Effects of hypothyroidism upon the granular layer of the dentate gyrus in male and female adult rats: a morphometric study.

The effects of hypothyroidism upon the structure of the central nervous system of adult rats are poorly understood in spite of evidence that the mature brain is vulnerable to this condition. Existing developmental studies show that the morphological changes induced by thyroid hormone deficiency are related to alterations in neurogenesis. We studied the granular layer of the dentate gyrus under different experimental conditions of hypothyroidism, because in rodents the neurogenesis of the granule cells continues during adulthood. The following groups of rats were analysed: 1) control; 2) hypothyroid from day 0 until day 180 (hypothyroid group); 3) hypothyroid until day 30 and henceforth maintained euthyroid (recovery group); and 4) hypothyroid since day 30 (adult hypothyroid group). Groups of 6 male rats and 6 female rats were analysed separately. The volume of the dentate gyrus granular layer and the numerical density of its neurons were evaluated, so we were able to estimate the total number of granule cells. Because in the experimental groups the volume of the granular layer and the numerical density of its neurons were reduced, the total number of granule cells was decreased. In the hypothyroid and recovery groups the alterations were identical and more striking than in the adult hypothyroid groups. The total number of granule cells displayed sexual differences in all groups studied except in the hypothyroid groups. The present results support the view that thyroid hormone deficiency interferes with the process of cell acquisition by reducing neuronal proliferation and that it also leads to increased cell death. These events underlie the irreversible morphological changes observed in the brain of hypothyroid rats, either during development or at maturity. The referred structural alterations are probably related to the functional deficits observed in this condition.