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.

Hallervorden-Spatz Syndrome: Case Report of a Typical Form

Hallervorden-Spatz syndrome is a rare neurodegenerative disease, related to mutations in a gene located on chromosome 20p13. Hallervorden-Spatz syndrome is characterized by iron accumulation in the basal ganglia, which leads to variable neurologic manifestations. It is reported the case of a 6 years old male patient, with history of neuro psycho motor development involution noticed since 1 year and 5 months of age and progressive development of dystonia, mostly on upper limbs and neck. Brain Magnetic Resonance Imaging (MRI) revealed bilaterally symmetric signal changes in globus pallidus and in the posterior limb of the internal capsule, findings that suggest neurodegenerative disease with iron accumulation or metabolic disease.