However, viral knockdown of neuronal BDNF in the hippocampus of APP/PS1 mice (in the absence of BFCN loss) neither increased the level of Aβ nor caused cognitive deficits.
Likewise, NOX activity and expression of the specific NOX subunit NOX4 were significantly increased in APP×PS1 mice in an age-dependent manner, and NOX activity and cognitive impairment shared a significant linear relationship.
Using a gene therapy approach, here we show that increasing brain p62 expression rescues cognitive deficits in APP/PS1 mice, a widely used animal model of AD.
<b>Conclusion</b>: These results suggest that UTI inhibits neuronal apoptosis in rat brain by attenuating increased expression of Aβ<sub>42</sub> and inflammatory cytokines, which may contribute to its alleviation of isoflurane-induced cognitive dysfunction in rats.
This "accelerated aging" with regard to hippocampal PEP expression in young APP transgenic mice might be one factor contributing to the observed cognitive deficits in these mice in the pre-plaque phase and could also explain in part the cognition-enhancing effects of PEP inhibitors in several experimental paradigms.
Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice.
At 9 months of age, untreated 3×Tg-AD mice vs. wild-type (WT) controls displayed cognitive deficits in behavioral assays and, at 12 months, elevated levels of hippocampal amyloid beta-protein (Aβ), amyloid precursor protein (APP), tau phosphorylation, and pro-inflammatory cytokines.