Experience-dependent regulation of vesicular zinc in male and female 3xTg-AD mice

In the mammalian cerebral cortex, zinc is an important modulator of synaptic transmission and conversely, plasticity. Zinc is also involved, in a sex-dependent manner, in the pathogenesis of Alzheimer's disease (AD), where substantial declines in plasticity may occur. To examine this relationship further, the regulation of vesicular zinc was examined after the induction of cortical plasticity through vibrissae plucking in male and female C57Bl/6 and 3xTg-AD mice at various age points. Female C57Bl/6 mice were found to have an elevated response compared to male C57Bl/6 mice through mid-adult ages, a sex-difference likely mediated by the differential regulation of vesicular zinc by the sex hormones. Male 3xTg-AD mice had a significantly greater zincergic response compared to C57Bl/6 mice, which is likely indicative of a compensatory mechanism utilized by the male 3xTg-AD mice to combat the decline in plasticity associated with the AD state. These results exemplify how the regulation of vesicular zinc may be a significant component in the progression of AD, especially regarding the sex-dependent element.