Sarah Magee

Sarah Magee

PI: Aaron Bowman, PhD, Department of Neurology and Pediatrics

Hepatic Ferroportin Expression Altered by HD and Mn Exposure 

Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disease caused by a mutation in the Huntingtin (HTT) gene; however, there are environmental modifiers of symptom onset. One such modifier is the essential metal Manganese (Mn) which is an essential cofactor for several metabolic processes within the brain. Mn deficits have been observed in in vivo and in vitro models of HD suggesting an impairment in Mn homeostasis. I hypothesize that HD animals will be less sensitive to the transcriptional effects of Mn in the liver compared to WT mice. To address this hypothesis, I utilized 12-week old, male YAC128Q mice containing mutant HTT and wild-type littermates. Mice received one subcutaneous injection of 13.88mg of Mn or water at 0hr, 1hr, 4hrs, 24hrs, and 1 week prior to sacrifice. At sacrifice, liver and brain samples were collected and halved. One half of each sample was used to isolate RNA and measure transcriptional differences using qRT-PCR. In the liver and brain, we measured several Mn-responsive genes including Ferroportin (FPN). We found that HD mice had 22% lower expression of FPN in the liver compared to WT mice (p<0.05).  Furthermore, immediately after Mn exposure, FPN expression increased by 40% (p < 0.05) in the liver of WT mice while having no effect in HD mice. Interestingly, FPN levels were not altered by Mn exposure in the brain of HD or WT mice. Our findings suggest that Mn homeostasis may be regulated differently by the liver of HD mice compared to WT mice.