Iron is increased in the brains of ageing mice lacking the neurofilament light gene
Autoři:
James C. Vickers aff001; Anna E. King aff001; Graeme H. McCormack aff001; Aidan D. Bindoff aff001; Paul A. Adlard aff002
Působiště autorů:
Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Australia
aff001; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia
aff002
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0224169
Souhrn
There has been strong interest in the role of metals in neurodegeneration, and how ageing may predispose the brain to related diseases such as Alzheimer’s disease. Recent work has also highlighted a potential interaction between different metal species and various components of the cytoskeletal network in the brain, which themselves have a reported role in age-related degenerative disease and other neurological disorders. Neurofilaments are one such class of intermediate filament protein that have a demonstrated capacity to bind and utilise cation species. In this study, we investigated the consequences of altering the neurofilamentous network on metal ion homeostasis by examining neurofilament light (NFL) gene knockout mice, relative to wildtype control animals, at adulthood (5 months of age) and advanced age (22 months). Inductively coupled plasma mass spectroscopy demonstrated that the concentrations of iron (Fe), copper (Cu) and zinc (Zn) varied across brain regions and peripheral nerve samples. Zn and Fe showed statistically significant interactions between genotype and age, as well as between genotype and region, and Cu demonstrated a genotype and region interaction. The most substantial difference between genotypes was found in Fe in the older animals, where, across many regions examined, there was elevated Fe in the NFL knockout mice. This data indicates a potential relationship between the neurofilamentous cytoskeleton and the processing and/or storage of Fe through ageing.
Klíčová slova:
Aging – Alzheimer's disease – Brain diseases – Cations – Neural networks – Neurons – Zinc – Iron
Zdroje
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