aβ) degradation enzyme neprilysin (NEP) in primary neurons. In this study, we have investigated the molecular mechanisms of VPA's anti-AD effects and found that VPA can reduce the prenatal hypoxia-induced neuritic plaque formation and improve the learning deficits in the AD mouse model. ⋯ Valproic acid is able to attenuate the prenatal hypoxia-induced Aβ neuropathology and learning and memory deficits via inhibiting the activation of histone deacetylase 1 (HDAC1), preventing the decrease in H3-Ace in the NEP promoter regions and reducing the down-regulation of NEP.