Aging is associated with increased brain iron through cortex-derived hepcidin expression

Iron is an essential molecule for biological processes, but its accumulation can lead to oxidative stress and cellular death. Due to its oxidative effects, iron accumulation is implicated in the process of aging and neurodegenerative diseases. However, the mechanism for this increase in iron with aging, and whether this increase is localized to specific cellular compartment(s), are not known. Here, we measured the levels of iron in different tissues of aged mice, and demonstrated that while cytosolic non-heme iron is increased in the liver and muscle tissue, only the aged brain cortex exhibits an increase in both the cytosolic and mitochondrial non-heme iron. This increase in brain iron is associated with elevated levels of local hepcidin mRNA and protein in the brain. We also demonstrate that the increase in hepcidin is associated with increased ubiquitination and reduced levels of the only iron exporter, ferroportin-1 (FPN1). Overall, our studies provide a potential mechanism for iron accumulation in the brain through increased local expression of hepcidin, and subsequent iron accumulation due to decreased iron export. Additionally, our data support that aging is associated with mitochondrial and cytosolic iron accumulation only in the brain and not in other tissues.

Analysis of deep grey nuclei susceptibility in early childhood: a quantitative susceptibility mapping and R2* study at 3 Tesla

Purpose Aging is the most significant determinant for brain iron accumulation in the deep grey matter. Data on brain iron evolution during brain maturation in early childhood are limited. The purpose of this study was to investigate age-related iron deposition in the deep grey matter in children using quantitative susceptibility (QSM) and R2* mapping. Methods We evaluated brain MRI scans of 74 children (age 6–154 months, mean 40 months). A multi-echo gradient-echo sequence obtained at 3 Tesla was used for the QSM and R2* calculation. Susceptibility of the pallidum, head of caudate nucleus, and putamen was correlated with age and compared between sexes. Results Susceptibility changes in all three nuclei correlated with age (correlation coefficients for QSM/R2*: globus pallidus 0.955/0.882, caudate nucleus 0.76/0.65, and putamen 0.643/0.611). During the first 2 years, the R2* values increased more rapidly than the QSM values, indicating a combined effect of iron deposition and myelination, followed by a likely dominating effect of iron deposition. There was no significant gender difference. Conclusion QSM and R2* can monitor myelin maturation processes and iron accumulation in the deep grey nuclei of the brain in early life and may be a promising tool for the detection of deviations of this normal process. Susceptibility in the deep nuclei is almost similar early after birth and increases more quickly in the pallidum. The combined use of QSM and R2* analysis is beneficial.

Evaluation of brain iron content in Egyptian Patients with Sickle cell disease and its impact on Neurocognitive functions

Background Sickle cell disease (SCD) is considered the most prevalent monogenic diseases worldwide. Iron overload is one of the major complications in those patients, especially who in need for frequent transfusion, affecting many organs including the brain. MRI is a valuable, reliable and non-invasive method for quantifying iron concentration in many organs as the liver and heart and it is now used for monitoring of the chelation therapy in SCD patients. Several studies began reporting differences in global cognitive function, particularly for children with SCD, they are at a high risk for neurocognitive impairment they often scored lower on general IQ measures than healthy children which is due to iron overload in brain tissue from the chronic transfusions which can lead to strokes and may be a silent stroke. Objective The current study assessed brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI study in SCD patients in comparison to age and sex-matched healthy controls. Methods A case-control study recruited 32 patients with SCD and 11 healthy controls. Brain MRI study using multi-echo fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated for only 15 SCD patients and the 11 controls. All recruited SCD patients and controls were examined for the neurocognitive functions by these tests: Wechsler IV Intelligence Scale for Adult shows (Verbal, Perceptual, Memory, Processing and Total IQ), their all normal values between 90 – 110. Benton Visual Retention Test have cut of point at (> 4 or = 4). Those values are the same for the difference between the obtained correct and the expected correct, and the difference between the obtained error and expected error. Results The fifteen patient with SCD who underwent brain MRI were age and sex matched with the eleven healthy control (15 SCD patients: mean-age: 16.93 ± 3.41 years, 40.6% females and 11healthy controls: mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. As regards the brain MRI, there was no statistically significant differences between SCD and control group in all regions of interests (p > 0.05). Our study showed that 72.7% of our SCD patients had under threshold TIQ scores. Also18% of the patients showed moderate anxiety, 9% mild anxiety and 9% showed severe anxiety. Conclusion The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur.