mRNA Expression of Proteins Involved in Iron Homeostasis in Brain Regions is Altered by Age and by Iron Overloading in the Neonatal Period

Abstract

Abnormally high levels of iron are observed in the brain of patients suffering from neurodegenerative disorders. The mechanisms involved in iron accumulation in neurodegenerative disorders remain poorly understood. In the present study we investigated the effects of aging and neonatal iron overload on the mRNA expression of proteins critically involved in controlling iron homeostasis. Wistar rat pups received a single daily dose of vehicle or iron (10 mg/kg of b.w. of Fe(2+)), at postnatal days 12-14. The expression of Transferrin Receptor (TfR), H-Ferritin, and IRP2 were analyzed by a semi-quantitative reverse transcriptase polymerase chain reaction assay in cortex, hippocampus and striatum of rats sacrificed at three different ages (15-day-old; 90-day-old and 2-year old rats). Results indicate that TfR, H-ferritin, and IRP2 mRNA expression was differentially affected by aging and by neonatal iron treatment in all three brain regions. These findings might have implications for the understanding of iron homeostasis misregulation associated with neurodegenerative disorders.

Is early-life iron exposure critical in neurodegeneration?

“…Iron supplementation of the diet of neo natal rodents causes a permanent increase in iron levels in the brain, 48-50 alters expression of proteins involved in iron homeostasis, 51 decreases neuronal counts, increases astrogliosis, 52,53 and leads to motor and cognitive abnormalities in adulthood. 48,49 These findings suggest that the infant brain is less protected against systemic iron overload than is the adult brain.…”

“…No increase in iron levels in the brain at 10 weeks 10 weeks is a relatively young age to consider the effects of iron in the brain in relation to age-related neurodegeneration Acikoyl et al 51 Analysis of non-haem iron levels in the brains of TFR2 -/-mice aged 10 weeks…”

A fluorescence turn-off chemosensor based on N-doped carbon quantum dots for detection of Fe3+ in aqueous solution

“…The design and development of fluorescence sensors for the detection of Fe 3+ is becoming an important issue because of the vital roles Fe 3+ plays in environmental, biological, and chemical systems [1][2][3][4][5]. Recently, a large number of fluorescent chemosensors were exploited as useful tools for the detection of Fe 3+ owing to their intrinsic sensitivity, selectivity, and capacity for rapid, real-time monitoring [6][7][8][9][10].…”

Excess iron intake as a factor in growth, infections, and development of infants and young children

“…Although brain maturation in mice is quite different from that in human infants, the authors proposed that elevated neonatal iron intake may be a potential risk factor for later development of Parkinson disease. That early life iron exposure can have long-term consequences for brain iron homeostasis was shown by Dornelles et al (36) who analyzed the gene expression of transferrin receptor, H-ferritin, and iron regulatory protein 2 in the cortex, hippocampus, and striatum of rats who had been given 10 mg ferrous iron/kg body weight during PDs 12-14 when they were 15-d, 90-d, and 2-y old. All of these proteins that are involved in iron homeostasis regulation were dysregulated by early iron exposure, and the authors suggested that this involvement may explain the misregulation shown in neurologic disorders.…”