Thyroid hormones control our everyday metabolism, but they're
already crucial before birth: they are essential for the development of
the organs, including the brain.
And when the transporters of these hormones are not functioning
properly, the consequences for the development of the cerebellum or 'the
little brain' are very serious. These are the findings of a study by
researchers from KU Leuven (University of Leuven, Belgium) and King's
‘When the transporters of thyroid hormones are not functioning properly, the consequences for the development of the cerebellum or 'the little brain' are very serious.’
"These hormones ensure that different
cell types originate in the brain at the right moment, move to the right
place, and make the right connections," explains Professor Veerle
Darras from the Lab of Comparative Endocrinology at KU Leuven. "Until
the thyroid is fully developed, a fetus depends on the mother's
hormones. If the mother-to-be doesn't produce enough thyroid hormones,
this has a negative impact on the brain development of the fetus from a
very early stage."
Determining whether the thyroid is properly functioning is typically
done by measuring the amount of hormones in the blood. Unfortunately,
this is not always a good indicator. "This proved to be the case with
the rare Allan-Herndon-Dudley syndrome (AHDS), a hereditary condition of
the nervous system that only affects boys. These children suffer from
severe mental retardation and locomotor deficits.
Doctors looked for
possible thyroid hormone deficiencies but, surprisingly, the level of
hormones in the blood was abnormally high. The problem turned out to be
in the transporters that bring the hormones from the blood to the inside
of the cell. Due to a genetic mutation an important transporter - MCT8 -
is deactivated in patients with AHDS."
To find out more about this mutation Professor Darras's team
examined what happens in a chicken embryo when this transporter is
deactivated in a part of the little brain, PhD student Pieter Vancamp
"The little brain is important for locomotion. A thyroid
hormone deficiency impairs its development, but the role of the
transporters was not yet known. In our study, we noticed relatively
quickly that some important proteins - necessary for the development of
brain cells - were not produced in sufficient amounts in the part of the
brain with no active transporter. In a later stage, we noticed that the
Purkinje cells - nerve cells located in the cortex of the little brain -
have less dendritic branches. Therefore, brain cell signalling goes
haywire, and problems arise in other cells as well."
The results show that thyroid hormones are essential for embryonic
development right from the start. "The earlier things go wrong, the
harder it is to repair the damage after birth. Newborns are always
screened for thyroid problems with the heel prick, but it's better to
test the mothers-to-be as early as possible.
Unfortunately, this does
not yet happen in all hospitals. For the Allan-Herndon-Dudley syndrome,
in particular, our study raises questions about possible prenatal
treatments with variants of thyroid hormones: these can enter the cell
without the transporter. But this is still an experimental treatment -
one that is only being tested after birth."