DEVELOPMENT OF (Na+‐K+)‐ATPase IN RAT CEREBRUM: CORRELATION WITH Na + ‐DEPENDENT PHOSPHORYLATION AND K +‐para NITROPHENYLPHOSPHATASE1

Intl J of Devlp Neuroscience

Incerpi²

2012

Administration of chemotherapy during pregnancy may represent a big risk factor for the developing brain, therefore we studied whether the transplacental transport of doxorubicin (DOX) may affect the development of neuroendocrine system. DOX (25 mg/kg; 3 times interaperitoneally/week) was given to pregnant rats during whole gestation period. The disturbances in neuroendocrine functions were investigated at gestation day (GD) 15 and 20 by following the maternal and fetal thyroid hormone levels, fetal nucleotides (ATP, ADP, AMP) levels and adenosine triphosphatase (Na(+), K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) activities in two brain regions, cerebrum and cerebellum. In control group, the levels of maternal and fetal serum thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), and fetal serum growth hormone (GH) increased from days 15 to 20, whereas in the DOX group, a decrease in maternal and fetal T4, T3 and increase in TSH levels (hypothyroid status) were observed. Also, the levels of fetal GH decreased continuously from GD 15 to 20 with respect to control group. In cerebrum and cerebellum, the levels of fetal nucleotides and the activities of fetal ATPases in control group followed a synchronized course of development. The fetal hypothyroidism due to maternal administration of DOX decreased the levels of nucleotides, ATPases activities, and total adenylate, instead, the adenylate energy charge showed a trend to an increase in both brain regions at all ages tested. These alterations were dose- and age-dependent and this, in turn, may impair the nerve transmission. Finally, DOX may act as neuroendocrine disruptor causing hypothyroidism and fetal brain energetic dysfunction.

Section: Discussionmentioning

confidence: 99%

Gestational doxorubicin alters fetal thyroid–brain axis

Intl J of Devlp Neuroscience

Incerpi²

2012

“…ATPase‐enzyme (Na + ,K + ‐ATPase, Ca 2+ ‐ATPase and Mg 2+ ‐ATPase) activities of control rat offspring were stepwisely increased in all investigated regions with the age progress. During development, there is an increase in Na + ,K + ‐ATPase activity in the rat brain (Bertoni and Siegel, 1978) accompanied by a marked change in the brain's ionic composition (Valcana and Timiras, 1969) and increase in the number of functional sodium pump sites (Bertoni and Siegel, 1978). Notably, Valcana and Timiras (1969) have shown that a component of the increase in Na + ,K + ‐ATPase activity in developing rat brain is due to the presence of THs.…”

Section: Discussionmentioning

confidence: 99%

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

El-Tawab

Intl J of Devlp Neuroscience

2010

125

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 50 microg to 200 microg/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, gamma-aminobutyric acid (GABA), acetylcholinesterase (AchE), ATPase-enzymes (Na(+),K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-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 hypert...

J of Neuroscience Research

“…A substantial amount of evidence demonstrates a relationship between cellular proliferation and maturation and the activity of the Na,K-ATPase (Kennedy and Lever, 1984;Smith and Rozengurt, 1978). The activity of this enzyme responsible for the active Na-K transport across the nerve cell membrane (Stahl, 1986) increases with neuronal differentiation (Atterwill et al, 1984;Bertoni and Siegel, 1978;Blanco and Beauge, 1988). Moreover, the relative expression of the various isoforms of the Na,K-ATPasc demonstrated in nervous tissue (Blanco and Beau&, 1988;Matsuda et al, 1984;Shull et al, 1986;Sweadner, 1989) seems to be dependent on the dcvelopmental stage (Blanco andBeauge, 1988: Matsuda et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Differentiation of rat hippocampal neurons induced by estrogen in vitro: Effects on neuritogenesis and Na,K‐ATPase activity

Blanco

Díaz

Carrer

et al. 1990

To gain insight into the mechanisms responsible for differentiation of hippocampal neurons growing in vitro, the effects of estrogen on neuritic development and on activity and distribution of isoforms of the Na, K-ATPase, were evaluated. Dissociated cells from hippocampi of 19-day-old rat fetuses were raised for 5 days in the presence or absence of 100 nM estradiol-17 beta (E2) in minimum essential medium supplemented either with 10% untreated fetal calf serum (MEM-10) or with 10% fetal calf serum previously adsorbed with dextran-activated charcoal (MEM-10-Cha). Cultures in MEM-10 showed larger neuritic length and increased levels of Na, K-ATPase activity than cultures in MEM-10-Cha. In cells cultured in MEM-10 medium, the addition of E2 resulted in selective enhancement of axonal length with a concomitant increase in the alpha-2 isoform of the Na, K-ATPase, whereas a decrease was found in the form most sensitive to ouabain; the total enzymatic activity remained unchanged. Conversely, in cultures raised in MEM-10-Cha, E2 did not affect Na, K-ATPase activity or neuritogenesis. These results show that two presumably independent probes of cellular differentiation of hippocampal neurons (i.e., neuritogenesis and patterns of Na, K-ATPase activity) were concurrently regulated by E2 and that such regulation depended on interaction with factor(s) present in calf serum. The well-known neuritogenic effect of E2 is hereby extended to hippocampal neurons, although for these cells it seems to be restricted to axons.