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I did an expression profiling from publicly available RNAseq data for mouse tissues. While for liver and testes I am getting expected proteins in the top highly expressed mRNAs, for brain I am getting ferritin (Ferritin heavy chain 1: Fth1) as the top expressed mRNA!

There are a few studies which report elevated ferritin and iron in neurodegenerative diseases while some others have implicated its role in ageing.

I haven't come across any study on iron metabolism in the normal brain. Does iron metabolism play an important role in the function of the brain?

PS :

  • The data that I am talking about, has the SRA accession number- SRR652247 (I tried all three runs submitted in SRA)
  • The mice used in the experiment were 11 weeks old
  • I used bowtie -> eXpress for quantification of RNAseq reads.
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  • $\begingroup$ Look at the study summary - it describes expression profiling in testis. Do you think they might have mis-labeled the organ? $\endgroup$
    – MattDMo
    Jul 8, 2013 at 21:06
  • $\begingroup$ I don't think so.. because testes sample has high level of protamine expression which is not there in brain. Also, the highest expressed transcript (all RNAs) in brain is Bc1 - a ncRNA known to regulate translation at synapses. $\endgroup$
    – WYSIWYG
    Jul 9, 2013 at 3:53
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    $\begingroup$ As usual, association of NDD or age with Fe does not mean it's the causative agent, nor vice versa. $\endgroup$
    – R Stephan
    Jul 10, 2018 at 8:01

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Many articles focus on the pro-oxidant function of iron (and globins in particular). It makes sense that levels may be higher in the CNS due to their role in respiration, which is increased secondary to the “absolute requirement” for glucose facilitated by constitutive GLUT3 expression. So perhaps ferritin is increased to maintain supply for neuroglobin synthesis?

Another thing to consider, Ferroportin1 (FPN1) (iron export protein) is expressed at relatively low levels in the brain when compared to i.a. bone marrow (HPA 2018). You could hypothesise that increased storage is required as a result of decreased transport. But I would look at expression of import proteins; TFR, DMT1, and ZIP 8/14, as that could very quickly throw this theory off.

References:

The Human Protein Atlas (HPA) 2018, SLC40A1, The Human Protein Atlas, 11 September 2018, www.proteinatlas.org

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