Teratopsychogenetic effects apparently produced by nonphysiological neurotransmitter concentrations during brain differentiation.

In male rats treated with pargyline, reserpine or pyridostigmine during neonatal life significant permanent changes of sexual behaviour and conditioned learning behaviour were observed in juvenile and/or adult life. Male sexual activity and learning capacity were permanently decreased in neonatally pargyline- or reserpine-treated animals, but permanently increased in neonatally pyridostigmine-treated rats. These findings suggest that nonphysiological concentrations and/or turnover rates of neurotransmitters, if produced during a critical period of brain differentiation, are able to induce lifelond effective behavioural changes, i.e. teratopsychogenetic effects.     

Apparent effects of neurotransmitters on sexual differentiation of the brain without mediation of sex hormones.

Male sexual behaviour was found to be permanently decreased in neonatally reserpinized or paragylinized male rats. On the other hand, hypoplasia of sex organs was only observed in reserpinized, but not in pargylinized newborn males. Furthermore, male sexual behavior was found to be permanently increased in neonatally pyridostigminized males which showed even a slight hypoplasia of seminal vesicles in neonatal life. These findings suggest that changes of neurotransmitter concentrations and/or turnover rates apparently induced by psychotrophic drugs can affect sex-specific brain differentiation by direct action without mediation of sex hormones. Hence, neurotransmitters may be regarded as organizers of the brain.     

Further evidence for a role of arachidonic acid in glucocorticoid teratogenic action in the palate

Arachidonic acid produces a significant reversal of the production of cleft palate by cortisone in the offspring of sensitive strains of mice in vivo. Arachidonic acid in nanogram per milliliter concentrations also produces a significant reversal of the cortisol inhibition of the programmed cell death of the medial edge epithelium of palatal shelves in vitro. This corrective action of arachidonic acid in vitro is significantly blocked by indomethacin at a nanogram per milliliter concentration which selectively inhibits the conversion of arachidonic acid to prostaglandins and/or thromboxanes at the level of cyclooxygenase. These results support the hypothesis that the inhibition of arachidonic acid release and subsequent prostaglandin and/or thromboxane production by glucocorticoids is involved in the teratogenic action of glucocorticoids and demonstrate that one site of this action is the inhibition of epithelial loss.     

Sex hormones and neurotransmitters as mediators for sexual differentiation of the brain

Sexual differentiation of the brain is regarded as a model for environment-dependent brain development mediated by systemic hormones and neurotransmitters. Abnormal concentrations of systemic hormones and/or neurotransmitters, if occurring during a critical period of brain development, can lead to permanent developmental disabilities of fundamental processes of life. Such developmental disabilities appear to be avoidable, at least in part, by improving the external, i.e. psychosocial and natural environment, or by correcting abnormalities in the internal, i.e. metabolic and hormonal environment and, particularly, by correcting abnormal neurotransmitter concentrations (and/or turnover rates) during brain development.     

Further evidence for early sex chromosome differentiation of Anuran species

Chromosome banding and meiotic evidence show that XX/XY systems found in two Eupsophus species (Amphibia-Leptodactylidae) represent early stages of sex chromosome differentiation. Pair 14 is heteromorphic in E. migueli males and represents the heterochromosomes. In E. roseus this pair is metacentric and does not show heteromorphism. Paracentromeric constitutive heterochromatin is present in all chromosomes except in the E. migueli and E. roseus metacentric Y chromosomes. Constitutive heterochromatin loss is the structural modification responsible for Y chromosome differentiation. Pericentric inversions may have modified the morphology of the X chromosome of Eupsophus species.Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de ChileDepartamento de Biología Celular y Genética, Facultad de Medicina, Universidad de Chile     

Further evidence for early sex chromosome differentiation of anuran species

Chromosome banding and meiotic evidence show that XX/XY systems found in two Eupsophus species (Amphibia-Leptodactylidae) represent early stages of sex chromosome differentiation. Pair 14 is heteromorphic in E. migueli males and represents the heterochromosomes. In E. roseus this pair is metacentric and does not show heteromorphism. Paracentromeric constitutive heterochromatin is present in all chromosomes except in the E. migueli and E. roseus metacentric Y chromosomes. Constitutive heterochromatin loss is the structural modification responsible for Y chromosome differentiation. Pericentric inversions may have modified the morphology of the X chromosome of Eupsophus species.     

Reserpine effects on neurotransmitters in chick heart during growth

Effects of tranquilizing agents on neurotransmitters in the heart have not been widely studied. Thus, the effect of intraperitoneal injection of reserpine, (2.5 mg/kg bw) on the concentrations of excitatory (glutamic acid, glutamine, aspartic acid, asparagine), inhibitory (GABA, glycine, alanine, taurine), neurotransmitters as well as the enzymes (GOT and GPT) and total protein were measured in both heart and serum of chicks at different ages (1, 7, 30, 90 and 180 days). Reserpine induced a decrease in the excitatory amino acids and an increase in GABA in both heart and serum in most ages. Glycine and alanine increased in the heart and decreased in serum. Taurine increased in the heart of young ages (1 and 7 days) and decreased in older ones (90 and 180 days), however, it decreased in serum of most ages. Both GOT and GPT increased in heart but, in serum, GOT increased and GPT decreased in most ages. Total protein increased in the heart of young chicks and decreased in the 90- and 180-day-old chicks. In conclusion, reserpine induced a parallel decrease in the ratio glutamate, glutamine, aspartate/GABA in both myocardial tissue and serum of the different age groups. Changes observed in neurotransmitters of the heart suggest that these amino acids may play a similar role in the myocardial tissue, as is described in the central nervous system.     

Further evidence for non-pancreatic insulin immunoreactivity in guinea pig brain

The existence of large amounts of insulin in rat brain and of a porcine- or rat-like insulin in guinea pig brain have been disputed on the basis of differing results from standard (Method I) and hydrophobic adsorption techniques (Method II) for concentrating insulin from acid ethanol extracts. To try to resolve these differences, acid ethanol extracts of rat and guinea pig brains were divided into equal aliquots and concentrated for insulin radioimmunoassay (RIA) by both techniques. The RIA used guinea pig anti-porcine insulin serum, with 50% B0 for purified pancreatic porcine, rat and guinea pig insulin standards being 1.35, 2.38 and greater than 1,000 ng/ml, respectively. Oral glucose (4 g/kg) produced plasma glucose of 377 mg/dl in a guinea pig by 20 min but was not associated with any porcine- or rat-like immunoreactive insulin. Dilutions of guinea pig and rat brain extracts had parallel cross-reactivity with insulin standard curves. Insulin contents of rat brain (uncorrected for recovery) against porcine and rat insulin standards, respectively, were 1.33 and 1.93 ng/g (Method I) and 5.93 and 11.67 ng/g (Method II). Rat plasma was 0.85 and 1.42 ng/ml, respectively. Guinea pig contained 1.35 and 1.89 ng/g (uncorrected), respectively (Method I), and 2.99 and 5.62 ng/g, respectively (Method II). Guinea pig plasma was below the sensitivity of the RIA (less than 0.15 ng/ml). These results suggest that a porcine- or rat-like insulin may exist in guinea pig brain.     

Further evidence for Darwin's pangenesis.

Darwin's pangenesis, a developmental theory of heredity, has been largely thought to be wrong for more than a century. In this paper, further evidence for the inheritance of acquired characters and graft hybridization is provided. A striking similarity between mRNA and Darwin's so-called gemmule has been found by comparing their nature and function. I propose that once the term gemmule has been replaced by mRNA, Darwin's pangenesis will revive, indicating an important step in biology.     

Prenatal ethanol exposure in mice: teratogenic effects.

C57BL/6J mice were fed a liquid diet in which 17, 25, or 30% of the calories were derived from ethanol from the fifth through the tenth day of gestation. Control mice were fed lab chow or pair-fed identical diets, except that sucrose substituted isocalorically for ethanol. At term the fetuses were removed and, following fixation, examined by microdissection. The incidence of fetal resorptions and congenital malformations increased in a dose-related manner. Anomalies included skeletal, neurological, urogenital, and cardiovascular systems. These data indicate that in mice, an alcohol diet which is adequate in vitamins and protein results in increased fetal wastage and birth defects.     

Valproic acid-induced placental and teratogenic effects in rats.

Studies on teratogenicity and pathology of the cenceptus were conducted in Sprague-Dawley rats treated with 600, 800, and 1,000 mg/kg valproic acid po on day 13 of pregnancy. Each of the three doses was maternotoxic and caused (1) resorptions and/or abortions, reduction in the number of live fetuses per litter and mean fetal weight, and defects of the tail, rib and phalanx; and (2) degenerative changes in the labyrinth (thrombosis, angiectasis in the maternal lacunar network, necrosis of cytotrophoblasts and suppressed proliferation of fetal capillaries), reduced diameter nearing obliteration of umbilical vessels, with or without karyorrhexis of embryonic tissues. The lesions in the placental labyrinth were specific but, in the embryonic tissues, they were generalized. It was postulated that the vascular lesions in the labyrinth and umbilicus may have influenced embryonic development by reducing maternoembryonic gaseous and nutritional exchange.