عنوان المقالة:O.M. Ahmed, R.G. Ahmed, A.W. El-Gareib, A.M. El-Bakry, S.M. Abd El-Tawaba, 2012. Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: II-The developmental pattern of neurons in relation to oxidative stress and antioxidant defense system. Int. J. Dev. Neurosci. 30, 517–537.
Excessive concentrations of free radicals in the developing brain may lead to neurons maldevelopment
and neurons damage and death. Thyroid hormones (THs) states play an important role in affecting the
modulation of oxidative stress and antioxidant defense system. Thus, the objective of this study was to
clarify the effect of hypothyroidism and hyperthyroidism in rat dams on the neurons development of
different brain regions of their offspring at several postnatal weeks in relation to changes in the oxidative
stress and antioxidant defense system. The adult female rats were administered methimazole (MMI) in
drinking water (0.02% w/v) from gestation day 1 to lactation day 21 to induce hypothyroidism and exogenous
thyroxine (T4) in drinking water (0.002% w/v) beside intragastric incubation of 50––200 T4 g/kg
body weight (b. wt.) to induce hyperthyroidism. In normal female rats, the sera total thyroxine (TT4) and
total triiodothyronine (TT3) levels were detectably increased at day 10 post-partum than those at day 10
of pregnancy. Free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone
(GH) concentrations in normal offspring were elevated at first, second and third postnatal weeks in an
age-dependent manner. In hypothyroid group, a marked depression was observed in sera of dam TT3
and TT4 as well as offspring FT3, FT4 and GH, while there was a significant increase in TSH level with the
age progress. The reverse pattern to latter state was recorded in hyperthyroid group. Concomitantly, in
control offspring, the rate of neuron development in both cerebellar and cerebral cortex was increased in
its density and complexity with age progress. This development may depend, largely, on THs state. Both
maternal hypothyroidism and hyperthyroidism caused severe growth retardation in neurons of these
regions of their offspring from the first to third weeks. Additionally, in normal offspring, seven antioxidant
enzymes, four non-enzymatic antioxidants and one oxidative stress marker (lipid peroxidation,
LPO) followed a synchronized course of alterations in cerebrum, cerebellum and medulla oblongata. In
both thyroid states, the oxidative damage has been demonstrated by the increased LPO and inhibition of
enzymatic and non-enzymatic antioxidants in most examined ages and brain regions. These disturbances
in the antioxidant defense system led to deterioration in the neuronal maturation and development. In
conclusion, it can be suggested that the maldevelopment of neurons and dendrites in different brain
regions of offspring of hypothyroid and hyperthyroid mother rat dams may be attributed, at least in part,
to the excess oxidative stress and deteriorated antioxidant defense system in such conditions.
تاريخ النشر
30/04/2012
الناشر
Int. J. Dev. Neurosci.
رابط DOI
http://dx
الكلمات المفتاحية
Development
Hypothyroidism
Hyperthyroidism
Neurons
Reactive oxygen species generation and
antio
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