Genome-wide microarray analysis of brain gene expression in mice on a short-term high iron diet.
The effects of systemic iron overload on the brain are unclear. Microarray analysis of brain gene expression in mice following short-term iron supplementation revealed altered expression of 287 genes, although most changes were small. Transcripts for the iron storage protein ferritin light chain increased 20% (p=0.002) and transcripts for iron regulatory protein 1, which negatively regulates ferritin translation, decreased 28% (p=0.048). There were expression changes for genes involved in important brain functions such as neurotransmission and nitric oxide signaling, which is dependent on iron. Few changes related to reactive oxygen species, inflammation or apoptosis, however expression changes were observed for genes causatively linked to neurological disorders, including Charcot-Marie-Tooth disease, neuronal ceroid lipofuscinosis and mucolipidosis. The latter involve intralysosomal lipofuscin build-up that may reflect lysosomal iron accumulation. The findings suggest that high iron intake may cause subtle brain effects of clinical relevance in some circumstances.
Johnstone
Daniel
D
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia.
Milward
Elizabeth A
EA
D000818:Animals; D001052:Apoferritins / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics; D019266:Iron, Dietary / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D009422:Nervous System Diseases / Q000235:genetics; D009569:Nitric Oxide; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics
D019266:Iron, Dietary; D012333:RNA, Messenger; D009569:Nitric Oxide; D001052:Apoferritins; D007501:Iron