Kim, JonghanLi, YuanBuckett, PeterBöhlke, MarkThompson, KhristyTakahashi, MasayaMaher, Timothy J.Wessling-resnick, Marianne2012-12-182012Kim, Jonghan, Yuan Li, Peter D. Buckett, Mark Böhlke, Khristy J. Thompson, Masaya Takahashi, Timothy J. Maher, and Marianne Wessling-Resnick. 2012. Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency. PLoS ONE 7(3): e33533.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10058897Iron-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 onmotor impairment due to low iron status.en-USbiologybiochemistryneurochemistryneurochemicalsmoedel organismsanimal modelstoxicologymedicinenutritionradiologydiagnostic radiologyJournal Article2012-12-1810.1371/journal.pone.0033533