Gender differences in sensitivity and toxicokinetics of multiple metals have been identified in humans. A recent study suggested that young girls performed worse on intellectual exams than young boys exposed to manganese (Mn) in the environment. Animal studies have shown that Mn exposure causes differential effects on behavior in male compared to female mice. We hypothesized that in response to Mn exposure striatal Mn accumulation and/or striatal medium spiny neuron (MSN) morphology show gender-dependent effects. We evaluated the contribution of gender to neuropathology by examining striatal MSN morphology in male and female mice exposed to Mn. We found that gender played a significant role in alterations of striatal MSN morphology in mice exposed to Mn. Gender-dependent changes were strongest when striatal Mn levels were elevated 24h following the final Mn exposure. Nevertheless, gender-dependent alterations in neuron morphology were still present 3 weeks after the final Mn exposure. Gender differences in neuron morphology were not due to differential striatal Mn accumulation between genders. We conclude that although gender does not affect striatal Mn accumulation, MSN morphology is differentially sensitive to elevated Mn levels.
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