عنوان المقالة:Ahmed, O.M., Abd El-Tawab, S.M., Ahmed, R.G., 2010. Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: I- The development of the thyroid hormones-neurotransmitters and adenosinergic system interactions. Int. J. Dev. Neurosci. 28, 437-454.
The adequate functioning of the maternal thyroid gland plays an important role to ensure that the offspring
develop normally. Thus, maternal hypo- and hyperthyroidism are used from the gestation day 1
to lactation day 21, in general, to recognize the alleged association of offspring abnormalities associated
with the different thyroid status. In maternal rats during pregnancy and lactation, hypothyroidism in
one group was performed by antithyroid drug, methimazole (MMI) that was added in drinking water at
concentration 0.02% and hyperthyroidism in the other group was induced by exogenous thyroxine (T4)
(from 50g to 200g/kg body weight) intragastric administration beside adding 0.002% T4 to the drinking
water. The hypothyroid and hyperthyroid states in mothers during pregnancy and lactation periods
were confirmed by measuring total thyroxine (TT4) and triiodothyronine (TT3) at gestational day 10 and
10 days post-partum, respectively; the effect was more pronounced at the later period than the first. In
offspring of control maternal rats, the free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH)
and growth hormone (GH) concentrations were pronouncedly increased as the age progressed from 1
to 3 weeks. In hypothyroid group, a marked decrease in serum FT3, FT4 and GH levels was observed
while there was a significant increase in TSH level with age progress as compared with the corresponding
control. The reverse pattern to latter state was recorded in hyperthyroid group. The thyroid gland of
offspring of hypothyroid group, exhibited some histopathological changes as luminal obliteration of follicles,
hyperplasia, fibroblastic proliferation and some degenerative changes throughout the experimental
period. The offspring of hyperthyroid rats showed larger and less thyroid follicles with flattened cell
lining epithelium, decreased thyroid gland size and some degenerative changes along the experimental
period. On the other hand, the biochemical data revealed that in control offspring, the levels of iodothyronine
5-monodeiodinase (5-DI), monoamines, -aminobutyric acid (GABA), acetylcholinesterase (AchE),
ATPase-enzymes (Na+,K+-ATPase, Ca2+-ATPase and Mg2+-ATPase) follow a synchronized course of development
in all investigated brain regions (cerebrum, cerebellum and medulla oblongata). In addition, the
depression in 5-DI activity, monoamines levels with age progress in all investigated regions, was more
pronounced in hypothyroid offspring, while they were increased significantly in hyperthyroid ones in
comparison with their respective controls. Conversely, the reverse pattern was recorded in level of the
inhibitory transmitter, GABA while there was a disturbance in AchE and ATPases activities in both treated
groups along the experimental period in all studied regions. In conclusion, the hypothyroid status during
pregnancy and lactation produced inhibitory effects on monoamines, AchE and ATPases and excitatory
actions on GABA in different brain regions of the offspring while the hyperthyroid state induced a reverse
effect. Thus, the maternal hypothyroidism and hyperthyroidism may cause a number of biochemical disturbances
in different brain regions of their offspring and may lead to a pathophysiological state. These
alterations were age dependent.
تاريخ النشر
18/06/2010
الناشر
Int. J. Dev. Neurosci.
رابط DOI
doi:10.101
الكلمات المفتاحية
Development
Hypothyroidism
Hyperthyroidism
Neurotransmitters
Adenosinergic system
Ahmed R. G. | Ahmed R. G. | 2259