Thyroid in Brain Part II

Then came the important-yet-could-be-perceived-as-cruel tests of their musculoskeletal function.  The normal mice (scientifically referred to as "wild-type", as in found in the "wild") and 2KO mice were made to walk on a rotating rod (Rotarod test) until they fell off.  They were also made to hang from a wire, and their grip strength was measured.  Guess who did better.

Overall, these mice seem to have a very similar profile as the MCT8-challenged humans, and offer a model to study further the effects of thyroid hormone transport.

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The third and last speaker compared the neurological outcomes of two different populations: babies born to under-treated hypothyroid mothers, and babies born without thyroids.  Babies as fetuses rely completely on their mothers for thyroid hormone.  They begin to make their own thyroid hormone in the second trimester, and rely more and more on their own thyroid than their mothers' until they reach independence at delivery.  (Thyroid independence only.  They're pretty much dependent on us for everything else). Anyhow, armed with this knowledge, we can classify these groups into early, fetal hypothyroidism (FH) and late, congenital hypothyroidism (CH).

FH was recently studied by Dr. Haddow (NEJM) which showed a direct correlation between maternal Free T4 and baby's IQ. If the mother's Free T4 was in the lowest 10%ile, the children did less well on the Bailey test (a tool used to objectively measure intelligence in kids).  If the low level persisted into the 3rd trimesters, IQ was further decreased.  Similar findings were seen in other cohorts (Project VIVA, "Maine", ABLD, and Generation R).

CH patients, even with optimal thyroid hormone replacement, have, on average, 7.5 fewer IQ points, and seem to struggle with visuospatial understanding and memory.

Now for some more mice studies.  In 2007, Dr. Mary Gilbert treated pregnant mice with an anti-thyroid drug called methimazole for 1-3 days (thereby making her hypothyroid) before replacing thyroid hormone afterward, effectively creating the same scenario as FH when done in early pregnancy, and similar to CH when done in later pregnancy.
Careful study of the FH pups revealed inadequate migration of the various brain cells in the hippocampus and cortex, leading to a thickened cortex.  Behaviorally, tFH mice were prone to seizures and "wild runs".  (Incidentally, I did not know running wildly about was bad, but in mice, apparently so.)

On anatomy studies, the development of the cortex (corticogenesis) was altered, with persistence of symmetric division of the progenitor cells, and less asymmetric division into more specified cells.  (Mohan 2012).

Back to the humans, CH and FH patients were noted to have alterations on MRI.  Older patients of both types had impaired memory of events in their own lives.

Overall, in both mouse and human models, both FH and CH caused independent problems in development of the human brain.