title: Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency.
abstract: Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI). Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2) for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2). Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT) and dopamine receptor D(1) (D1R) levels were reduced and dopamine receptor D(2) (D2R) levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Jonghan
authors.initials: J
authors.lastname: Kim
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Peter D
authors.initials: PD
authors.lastname: Buckett
authors.forename: Mark
authors.initials: M
authors.lastname: Böhlke
authors.forename: Khristy J
authors.initials: KJ
authors.lastname: Thompson
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Maher
authors.forename: Marianne
authors.initials: M
authors.lastname: Wessling-Resnick
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D007322:Instillation, Drug; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D019266:Iron, Dietary; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000008:administration & dosage / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology*; D009830:Olfactory Bulb / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D019266:Iron, Dietary; D011954:Receptors, Dopamine; D008345:Manganese; D007501:Iron; D004298:Dopamine