Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types

[helvella]

This paper highlights the importance of T3 (Triiodothyronine) in development of the brain.

It makes me re-question the dependence on levothyroxine monotherapy in those born without thyroids. Can it possibly make sense?

Cereb Cortex. 2015 Nov 2. pii: bhv273. [Epub ahead of print]

Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.

Gil-Ibañez P1, García-García F2, Dopazo J3, Bernal J1, Morte B4.

Author information

1Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain Center for Biomedical Research on Rare Diseases, Madrid, Spain.

2Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.

3Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain Functional Genomics Node, INB at CIPF, Valencia, Spain.

4Center for Biomedical Research on Rare Diseases, Madrid, Spain.

Abstract

Thyroid hormones, thyroxine, and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation, we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way, we could identify targets of T3 within genes enriched in astrocytes and neurons, in specific layers including the subplate, and in specific neurons such as prepronociceptin, cholecystokinin, or cortistatin neurons. The subplate and the prepronociceptin neurons appear as potentially major targets of T3 action. T3 upregulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport and downregulates genes involved in nuclear events associated with the M phase of cell cycle, such as chromosome organization and segregation. Remarkably, the transcriptomic changes induced by T3 sustain the transition from fetal to adult patterns of gene expression. The results allow defining in molecular terms the elusive role of thyroid hormones on neocortical development.

© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [e-mail].

KEYWORDS:

development; gene regulation; subplate; thyroid hormones; transcriptomics

PMID:

26534908

[PubMed - as supplied by publisher]

ncbi.nlm.nih.gov/pubmed/265...

[RedApple Administrator]

Pass me some T3 please... my brain needs it even to be able to read the title of this paper

[SAMBS]

good thinking Helvella, genetics definitely play a part, as happened to me with my infected gland neck operation as a baby, and my thyroid seemingly was disturbed or whatever, almost before it had a chance to start working properly!

I've also signed up to the new NHS scheme, where I can record known health conditions, and can also apply for my complete NHS records, aT a price which will be well worth paying for!

I also want to apply for my father's health records but as was born in Scotland, lived in england after WW2' then moved back to and died in Scotlnd, don't know yet if NHS S Scotland will also run a similiR system, as I want to also apply for his health records, I don't know enough about my birth mothers whole life, but to best of my knowledge from the few months I met up with and knew her when in my 30's there didn't seem to be any complicated medical history there - I know she died of heart failure only, several years prior to my dad.

[helvella Administrator in reply to SAMBS]

Woudl you tell us more about the new NHS scheme?

[SAMBS in reply to helvella]

morning Helvella, It came from a link that was on one post reply on here or Headway, but I think here last week and so you know I'm not ignoring your Q I'll try and find the bookmark now and come back to this ASAP.

[SAMBS]

I'm so shattered now - just off to watch and listen to QT on TV! Nite nite all sleep well x

[Heloise]

Do you think that conversion would not supply enough T3 to the brain?

I know a person whose child had a thyroid problem as an infant. I never asked about the diagnosis but she developed cretinism. I wouldn't say she isn't as intelligent but she has a large skull and some sort of speech impairment. She is of normal height, She was born in the fifties so I assume she was given T4 and takes Synthroid now. I wonder if T3 would have been better.

This is one definition of cretinism.

Abstract

Cretinism is marked by irreversible mental and growth retardation. We describe here an entirely new case of cretinism showing combined pituitary hormone deficiencies of thyrotropin, growth hormone and prolactin that appears to be caused by homozygosity for a nonsense mutation in the gene for the pituitary specific transcription activator, Pit-1/GHF-1 (designated PIT1 in humans for pituitary specific factor 1). This is the first report in humans of a defect in a transcription activator causing deficiency of multiple target genes.

[helvella Administrator in reply to Heloise]

It isn't so much that I think conversion would not supply enough T3. More a case that monotherapy with T4 needs to be proved sufficient. And that sufficiency may depend on other factors - e.g. DIO2 gene.

However, even if T4 monotherapy is proved inadequate, just throwing in a daily dose of T3 as well might not be good enough. The whole system is very delicate and it might be that a more subtle approach is needed such as an implantable depot which slowly releases T3.

[Hidden]

Helvella,

I can so believe this .. not that I understand all the detailed processes recorded in the article above .. just the general gist.

T3 is so unbelievably vital and not just in the forming of us.

As an adult adding T3 it has had a profound effect on my fully developed brain.

Not only has it woken it up making it sharp and assertive but it has changed me psychologically too. ie .. calm, confident & an ability to concentrate (best bit. .. coz now I can read.. ! ! .) ..

Flo

[wano in reply to Hidden]

What kind of T3 do you use? Are there many different types?

[Hidden in reply to wano]

Wano,

T3 is T3 but each make uses different fillers, etc. There is also talk of varying strengths. Members talk of functioning well on one type but not another.

I am not really the person to ask as have only been medicating on T3 for four months and am prescribed Mercury Pharma on the NHS.

It has suited me well and changed my life.

Flower

[loueldhen]

How do we get this stuff into the British Thyroid Association? Am I right in understanding that they are the gatekeepers to prescribing treatment? I just read their 2015 guideline update which Shaws posted yesterday (as it's buried on their website). My T3 level wasn't tested in the 10 years I was on T4 therapy. First time was when I was moved to T3.