Gender differences in brain susceptibility to oxidative stress are mediated by levels of paraoxonase-2 expression

► Paraoxonase 2 (PON2) is expressed at higher levels in astrocytes and neurons from female mice. ► Brain cells from male mice are more susceptible to oxidative stress-induced toxicity. ► Estradiol modulates PON2 expression in vitro and in vivo. ► Estradiol-induced neuroprotection is not present in cells from PON2-null mice.