The effect of prenatal procarbazine treatment on brain development in the rat

Groups of pregnant Sprague-Dawley rats were treated orally with procarbazine, an antineoplastic drug, at dose levels of 0, 1.0, 2.5, 5.0, 7.5, and 10.0 mg/kg/day from days 12 through 15 of gestation. Following normal delivery, offspring were raised until day 21 and sacrificed, and their brains removed and weighed. A dose-dependent micrencephaly, characterized by hypoplasia of the cerebral hemispheres, was seen starting at 2.5 mg/kg/day. In a second study, groups of pregnant female rats were given a single dose of 10 mg/kg procarbazine on gestation day 12, 13, 14, or 15. Micrencephaly occurred in 21-day-old offspring from all groups, with the greatest effect induced on days 13, 14 and 15. Analysis of brain region weights revealed a maximum reduction in neocortex weight in offspring from groups treated on days 13 and 14. The hippocampus, cerebellum, and diencephalon-midbrain were also reduced in size, depending on the day of treatment, while the corpus striatum and pons-medulla were spared. In a final study, embryos from females treated on gestation days 12 through 15 were removed, fixed, and sectioned at 24-hour intervals starting on gestation days 13. Necrosis and cellular degeneration were observed with decreasing severity in the telencephalon, diencephalon, mesencephalon, and medulla. The neocortex of 20-day treated fetuses was characterized by a thickening of the ventricular zone and reduced cellularity of the cortical plate.     

The effect of phenylpyruvate on pyruvate metabolism in rat brain

1. The effect of phenylalanine and phenylpyruvate on the metabolism of pyruvate by isolated mitochondria from rat brain was investigated. 2. Phenylpyruvate inhibited the fixation of H(14)CO(3) (-) in the presence of pyruvate by intact rat brain mitochondria, whereas phenylalanine and other metabolites of this amino acid had no inhibitory effect on this process. 3. Pyruvate carboxylase activity in freeze-dried rat brain mitochondrial preparations was also inhibited only by phenylpyruvate, and a ;mixed type' inhibition was observed. 4. The K(m) for pyruvate of rat brain pyruvate carboxylase was about 0.2mm. 5. The concentration of phenylpyruvate required for a 50% inhibition of H(14)CO(3) (-) fixation by the intact mitochondria and of pyruvate carboxylase activity was dependent on the concentration of pyruvate used in the incubation medium. 6. The possible significance of inhibition of pyruvate carboxylase activity by phenylpyruvate in the brains of phenylketonuric patients is discussed.     

The effect of propranolol on rat brain catecholamine biosynthesis

The effect of propranolol on the levels of catecholamine in different parts of rat brain has been studied. The catecholamine contents of different regions were lowered by the drug. Dopamine Β-hydroxylase activity was also reduced, bothin vivo andin vitro. Propranolol is taken up by the brain tissue and the uptake is time-dependent. These results suggests that reduction in brain catecholamine levels and dopamine Β-hydroxylase activity may be one of the possible ways through which the drug manifests its clinical effects. C.D.R.I. Communication No. 3053.     

The effect of maternal and fetal corticosteroids on the development of function of the pituitary-adrenocortical system.

The pituitary-adrenocortical system of rat fetuses was stimulated (larger adrenals at birth) by maternal adrenalectomy, or suppressed (smaller adrenals at birth) by implantation of an ACTH secreting pituitary tumor (MtTF4). Offspring were delivered by caesarean section and fostered to untreated females. Offspring of intact females delivered by caesarean section and normally delivered offspring of intact mothers both fostered to untreated lactating females served as controls. Body growth in the first three weeks of life was delayed in offspring of tumor bearing mothers in Control-fostered subjects as compared to the 2 other groups. At 70 days of age female offspring of the tumor implanted and adrenalectomized mothers, as well as the Control-caesarean females, had smaller adrenals than Control-fostered animals of the same sex. The adrenal size of males was not significantly affected. No significant differences were found in resting concentrations of corticosterone in plasma, although offspring of adrenalectomized mothers had high values. Suppressed adrenal response to ether stress was found in offspring of tumor bearing mothers. The supposition is that interference with maternal pituitary-adrenocortical activity during pregnancy has a long lasting effect on fetal hypothalamo-pituitary-adrenocortical system.     

The effects of malnutrition on the prenatal development of rat brain]

Female rats were submitted to caloric and protein restriction 8 days before fecondation and during pregnancy. A reduction of the number of brain cells in the fetuses was evident only after the 20th day of pregnancy. This reduction appeared to be limited to glial cells, and not to affect neurons contrarily to what had previously been stated by some authors.     

The effect of phospholipids on the in vitro polymerization of rat brain tubulin

The association of brain tubulin, as measured by the temperature-dependent development of turbidity at 350 nm, is greatly stimulated by the detergent Nonidet P-40 in crude extracts of rat brain tissue. Stimulation of turbidity development is also obtained with partially purified rat brain tubulin treated with Nonidet or other detergents, or preincubated with phospholipase C or D; treatment with bovine pancreatic phospholipase A₂ produces an inhibition. Exogenous phospholipids, diglycerides, other related derivatives, and lipophilic extracts of tubulin and brain supernatants can also alter the turbidity development. In addition, microtubules arising from tubulin obtained in the presence of Tween-20 or Nonidet P-40 exhibit a 50 and 100% increased specific viscosity, respectively, over that of tubulin prepared in the absence of detergent or in the presence of Kyro or Triton N-101. The effectiveness of these detergents in removing phospholipids from tubulin preparations follows a similar pattern: Nonidet P-40 removes 80%, Tween-20 removes 50%, and Kyro or Triton N-101 removes none. The total mass of microtubule formed, as determined by sedimentation, is the same regardless of the effect of the detergents on the viscosity. The microtubules obtained in the presence of Nonidet P-40 have a normal appearance when examined by electron microscopy, and their composition on sodium dodecyl sulfate-polyacrylamide gel electrophoresis is indistinguishable from that of standard tubulin, especially with regard to the minor protein bands always present in the tubulin preparations. The results obtained suggest that the phospholipids associated to brain tubulin preparations might have a role in determining the association of tubulin and/or the final dimensions of the assembled microtubules.     

The effect of juglone on cholinergic mechanisms in rat brain synaptosomes

Juglone 5-hydroxy-1,4-napthoquinone exerts three activities on cortical synaptosomal preparations. It inhibits the release of acetylcholine and is an even more potent inhibitor of high-affinity choline transport into synaptosomes. In addition, as has already been shown by others using brain homogenates, juglone inhibits choline acetyltransferase.     

Neonatal neural organizing effects of exogenous corticosteroids on sexual differentiation of the brain in the female rat

Testosterone, deoxycorticosterone, or vehicle was administered neonatally to female Long-Evans rats. Parameters expressing the reproductive physiology and behavior of the adult animals were studied. It was found that neonatal administration of testosterone produced the expected "defeminization" and "masculinization" of the brain, affecting both the reproductive behavior and cyclicity of these females. In contrast, neonatal administration of the adrenal steroid did not affect cyclicity although it "defeminized" and "masculinized" sexual behavior, albeit to a lesser degree than testosterone. The results suggest a dichotomy in the neuroregulation of reproductive physiology and sexual behavior.     

The effect of irradiation on dopamine level and metabolism in the rat brain

In experiments on rats it was shown that after 20 Gy irradiation dopamine and homovanilic acid content increases in the caudate nucleus and limbic structures of the forebrain: dopamine disappears more readily when its biosynthesis is blocked. The rate of the mediator degradation in the brain increases by 1.5-2 times, and the rate of the synthesis, by 3-5 times at early times after irradiation.