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Effect of propylthiouracil treatment during prenatal and early postnatal development on the neocortex of rat pups
M Behnam-Rassoli1, L C Herbert, V Howard
1Department of Human Anatomy and Cell Biology, University of Liverpool, UK.
Insights
A hypothyroid environment during development significantly reduces neocortex size in rats. Thyroid hormone supplementation partially reversed these effects, highlighting the critical role of thyroid hormones in brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Thyroid hormones are crucial for normal brain development.
- Disruptions in thyroid hormone levels during critical developmental periods can lead to long-term neurological deficits.
Purpose of the Study:
- To investigate the impact of a pre- and postnatal hypothyroid environment on neocortex development in rats.
- To determine if thyroid hormone supplementation can mitigate the effects of hypothyroidism on neocortex growth.
Main Methods:
- Rats were exposed to propylthiouracil (PTU) to induce hypothyroidism during pregnancy and early pup development.
- Thyroid hormones (T4 or T3) were administered to some PTU-treated rats.
- The Cavalieri method and disector particle-counting method were used to measure neocortex volume, glial cell numbers, and neuronal numbers.
Main Results:
- PTU treatment significantly reduced neocortex volume at all measured postnatal stages.
- Neuron numbers remained constant, but glial cell numbers were also affected by PTU.
- Thyroxine (T4) or tri-iodothyronine (T3) supplementation partially reversed the reduction in neocortex volume.
- The neuropile volume was more severely affected than neuron cell body volume.
Conclusions:
- A hypothyroid environment during development impairs neocortex growth, particularly affecting neuropile expansion.
- Thyroid hormone replacement therapy can partially restore normal neocortex development.
- These findings underscore the essential role of thyroid hormones for proper brain maturation.
Abstract:
The effects of a pre- and postnatal hypothyroid environment on the development of the neocortex have been determined. Rats were treated with propylthiouracil (PTU) with or without thyroid hormone supplementation during pregnancy and throughout the early development of the pups. The Cavalieri method was used to provide an estimate of the volume of the neocortex, and a combination of the Cavalieri method and the 'disector' particle-counting method provided an unbiased estimate of the numbers of glia and neurons in the neocortex. In pups from non-treated rats the mean volume of the neocortex increased from 31.3 mm3 at 5 days postnatally to 191.5 mm3 at 20 days and then remained constant to day 48. Similarly, the mean number of glial cells increased from 5.2 x 10(6) at day 5 to 12.0 x 10(6) on day 20 and then remained constant to day 48. The mean number of neurons in the neocortex in the control condition was constant at about 14.6 x 10(6) from day 5 to day 48. PTU treatment during pregnancy and postnatal development significantly decreased the mean volume of the neocortex at all of the stages studied, for example from 31.3 to 23.3 mm3 (p less than 0.001) on day 5 and from 191.5 to 155.0 mm3 (p less than 0.001) on day 20. Supplementation with thyroxine (T4) or tri-iodothyronine partially reversed this at certain stages. For example, the mean volume of the neocortex at 48 days was 197.5 mm3 in control rats, 118.1 mm3 in PTU-treated rats and 169.3 mm3 in PTU-treated rats supplemented with T4. Within the neocortex, the volume of the neuropile was more severely affected than was the volume of the neuron cell bodies.(ABSTRACT TRUNCATED AT 250 WORDS)