Influence of Hfe on neurobehavior in 1‐year‐old mice JuOae Chang, Jonghan Kim Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA Mutations in HFE (hemochromatosis) gene are associated with neurodegenerative diseases with age. To better understand the effect of HFE on the age‐related neurobehavioral dysfunction, we conducted a series of behavior tests using 1‐yr‐old mice. Hfe‐deficient (Hfe‐/‐) and control wild‐type (Hfe+/+) mice showed similar performances in marble‐burying, elevated plus maze and rotarod, suggesting that Hfe deficiency does not affect emotional behavior or motor function over age. In contrast, Hfe‐/‐ mice spent less time around the target hole than wild‐type mice (5 vs 12 s; p=0.048) in the Barnes maze test, representing reduced spatial memory function upon Hfe deficiency. Since memory loss is associated with disrupted iron homeostasis in the brain, we determined metal concentrations using ICP‐MS. Compared with controls, Hfe‐/‐ mice had similar levels of Fe and other metals (Zn, Cu, Mn) in the brain, despite elevated non‐heme iron levels in other tissues, such as serum (70% increase), liver (170%), and kidney (40%; p<0.05 for all; n=7‐8/group). These results indicate that Hfe deficiency alters systemic iron status and not brain iron. Taken together, loss of Hfe function attenuates spatial memory capacity without altering iron in the brain, suggesting a possible role of Hfe in the memory process by an iron‐independent manner.Grant Funding Source: R00 ES017781