title: Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis.
abstract: Manganese in excess promotes unstable emotional behavior. Our previous study showed that olfactory manganese uptake into the brain is altered in Hfe(-/-) mice, a model of iron overload hemochromatosis, suggesting that Hfe deficiency could modify the neurotoxicity of airborne manganese. We determined anxiety-related behavior and monoaminergic protein expression after repeated intranasal instillation of MnCl2 to Hfe(-/-) mice. Compared with manganese-instilled wild-type mice, Hfe(-/-) mice showed decreased manganese accumulation in the cerebellum. Hfe(-/-) mice also exhibited increased anxiety with decreased exploratory activity and elevated dopamine D1 receptor and norepinephrine transporter in the striatum. Moreover, Hfe deficiency attenuated manganese-associated impulsivity and modified the effect of manganese on the expression of tyrosine hydroxylase, vesicular monoamine transporter and serotonin transporter. Together, our data indicate that loss of HFE function alters manganese-associated emotional behavior and further suggest that HFE could be a potential molecular target to alleviate affective disorders induced by manganese inhalation.
authors.affiliation: Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA. Electronic address: j.kim@neu.edu.
authors.forename: Jonghan
authors.initials: J
authors.lastname: Kim
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D015306:Biogenic Monoamines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006432:Hemochromatosis / Q000523:psychology*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D008345:Manganese / Q000008:administration & dosage / Q000633:toxicity*; D018782:Maze Learning; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout
chemical_list: D015306:Biogenic Monoamines; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D008345:Manganese; D004298:Dopamine
keywords: Dopamine; Elevated plus maze; Impulsivity; Intranasal instillation; Norepinephrine; Serotonin