Effect of Olfactory Manganese Dose on Motor Coordination in Iron-Deficient Rats

Abstract

While exposures to excessive amount of metals increase brain damage, our recent study demonstrated that manganese (Mn) exposure corrected neurobehavioral problems resulting from iron deficiency in young rats. To further characterize the dose-dependent effect of intranasal manganese on motor coordination under iron deficiency, weanling rats were fed iron-deficient (5 mg iron/kg diet) or iron-adequate control diet (50 mg/kg) for 5 weeks and manganese chloride (MnCl2) solution was intranasal instilled through the right nostril twice a week for 3 weeks. Iron-deficient rats displayed lower blood hematocrit than controls, reflecting an iron-deficient anemic condition. Mn instillation did not alter hematocrit but modestly decreased body weight. In the rotarod test, Mn-instilled rats decreased motor coordination compared with water-instilled control rats (17% decrease in the time of the first drop; P=0.042). Iron-deficiency also decreases rotarod performance. However, upon Mn instillation, iron-deficient rats stayed longer on the bar by 30% than controls (P=0.006). Interestingly, the improvement in motor coordination was associated with manganese dose. Since both iron and Mn support tyrosine hydroxylase (TH), a critical enzyme in dopamine production, we tested if TH expression was modified by Mn instillation under iron deficiency. TH levels in the striatum were increased in iron deficiency and decreased upon Mn instillation, indicating that TH is unrelated with improved motor coordination in response to olfactory Mn under iron deficiency. Taken together, these results demonstrate that either olfactory Mn exposure or iron deficiency decreases motor function but a combination of the two restores poor motor performance by Mn dose-dependent manner.