Sex Differences in the Cognitive and Hippocampal Effects of Streptozotocin in an Animal Model of Sporadic AD

More than 95% of Alzheimer's disease (AD) belongs to sporadic AD (sAD), and related animal models are the important research tools for investigating the pathogenesis and developing new drugs for sAD. An intracerebroventricular infusion of streptozotocin (ICV-STZ) is commonly employed to generate sporadic AD animal model. Moreover, the potential impact of sex on brain function is now emphasized in the field of AD. However, whether sex differences exist in AD animal models remains unknown. Here we reported that ICV-STZ remarkably resulted in learning and memory impairment in the Sprague-Dawley male rats, but not in the female rats. We also found tau hyperphosphorylation, an increase of Aβ40/42 as well as increase in both GSK-3β and BACE1 activities, while a loss of dendritic and synaptic plasticity was observed in the male STZ rats. However, STZ did not induce above alterations in the female rats. Furthermore, estradiol levels of serum and hippocampus of female rats were much higher than that of male rats. In conclusion, sex differences exist in this sporadic AD animal model (Sprague-Dawley rats induced by STZ), and this should be considered in future AD research.