Effects of iron status and development on ferroportin and hepcidin gene expression in rat brain
Author
Boserup, Michael
Term
4. term
Publication year
2011
Submitted on
2011-06-01
Pages
37
Abstract
Jern er afgørende for sundhed, og både mangel og overskud kan give sygdom (for eksempel jernmangelanæmi eller hæmokromatose). Kroppen regulerer jern med proteiner som ferroportin, den eneste kendte jern-eksportør i pattedyr, og hepcidin, et peptid fra leveren, der mindsker jern tilgængelighed ved at udløse nedbrydning af ferroportin. Begge er påvist i hjernen. Dette studie undersøgte, hvordan udvikling (alder) og jernstatus påvirker genaktivitet (målt som mRNA-niveauer) for ferroportin og hepcidin i rottehjernens områder. I et udviklingsforsøg blev Wistar-rotter analyseret efter 2 uger, 8 uger og 8 måneder, med prøver fra cerebellum, ventral tegmental area (VTA) og habenula. I et jernstatusforsøg blev drægtige hunner gjort jernmangelfulde for at begrænse føtal jern; afkommet fik derefter enten jern- eller saltvandsinjektioner. Ved 8 ugers alder blev hunligt afkom undersøgt, inklusive hjerneområder (cerebral cortex, cerebellum, striatum, hjernestamme) og perifere væv (duodenum, første del af tyndtarmen, og lever). Aldring øgede jernkoncentrationer i hjernen, med højeste niveauer i cerebellum, mens ferroportin-genudtryk faldt i alle hjerneområder. Hepcidin mRNA var til stede i hjernen, men på meget lavt niveau, og alder ændrede det ikke signifikant. Jernstatus viste en tendens til ændret jernindhold i cortex, men ikke statistisk signifikant. Hos jernmangelfulde rotter var ferroportin-genudtryk højere i duodenum og lavere i leveren sammenlignet med jernsupplementerede dyr. Omvendt var ferroportin-udtryk i hjerneområderne uændret mellem jernmangelfulde, jern-reverterede og kontrolgrupper. Hepcidin mRNA var højere i lever og duodenum hos jernsupplementerede dyr end hos jernmangelfulde, mens hepcidin i hjernen forblev ekstremt lavt trods forskelle i hjernens jern. Samlet set påvirker udvikling og jernstatus genudtryk af ferroportin og hepcidin, og andre faktorer end hjernens jernindhold synes at regulere disse jerntransportmolekyler i hjernen.
Iron is vital for health, and both deficiency and excess can cause disease (for example, iron deficiency anemia or hemochromatosis). The body regulates iron using proteins such as ferroportin, the only known iron exporter in mammals, and hepcidin, a liver-made peptide that reduces iron availability by triggering ferroportin degradation. Both have been detected in the brain. This study examined how development (age) and iron status influence ferroportin and hepcidin gene activity (measured as mRNA levels) in rat brain regions. In a development experiment, Wistar rats were analyzed at 2 weeks, 8 weeks, and 8 months, with samples taken from the cerebellum, ventral tegmental area (VTA), and habenula. In an iron-status experiment, dams were made iron deficient during pregnancy to limit fetal iron; offspring then received either iron or saline injections. At 8 weeks, female offspring were analyzed, including brain regions (cerebral cortex, cerebellum, striatum, brain stem) and key peripheral tissues (duodenum, the first part of the small intestine, and liver). Aging increased brain iron concentrations, with the highest levels in the cerebellum, while ferroportin gene expression decreased across brain areas. Hepcidin mRNA was present in the brain but at very low levels, and age did not significantly change its expression. Iron status showed a trend in cortical iron content that was not statistically significant. In iron-deficient rats, ferroportin gene expression was higher in the duodenum and lower in the liver compared with iron-supplemented rats. In contrast, ferroportin expression in brain regions did not differ among iron-deficient, iron-reverted, and control groups. Hepcidin mRNA expression was higher in the liver and duodenum of iron-supplemented animals than in iron-deficient ones, while brain hepcidin remained extremely low despite differences in brain iron. Overall, development and iron status affect ferroportin and hepcidin gene expression, and factors beyond brain iron content likely influence how these iron transport molecules are regulated in the brain.
[This abstract was generated with the help of AI]
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