HFE deficiency attenuates impulsivity induced by intranasal manganese (907.7)

HFE deficiency attenuates impulsivity induced by intranasal manganese Qi Ye and Jonghan Kim Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA While excessive manganese (Mn) alters emotion and mood, olfactory Mn transport is enhanced in Hfe deficiency, which is the major cause of iron overload hemochromatosis. Hence we investigated the effect of HFE on Mn‐related impulsivity using Hfe‐knockout (Hfe ‐/‐ ) and wild‐type (Hfe +/+ ) mice after intranasal instillation of MnCl 2 (5 mg/kg) daily for 3 wks. Mn‐instilled mice spent more time in open arms than water‐instilled mice in an elevated plus maze, indicating an increased impulsivity (p=0.024, n=10‐13). Upon Mn exposure, however, Hfe ‐/‐ mice entered the open arm later than Hfe +/+ mice (p=0.008), indicating that Mn‐induced impulsivity was corrected by Hfe deficiency. Since dopamine transporter (DAT) in the prefrontal cortex is involved in impulsivity, we conducted western blot and found that Mn instillation increased DAT levels in Hfe +/+ mice (1.3‐fold increase; p=0.004) but not in Hfe ‐/‐ mice. To further investigate if oxidative stress induced by metal exposure is associated with altered emotion, activities of superoxide dismutase (SOD), an anti‐oxidative enzyme, was evaluated. SOD activity was elevated in Hfe ‐/‐ mice(p<0.001), but reduced in Hfe +/+ mice (p=0.046) upon Mn exposure. Taken together, our results suggest that individuals with HFE deficiency could be less susceptible to airborne Mn‐induced impulsivity, likely due to altered dopamine signaling and enhanced protective activity of SOD. Grant Funding Source : NIH R00 ES017781