Biomedical subjects

V H Denenberg

Publications and source records attributed to V H Denenberg.

At least 73 records · Page 4Linked to original sources

PubMed1991

Effects of the autoimmune uterine/maternal environment upon cortical ectopias, behavior and autoimmunity.

NZB and BXSB mice develop autoimmune disease and learn poorly on avoidance tasks. In addition, many of these mice have ectopic collections of neurons, which occur prenatally, in layer I of the cerebral neocortex. The purpose of these experiments was to evaluate the contribution of the uterine/maternal environment upon these variables by transferring fertilized ova to an autoimmune or a non-autoimmune maternal host. In Experiment 1 fertilized DBA ova were transferred into the uteri of BXSB maternal recipients. Later, these animals and conventionally reared DBAs were tested for paw preference, swimming rotation, water escape learning, and shuttlebox avoidance learning. Blood was taken for measurement of immune parameters, and their brains were examined for cortical ectopias. As compared to conventional DBAs, the ova transfer mice had greater amounts of anti-dsDNA autoantibodies, poorer avoidance learning, and poorer water escape learning; in addition, the females had greater paw asymmetry. There was only 1 ectopia in the 81 ova transfer animals, and none in the 78 control mice. In Experiment 2 fertilized NZB ova were transferred into the uteri of non-autoimmune hybrid females and the same procedures were followed as in Experiment 1. Ova transfer mice had lesser amounts of anti-dsDNA autoantibodies, better avoidance learning scores, and females had less paw asymmetry; in addition, within the ova transfer group males were clockwise swimmers whereas females swam counterclockwise. There were 4 ectopics out of 17 ova transfer mice (23.5%), which did not differ from the 40.5% of the control group. In both experiments the uterine environment did not affect the occurrence of ectopias.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Spatial learning, discrimination learning, paw preference and neocortical ectopias in two autoimmune strains of mice.

NZB and BXSB mice were given a battery of behavioral tests including paw preference, water escape, Lashley III maze, and discrimination learning. Their brains were then evaluated for cortical ectopias. The incidence of ectopias was 40.5% in NZBs and 48.5% in BXSBs. In the NZB strain left-pawed ectopic mice (both male and female) had the fastest swimming time in the water escape test, while right-pawed ectopics were the slowest. The same findings were obtained for left- and right-pawed ectopic BXSB males, but not for the females. However, on discrimination learning the BXSB males had the exact opposite pattern: right-pawed ectopics were the best learners while left-pawed ectopics were the worst. Male BXSBs and both male and female NZBs were manifesting autoimmune disease at the time of testing, while female BXSBs were not, suggesting that autoimmunity is a necessary background condition for the differential expression of ectopias and paw preference upon learning processes. The finding that the left-pawed ectopic BXSB mice, who were the poorest learners in the non-spatial discrimination learning test, learned best in the spatial water escape test is in agreement with the Geschwind hypothesis that pathological events during brain development may, in some instances, produce superiority of function.

Animals↗

PubMed1991

A factor analysis of the human's corpus callosum.

We have recently developed a computer program for measuring midsagittal sections of the human corpus callosum, similar to one used for the rat. Callosal area, perimeter, axis length, and 99 widths for 104 subjects were entered into a factor analysis in order to define regional clusters. Seven width factors were obtained. Regional widths were found to be sensitive to Sex X Handedness interactions in the anterior body, with right-handed females and left-handed males being larger. In the posterior body males had wider callosa than females. A further analysis within the 'isthmus' region compared consistent and non-consistent right-handed males and females. Consistent right-handed males and both female groups had smaller callosa than non-consistent right-handed males. These findings confirmed the use of consistency of handedness as an important independent variable with respect to human callosal morphology.

Adult↗

PubMed1991

Corpus callosum: ovarian hormones and feminization.

The rat's corpus callosum is sexually dimorphic with the male's being larger. This difference appears to depend in part on the neonatal presence of testosterone in the male and ovarian hormones in the female. To further investigate the possibility that ovarian hormones participate in the differentiation of the rat's callosum, females received one of the following treatments on postnatal day 8, 12 or 16: (1) ovariectomy (Ovx); (2) 1 mg of testosterone propionate (TP); or (3) sham surgery. All animals were handled daily from birth until weaning. They were sacrificed at 110 days and a mid-sagittal section of the callosum was obtained. From this section measures of callosal area, perimeter, length, and 99 widths were derived. Widths were averaged into 7 factors as defined by prior factor analysis. Ovariectomy, whether on day 8, 12 or 16, enlarged callosal area and 3 of the callosal width factors. TP had no effect on any callosal variable when administered on day 8, 12 or 16. A comparison of control males and females replicated our prior findings of sexual dimorphism. We conclude that ovarian hormones act to feminize the female callosum, and that their removal results in defeminization. Furthermore, the fact that ovariectomy was effective as late as day 16, while TP treatment on day 8 or later had no effect, suggests that masculinization and feminization of this structure constitute separate processes with distinct sensitive periods.

Aging↗

PubMed1991

A measure of lateral paw preference in the mouse.

A lateral paw preference testing unit is described. Mice are allowed access to preferred food with either their left or right forepaw, and the amount eaten with each paw is measured. The unit allows easy measurement and quantification of this behavior, without requiring food deprivation or continuous monitoring of the subjects, and may be performed in the subject's home cage. Its reliability under a number of conditions is reported. The results do not correlate with those obtained using the Collins paw preference test.

Animals↗

PubMed1991

A computer-aided procedure for measuring Lashley III maze performance.

As an animal swims through the Lashley III maze, an observer types into a Macintosh computer the path taken. The computer program, Observe Software, then breaks the string of choices into two-step sequences and counts the number of such sequences. These data are then sent to a spreadsheet, where the sequences are sorted into forward and backward responses. Forward choices are Correct Path, T Choice Errors and Cul Entry Errors. All backward choices are errors, by definition. They are classified as T Choices, Cul Entries, Cul Exits, and Return to Start. The animal's behavior is then described by the various error classes plus a measure called Learning Index. Examples of learning by rats and mice are presented.

Animals↗

PubMed1991

Corpus callosum: multiple parameter measurements in rodents and humans.

A magnified drawing of a human or a rodent corpus callosum is traced on a digitizing tablet. From this tracing the computer calculates callosal area, perimeter, length, and 99 widths, one for each percentile location along the longitudinal axis of the callosum. In addition, the human program encloses the callosum within a rectangle to obtain several other measures. The use of percentile widths allows one to generate a callosum profile to compare different clinical groups or different species. The human callosum program is compared to one recently reported by another research group.

Algorithms↗

PubMed1991

Corpus callosum: demasculinization via perinatal anti-androgen.

The male rat's corpus callosum is significantly larger than the female's. This dimorphism depends in part on the early presence of testosterone, since postnatal administration of testosterone to female pups enlarges their callosa in adulthood to the size of males. However, castrating males on day 1 is ineffective in reducing (demasculinizing) the size of their callosa as adults. We then addressed the question as to whether testosterone acts prior to day 1 to enlarge the callosa of males. To investigate this hypothesis pregnant rats were administered a non-steroidal androgen blocker, flutamide, during the last 5 days of pregnancy, while controls received vehicle only. Male pups from flutamide litters were castrated on day 3 to prevent postnatal recovery following clearance of flutamide, while others received sham surgery. Callosal sex differences were found between males and females of control litters, but not between males and females from flutamide litters. The absence of sex effects among flutamide litters was a consequence of small callosal size in flutamide-castrated males as compared to control males. We concluded that the prenatal production of testosterone in the male rat pup contributes to sexual dimorphism in the callosa of adult rats.

Androgen Antagonists↗

PubMed1991

Corpus callosum: interactive effects of infantile handling and testosterone in the rat.

Previous research found that the corpus callosum of male rats is larger than that of females; handling rats in infancy enhances this sex difference; and female rat pups, when handled in infancy and given 1 injection of testosterone propionate (TP) on Day 4 of life, will have callosa as large as those of males. In 2 experiments, male pups were castrated on Day 1 or received sham surgery; female pups were injected with TP on Day 4 or received an oil injection. Litters were handled or nonhandled. The previous finding that females, when handled and given TP in infancy, have a larger callosum was confirmed; however, a TP effect when administered to nonhandled females was not found. Because handling is known to cause a corticosterone release, these findings were interpreted as evidence of a developmental interaction between adrenal and gonadal hormones at the cortical level.

Animals↗

PubMed1990

Corpus callosum: effects of neonatal hormones on sexual dimorphism in the rat.

The rat's corpus callosum is sexually dimorphic, with the male's being larger. In addition, giving rats extra stimulation in infancy via handling increases callosal area in males, but not in females. To determine if this dimorphism is testosterone-dependent, male pups were castrated on Day 1 of life while females received an injection of testosterone propionate (TP) on Day 4. Control males had sham surgery and control females received an injection of sesame oil. All animals were handled daily from birth until weaning. Animals were sacrificed at 110 days and a mid-sagittal section of the callosum was obtained. From this section measures of callosal area, perimeter, length, and 99 widths were derived. We verified our previous finding that the male callosum is larger than that of the female. Neonatal TP treatment masculinized the callosa of the females, but castration did not affect the males. TP treatment affected the width dimension of the callosum but not callosal length or brain weight. In a related study the synthetic estrogen DES did not increase callosal size for castrated males or for intact females, while the estrogen blocker, tamoxifen, had a defeminizing effect on females' callosa. These findings suggest that there is an estrogen-dependent active process of feminization of cortical tissue in the female brain.

Animals↗

PubMed1990

A computer-aided procedure for measuring swim rotation.

As a rat or mouse swims in a small cylinder, its movements are tracked by an observer using a joystick, and the information is sent to a Macintosh computer. The swimming circle is broken into quadrants. The sequence of quadrants entered and the time spent in each quadrant are recorded as the basic data. From the data set one can extract full or partial turns, clockwise or counterclockwise rotations, total activity, and speed of swimming clockwise and counterclockwise. Two laterality indices, one based on full turns and the other on partial turns, are calculated. Test-retest reliability for rats and mice for 3-minute and 5-minute observation intervals are reported.

Animals↗

PubMed1990

A computer-aided procedure for measuring discrimination learning.

A computer program is described for a two-choice black-white T-maze discrimination task involving 10 trials per day for 5 days. A Gellerman series of 44 semirandom L/R sequences is included within the program to specify the location of the reinforcing stimulus on each trial. A picture of the T-maze appears on the screen, and the experimenter tracks the animals's movements as it goes through the maze. At the end of the 10 trials, the following statistical information is obtained: number of initial choices into the left alley, number of correct choices, number of trials in which no choice was made, median time to make a choice, and a learning score based upon the path taken by the animal. These data are then sent to Excel for statistical processing.

Animals↗

PubMed1989

A factor analysis of the rat's corpus callosum.

Previous work from our laboratory (Berrebi et al., Brain Research, 438 (1988) 216-224) demonstrated region-specific sexual dimorphisms in the size of the rat's corpus callosum, which are modifiable by extra stimulation in early life. These differences are assumed to reflect regional corticocortical fibers of passage which are altered differentially by gender and our experimental manipulations. In this paper, we report our findings when the original data are reanalyzed using a newly developed computer program. This program not only reproduced, with very high accuracy, the original means, but also permitted us to examine computer generated callosal width scores via a factor analysis procedure. Such a procedure yields useful information concerning the clustering of callosal fibers and thus contributes significantly to our hypothesis that discrete cortical regions are selectively sensitive to experimental variables. Factor analyses of the callosal variables and brain weight of 155 rats found 7 width factors, and an eighth factor which contained the variables of brain weight, callosal length, and callosal perimeter. Callosal area did not load significantly on any of these factors. The percentile locations of the width factors, starting at the anterior (genu) end were: widths 1-5, 6-17, 24-38, 46-57, 62-72, 79-95 and 96-99. Use of these factor scores in analyses of variance revealed that the male callosum is wider than the female's, with the differences most pronounced in the genu and the most posterior portion of the splenium. Both age and early handling experience influenced the callosal width factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Corpus callosum: region-specific effects of sex, early experience and age.

In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization.

Aging↗

PubMed1987

The sleeping and waking states of infants: correlations across time and person.

Study of the sleeping and waking states of infants was extended to the time domain by analyzing their temporal covariation over a 4-week interval using the intra-person correlation coefficient. As a methodological question, inter-person and intra-person correlation matrices were compared. Twenty-eight fullterm, normal infants were observed in the home weekly from 2 to 5 weeks of age. Over each 7-hour observation, the following states were recorded every 10 seconds: Alert, Non-Alert Waking Activity, Fussing, Crying, Daze, Drowse, Sleep-Wake Transition, Active Sleep, Quiet Sleep, and Unclassified Sleep (sleep during periods of the day when a mother was holding her baby). Data were obtained in two social contexts: when the baby was with the mother and when alone. Significant individual differences were found for each of the states in both social contexts. When the baby was alone, there were a greater number of intra-person correlations than inter-person correlations. All correlations between the waking states and Active Sleep or Quiet Sleep were negative, suggesting the hypothesis that the underlying neurobiological mechanisms may allow a degree of substitution among coupled sleep and wake states. This is an extension of the original hypothesis by Roffwarg, Muzio, and Dement. There were fewer systematic relationships among the states when the babies were with their mother in comparison with periods when they were alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Child Behavior↗

PubMed1986

Callosal mediation of cortical inhibition in the lateralized rat brain.

This paper tested a brain model for muricide. The model states that, in animals given handling stimulation in infancy, the right hemisphere is dominant for the occurrence of mouse killing and the left hemisphere acts to inhibit this behavior. On the assumption that the inhibition is mediated transcortically, it follows that severing the corpus callosum should result in an increase in muricide. This prediction was confirmed. In addition, prior research has found that animals not given extra stimulation in infancy show no evidence of lateralization for muricide. Therefore, splitting the brains of this group should not have any effect. This prediction was also confirmed. Latency analyses of muricidal rats found that those with only an intact right hemisphere killed much more quickly than those with only an intact left hemisphere. Sham controls had killing latencies similar to animals with only a right hemisphere. This pattern represents a brain model in which the right hemisphere is dominant for latency to kill. Rats exposed to mice in early life killed much more quickly than those without this early social experience, thus indicating that familiarity can reduce killing latency.

Aggression↗

PubMed1985

Theophylline affects sleep-wake state development in premature infants.

This study investigated the prolonged effects on state behavior of theophylline administered to infants for apnea of prematurity. There were three groups: Four premature infants who had received theophylline in the preterm period, five premature infants who had not received theophylline, and twenty-eight normal fullterm infants. The Theophylline infants had been off the drug for at least one month prior to the beginning of the study. Sleep-wake states were observed in the home for seven-hour periods when all infants were the same corrected ages: two, three, four and five weeks post-term. Data from the portion of the day that the infants were alone were analysed for this study. The state organization of the Theophylline group differed significantly from those of the other groups. They exhibited more non-alert waking activity, more alert, more drowse or transition, and less active sleep than did the Non-Theophylline and Fullterm infants. The state distributions of the latter two groups did not differ. On the basis of similarities between the results of this study and of a previous animal study, it was concluded that theophylline altered the normal development of state organization in premature infants. These effects persisted long after the drug had cleared the body.

Female↗

PubMed1984

Neonatal tail posture and its relationship to striatal dopamine asymmetry in the rat.

Previous research has demonstrated a link between rotational behavior and striatal dopamine asymmetry in the rat (rats rotate contralateral to the side of higher striatal dopamine concentration) and that the direction of a rat pup's tail posture will predict rotational bias. The present study hypothesized that neonatal tail posture would also predict adult striatal dopamine asymmetry. This hypothesis was confirmed for animals with a left but not right tail posture.

Animals↗