AUTHOR=Guo Chuang , Zhang Yu-Xin , Wang Tao , Zhong Man-Li , Yang Zhao-Hui , Hao Li-Juan , Chai Rui , Zhang Shuai TITLE=Intranasal deferoxamine attenuates synapse loss via up-regulating the P38/HIF-1α pathway on the brain of APP/PS1 transgenic mice JOURNAL=Frontiers in Aging Neuroscience VOLUME=7 YEAR=2015 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2015.00104 DOI=10.3389/fnagi.2015.00104 ISSN=1663-4365 ABSTRACT=
The widely recognized neuroprotective effect of iron chelators is contributed by their ability to prevent reactive oxygen species (ROS) generation via the Fenton reaction, which sequesters redox-active Fe. An additional neuroprotective mechanism of iron-chelating compounds is to regulate the transcriptional activator hypoxia-inducible factor 1α (HIF-1α). In the present study, we observed that intranasal administration of deferoxamine decreased beta-amyloid (Aβ) deposition and rescued synapse loss in the brain of Aβ precursor protein and presenilin-1 (APP/PS1) double transgenic mice. We found that deferoxamine (DFO) up-regulated HIF-1α mRNA expression and its protein level, and further induced the proteins that are encoded from HIF-1-adaptive genes, including transferrin receptor (TFR), divalent metal transporter 1 (DMT1), and brain-derived neurotrophic factor (BDNF). The effects of DFO on the induction and stabilization of HIF-1α were further confirmed