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Biomedical subjects

S Zamenhof

Publications and source records attributed to S Zamenhof.

At least 19 recordsLinked to original sources

Neonatal brain parameters: outstanding tails of normal distribution.

Previous studies were concerned with distribution curves of values of brain parameters (weight, DNA or cell number, and protein) in a population of 720 neonatal rats. These values followed normal distribution curves, and the tails of such curves, with values in excess of two standard deviations (SD) above (right hand) or below (left hand) the mean (X), were statistically significant. In the present work a larger sample (1,948) of neonatal rats, with particular reference to those whose brain parameters exceeded three SD above or below X, respectively, was examined. Such occurrences are rare; they are somewhat skewed with respect to numbers expected in the tails of a normal distribution curve. For DNA the highest deviations from X were for 'maximal' brain, +3.62 SD (right tail); and for 'minimal' brain, -4.33 SD (left tail). Further study suggested that one of the factors increasing the maximal values might be a lower number in the litter, and one of the factors decreasing the minimal values was a lower maternal weight at conception. Thus the factors affecting maximal and minimal brains are not the same. The occurrence of such individuals with maximal or minimal values of neonatal brain parameters is of particular interest if these parameters are correlated with behavioural performance.

Animals

Quantitative studies of mitoses: hippocampus of neonatal rat.

In continuation of our quantitative studies of mitoses in 15-day fetal rat brain, we have now studied mitoses in hippocampus of neonatal rat. In contrast to cortex in which neuroblast mitoses terminate prenatally, hippocampus in rodents has been known to exhibit mitoses well past birth. Our present study suggests that at birth (rat) 61% of these mitoses are situated in the medioventral tip of the germinal (ventricular and sub-ventricular) zone of lateral ventricle. However, the remaining 39% of mitoses may not be neural but represent mitoses of brain capillaries, similar to "deep mitoses" which we reported in 15-day fetuses. Like these, some of the neonatal mitoses are situated not in the germinal layer of the ventricle, but 44 +/- 21 microns deeper, near Ammon's horn or dentate gyrus; also, as in these previous studies, the spindles of all deep mitoses are not parallel to ventricular or hippocampal structures but perpendicular, presumably to promote their radial expansion known for capillaries at that age. Possibilities are considered that capillary cells are produced in excess and eventually undergo natural "capillary death", to follow natural "neuronal death".

Animals

Differential effects of chronic ingestion of tritiated water on prenatal brain development.

Female rats were given tritiated drinking water (3 microCi/ml) from 30 days before mating up to and throughout pregnancy. At this low dose, the course and the outcome of pregnancy were normal. The differences between newborn body and cerebral weights of the treated rats and those of control animals were on the borderline of significance. In contrast, cerebral DNA and cerebral protein were highly significantly lower. In 30-35% of the treated population the DNA and protein values were more than 2 standard deviations (SD) below the mean values for the control population. Thus the number of the progeny of the mothers exposed to tritiated water that were considered to have "outstandingly low" levels of DNA and protein was 14-17 times greater than in the control group. The irradiated population also had 3-5% of severely affected individuals with cerebral DNA and protein values more than 2 SD below the mean of the experimental population. However, even in this irradiated population, a certain number of individuals did not show the effects of radiation as indicated by DNA and protein values that were not lower than the mean values of the control population. These animals may represent those individuals in which normal (control) populations would have cerebral DNA and protein levels well above the average (by 1 to 2 SD), but here, because of prenatal irradiation, were about average. If so, this lack of effect of irradiation cannot be caused by protection against radiation. However, at present, a differential repair mechanism of protection in those animals (or their mothers) that showed little or no effect of irradiation cannot be excluded.

Animals

Selective sensitive period in chick embryo: toxic effect of exogenous neurotransmitters.

The phenomenon of sudden mortality in the chick embryo, induced by the exogenous neurotransmitters norepinephrine, epinephrine, dopamine, serotonin, carbachol, and by the beta-blockers propranolol and atenolol, is described. When introduced singly into eggs (albumen) in doses of 0.1 mg per egg, these substances induced highly significant, sharply increased mortality (60% to 100%) when the introduction was on embryonic (incubation) days 8 to 12 (hereafter called E8 and E12), but none if introduction was earlier. These ages follow the appearance of functional receptors (or receptor-effectors) for these substances. However, the involvement of receptors here has not been proved. Solvent alone (Ringer's solution for chick) had no effect, indicating that the procedures used were in themselves not lethal. Possibly, the above neurotransmitters became lethal to the embryo because they were introduced in excess of the amounts which were produced and needed at that time by the embryo for optimal development.

Adrenergic beta-Antagonists

Toxic effects of phencyclidine on developing chick embryo brain.

We studied the effects of Phencyclidine (PCP, Angel Dust) on the developing chick embryo brain. In Group-1, the eggs were injected with PCP on the 7th day of incubation and the embryo brains were studied on the 10th day. In Group-2, eggs were injected twice; first on the 7th day and then on the 10th day of incubation. Group-2 brains were then studied on the 16th day of incubation. PCP significantly depressed the development of embryo brains. Cerebral hemisphere weight, total protein and total DNA were significantly lower on day 10 of incubation in Group-1. Similar results were observed in Group-2. Concomitantly, the concentration of brain serotonin at day 10 was also significantly reduced when PCP was injected into the eggs on the 7th day of incubation. Since serotonin has been reported to influence development of the chick embryo brain, the present finding of the effect of PCP on brain development might be a secondary phenomenon. The possible implications of the effects of PCP on human brain development are also discussed.

Animals

Quantitative studies of mitoses in fetal rat brain: orientations of the spindles.

In continuation of our quantitative studies on 15-day fetal rat brain development, evidence was obtained of ventricular mitoses whose spindles are perpendicular to the surface of the ventricle. In most locations the proportion (ratio) between cells with perpendicular mitoses and predominant cells with mitoses parallel to ventricle is only 0.064 (+/- 0.057): 1; however, in two specific locations of lamina terminalis this proportion is much higher: 2.006 (+/- 1.24): 1 and 0.634 (+/- 0.42): 1. Total mitotic counts in these two locations were also higher: 1.8 and 1.5 X higher than the average elsewhere in cerebral hemispheres. It is suggested that these perpendicular orientations are not accidental but serve some specific purpose: either they give rise to a different cell population, or they represent a stage preparatory for cell migration.

Animals

Effect of intrauterine positions on fetal brain development in the rat.

The effect of the position on the horn on fetal brain development was studied in 2276 rats (248 litters), by assessing the intrauterine location of those fetuses which had the highest values ('maximal fetuses') of the following parameters: body weight, brain weight, brain DNA (cell number), brain protein and the ratios brain weight/body weight and brain protein/brain DNA. The fetuses were at term (21 days) or at 16-18 days postcoitum. The total numbers of animals in the right and in the left uterine horn were essentially the same: 4.64 and 4.54, respectively. For each parameter, the locations of maximal fetuses were, on the average, symmetrical with respect to the center of each horn. The distributions of maximal fetuses along each horn followed specific patterns, which were different for each horn but showed similar locations of peaks and depressions for various parameters. However, the differences between the peaks and depressions were not statistically significant. It is concluded that both horns are equipotent, and all the positions on the horn are also essentially equipotent for production of animals maximal with respect to parameters studied. This also suggests that occasional cases of outstanding high fetal brain development occur from causes other than a favorable position on the uterine horn.

Animals

Quantitative studies of mitoses in cerebral hemispheres of fetal rats.

In continuation of our study of 15-day fetal rat brain development, evidence was obtained of a single layer of mitoses, situated away from the ventricle at a mean depth of 75% of the thickness of the cell layer of cerebral hemispheres ('deep mitoses'). Their number is 17.9% of ventricular mitoses and their spindles are perpendicular to spindles of ventricular mitoses. Their distribution is not correlated with distribution of ventricular mitoses. The fate and destination of these deep mitotic cells is at present unknown; the possibility that they are mitoses of the capillaries has been discussed.

Animals

Differential effects of antifolate on the development of brain parts in chick embryos.

A quantitative study was made of the differential effects of the antifolate amethopterin (methotrexate) on the development of cerebral hemispheres, optic lobes and cerebellum in chick embryos. Most surviving embryos show a significant under-development at day 18 of incubation. Different brain parts respond differently (disproportionately) to the treatment: cerebellum--most drastically, optic lobes--least drastically (net weights). Within the cerebellum, Purkinje and other large cells respond less drastically than small cells. The embryo thus had highly significantly changed ratios of weights of various brain parts and of numbers of various cerebellar cells. Several mechanisms to explain these differential effects have been discussed.

Animals

The effect of progesterone on fetal and placental development in normal and protein-energy-restricted rats.

Maternal protein-energy restriction (25% of the ad libitum intake) during the first 10 days of pregnancy resulted in severely altered fetal growth rates. Fetal development was assessed by body weight, brain weight, brain DNA, and brain protein content on fetal days 16, 18, 20 and at term. The individual placentas were also examined (weight, DNA and protein content) on each of these fetal days. Progesterone was administered commencing with day 3 of pregnancy until the day Caesarian section was done, in an attempt to rehabilitate placental development. This treatment did not improve placental development on fetal days 16 or 18. However, fetal development was significantly improved on day 16 and day 20, as compared to the dietary-restricted group without progesterone.

Animals

Correlations between neonatal body weight and adolescent brain development in rats.

Correlations between neonatal body weight, and body weight and several brain parameters at 30 days of age were studied in normal rats. At 30 days ('adolescence') cortex has already reached its final thickness and the rat exhibits long-term memory. Brain parameters included cerebral weight, DNA, protein and cholesterol contents and densities, as well as cortical and cerebral dimensions (cerebral sections). As expected, most of these parameters in 30-day-old animals were significantly correlated with each other. Unexpectedly, neonatal body weight was also significantly correlated with cholesterol content and density at 30 days, as well as with cortical and cerebral dimensions at 30 days. Thus, statistically, neonatal body weight already predetermines the extent of neuronal (cerebral) development at adolescence (30 days). This finding also makes it possible to make at birth statistical predictions about future brain development without having to sacrifice neonatal animals.

Animals

The effect of progesterone on brain and body growth of chick embryos.

It has been suggested that in the embryo hormonal steroids may act also as control factors for the growth of neural systems. In the present work progesterone was introduced onto the chorioallantoic membrane of the chick embryo on day 7 or days 7 and 10 of incubation. The embryo, dissected at day 10, showed significant increases in body weight and cerebral hemispheres weight. The response at day 13 was less pronounced; male embryos responded to progesterone more than the female embryos. Progesterone is a precursor to other corticosteroids, but corticosterone itself had a significant harmful effect on embryonal growth. Several possible explanations of these results have been offered. It appears that progesterone itself promotes the growth of the early embryo, but the effect depends on its age and sex.

Animals

The effects of exogenous nutrients on growth of chick embryo brain.

The effect of an early addition of exogenous nutrients on brain growth has been investigated in chick embryo. The nutrients were introduced onto chorioallantoic membrane at day 6 or 7 of embryonal life, and the cerebral hemispheres examined at the end of neuronal proliferation for the following parameters: weight, DNA content (index of cell number) and protein content. L-Tryptophan produced significant inhibition, probably by creating amino acid imbalance and interference with the transport of other amino acids. D-Tryptophan (slower transport) was inactive. 5-Methyltryptophan produced significant inhibition, probably by causing deficiency of tryptophan utilization and of production of serotonin, which is a growth factor for early brain. Glycine stimulated brain growth, probably by conversion to glucose which is the main energy source for the embryo in this period. Brain weight and DNA were found to be significantly correlated with blood glucose level. It is concluded that, within genetic limits, early brain growth might be manipulated in both directions (inhibition or stimulation) by addition of proper nutrients during sensitive period of neuronal proliferation.

Age Factors

The effects of chronic undernutrition over generations on rat development.

Experimental rats were fed 2/3 (10g/24 hours) of adlibitum diet throughout pregnancy and post-weaning, thus far for six generations; their brain and body development was compared with those of controls fed ad libitum (15.5 g/24 hours). As expected from previous reports, neonatal F1 offspring exhibited highly significant decreases in body weight, cerebral wet weight, cerebral DNA and cerebral protein. However, neonatal decreases were not greater in F2 through F6 than in F1 indicating that there was no cumulative effect of this undernutrition on offspring's parameters over generations. Maternal body weight at mating (90 days) and percentage of females that did not litter steadily decreased over generations. The observed high mortality in F1 through F6 and the resulting strong natural selection in favor of best mothers and weanlings could explain these findings. The phenomena contributing to high mortality are multiple and involve maternal factors during pregnancy and before weaning, as well as offspring factors.

Aging