Environmental enrichment and the brain.
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Aging↗
Biomedical subjects
M C Diamond
Publications and source records attributed to M C Diamond.
Mental stimulation increases circulating CD4-positive T lymphocytes: a preliminary study.
To stimulate the dorsolateral frontal cortex, 12 healthy, adult, human females played contract bridge for 1.5 h between initial and final blood sample collections. Flow cytometric analyses of samples, performed in triplicate, showed a significant increase in CD4-positive T lymphocytes. The dorsolateral frontal cortical thickness is significantly and bilaterally reduced in immune-incompetent female, nude mice. Thymic transplants reverse the deficient cortical thickness and CD4-positive cell numbers.
Aged↗
Response of the brain to enrichment.
Before 1960, the brain was considered by scientists to be immutable, subject only to genetic control. In the early sixties, however, investigators were seriously speculating that environmental influences might be capable of altering brain structure. By 1964, two research laboratories proved that the morphology and chemistry or physiology of the brain could be experientially altered (Bennett et al. 1964, Hubel and Wiesel 1965). Since then, the capacity of the brain to respond to environmental input, specifically "enrichment," has become an accepted fact among neuroscientists, educators and others. In fact, the demonstration that environmental enrichment can modify structural components of the rat brain at any age altered prevailing presumptions about the brain's plasticity (Diamond et al. 1964, Diamond 1988). The cerebral cortex, the area associated with higher cognitive processing, is more receptive than other parts of the brain to environmental enrichment. The message is clear: Although the brain possesses a relatively constant macro structural organization, the ever-changing cerebral cortex, with its complex microarchitecture of unknown potential, is powerfully shaped by experiences before birth, during youth and, in fact, throughout life. It is essential to note that enrichment effects on the brain have consequences on behavior. Parents, educators, policy makers, and individuals can all benefit from such knowledge.
Adaptation, Physiological↗
Effects of methyltestosterone on insulin secretion and sensitivity in women.
The frequent coexistence of hyperandrogenism and insulin resistance is well established; however, whether a cause and effect relationship exists remains to be established. In this study we tested the hypothesis that short-term androgen administered to women would induce insulin resistance. To test this hypothesis, regularly menstruating, nonobese women were studied before and during methyltestosterone administration (5 mg tid for 10-12 days) by the hyperglycemic (n=8) and euglycemic, hyperinsulinemic (n=7) clamp techniques. Short-term methyltestosterone administration had no significant effects on the fasting levels of glucose, insulin, c-peptide, glucagon, or glucose turnover. During the hyperglycemic clamp studies, the mean glucose level during the final hour was 203+/-2 and 201+/-1 mg/dL in the methyltestosterone and control studies, respectively. The insulin response to this hyperglycemic challenge was slightly but not significantly greater during methyltestosterone treatment (first phase 59+/-8 vs. 50+/-8 microU/mL in controls; second phase 74+/-9 vs. 67+/-9 microU/mL in controls; total insulin response 133+/-16 vs. 117+/-15 microU/mL in controls). In spite of this, glucose uptake was reduced from the control study value of 10.96+/-1.11 to 7.3+/-0.70 mg/kg/min by methyltestosterone (P < 0.05). The ratio of glucose uptake per unit of insulin was also significantly reduced from a control study value of 14.3+/-1.4 to 9.4+/-1.3 mg/kg/min per microU/mL x 100 during methyltestosterone administration. In the euglycemic hyperinsulinemic clamp studies, insulin was infused at rates of 0.25 and 1.0 mU/kg/min to achieve insulin levels of approximately 25 and 68 microU/mL, respectively. During low-dose insulin infusion, rates of endogenous hepatic glucose production were equivalently suppressed from basal values of 2.37+/-0.29 and 2.40+/-0.27 mg/kg/min to 0.88+/-0.25 and 0.77+/-0.26 mg/kg/min in the methyltestesterone and control studies respectively. Whole body glucose uptake during low-dose insulin infusion was minimally affected. During the high-dose insulin infusion, endogenous hepatic glucose production was nearly totally suppressed in both groups. However, whole body glucose uptake was reduced from the control value of 6.11+/-0.49 mg/kg/min to 4.93+/-0.44 mg/kg/min during methyltestosterone administration (P < 0.05). Our data demonstrate that androgen excess leads to the development of insulin resistance during both hyperglycemic and euglycemic hyperinsulinemia. These findings provide direct evidence for a relationship between hyperandrogenemia and insulin resistance, and its associated risk factors for cardiovascular disease.
Adult↗
Thymus graft reverses morphological deficits in dorsolateral frontal cortex of congenitally athymic nude mice.
The present investigation offers a basis for demonstrating that the cerebral cortex can be directly accessed through the immune system. This project was undertaken to provide a necessary step in confirming that the localized, deficient area of the cerebral cortex in the congenitally athymic nude mouse is related to the thymus, a gland necessary for the development of T-cells and the regulation of the neuro-endocrine system. We report that thymus engraftment, confirmed by reconstitution of CD4 and CD8 T-cells, in 30-day-old congenitally athymic female mice reverses deficiencies in the frontal cortex by day 60. A concomitant increase in serum prolactin was observed in thymic-grafted nude mice, suggesting a role by which prolactin may produce the morphological changes observed in the cerebral cortex.
Animals↗
Prolactin increases CD4/CD8 cell ratio in thymus-grafted congenitally athymic nude mice.
One distinctive effect on T-cell development was analyzed by selectively increasing serum prolactin (PRL) concentration in thymus-grafted congenitally athymic nude mice and by neutralizing PRL in suspension cultures of thymus from 1-day-old neonatal mice. Flow cytometric analysis of single-positive CD4+ and CD8+ cells derived from inguinal lymph nodes revealed a CD4/CD8 cell ratio of 2.2 +/- 0.18 (mean +/- SEM) in thymus-grafted nude mice that is similar to the ratio for immune-competent BALB/c mice (2.0 +/- 0.06). Addition of the pituitary to thymus-grafted nude mice significantly elevated serum PRL (P < 0.005) and increased the CD4/CD8 cell ratio (2.8 +/- 0.12; P < 0.005), demonstrating preferential stimulation of CD4+ cell development. T cells in nude mice receiving sham (submandibular salivary gland) or pituitary grafts alone were below detectable levels. Suspension cultures of neonatal thymus treated with anti-mouse PRL antiserum resulted in 20% and 30% decreases in double-positive CD4+8+ thymocytes and thymocyte viability, respectively. A 10-fold increase in double-negative CD4-8- thymocytes expressing the interleukin 2 receptor alpha chain, CD25, was also observed concurrently. Our findings illustrate an important way in which PRL may participate in two interrelated mechanisms: the regulation of peripheral single-positive cells and the maintenance of thymocyte viability during the double-positive stage of intrathymic differentiation.
Analysis of Variance↗
Chemical and anatomical plasticity of brain. 1964.
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Animals↗
Gender influences counterregulatory hormone responses to hypoglycemia.
It has been generally assumed that counterregulatory hormone responses to hypoglycemia are not influenced by gender. To test this assumption, we analyzed three separate hypoglycemic insulin clamp studies in age-matched, healthy, non-obese females (n = 33) and males (n = 37). In one study (12 females, 17 males), plasma glucose level was rapidly decreased to about 57 mg/dL for 100 minutes with a 0.65-mU/kg/min insulin infusion. Despite an identical decrease in glucose level, the increase in epinephrine (361 +/- 64 v 188 +/- 38 pg/mL, P < .05), norepinephrine (132 +/- 28 v 47 +/- 19 pg/mL, P < .01), and growth hormone ([GH] 16.0 +/- 3.8 v 4.9 +/- 1.9 ng/mL, P < .05) levels, but not glucagon or cortisol levels, were significantly greater in males than in females, respectively. In the second study (10 females, eight males), a 5.0-mU/kg/min insulin infusion was used to decrease glucose levels to 55 mg/dL for 180 minutes. Epinephrine (P < .05) and GH (P < .01) responses were greater in males than in females. In a third study (11 females, 12 males), plasma glucose level was gradually decreased to about 50 mg/dL over 240 minutes. Again epinephrine (P < .01), norepinephrine (P < .01), GH (P < .05), and cortisol (P < .01) responses were nearly twofold greater in males (P < .01). Multivariate analysis of all 70 subjects identified gender as the most significant factor contributing to the epinephrine (P < .001) and norepinephrine (P < .005) responses, and also as a significant contributor to the GH response (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hormonal effects on the development or cerebral lateralization.
The morphology of cerebral cortical laterality patterns differs between the sexes. In the male Long-Evans rat, the thickness of the cerebral cortex is, in general, greater on the right side than on the left, with many areas showing statistically significant differences. In the female Long-Evans rat, the left side is thicker more often than the right, but the differences, in general, are not statistically significant. These laterality patterns are maintained throughout the lifetime of the animal with few variations. Some of the male and female laterality patterns reverse with old age. The numbers of neurons and glial cells in the area sampled, area 39, support the direction of cortical thickness measurements in male and female rats. Removal of the testes or ovaries at birth alters the usual cortical laterality patterns, illustrating that the sex steroid hormones play some role in determining laterality. In the neonates of both sexes, estrogen receptors are found in the cerebral cortex, but the concentration is greater in the left male cortex than in the right, the opposite being true for the female. Factors other than the sex steroid hormones, such as stress, can alter cortical laterality. Many studies indicate that plasticity of laterality is a factor to be considered when dealing with cortical morphology and, in turn, behavior.
Animals↗
Sex and the cerebral cortex.
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Cerebral Cortex↗
Effect of environmental enrichment during nutritional rehabilitation on body growth, blood parameters and cerebral cortical development of rats.
Environmental enrichment has been reported to aid recovery from behavioral deficits associated with malnutrition in infants and young rats. This study investigated whether corresponding neuroanatomical changes could be detected. Rats were suckled either by well-fed dams or dams malnourished during lactation. At weaning, well-fed males were either housed in pairs (standard condition, SC) or 12 per large cage with toys (enriched condition, EC) and fed a 17% protein diet (SC control and EC control, respectively). Malnourished pups were fed either a 17% (rehabilitation; "rehab") or a 6% (low protein) protein diet and housed in the SC or EC environment (SC rehab, EC rehab, SC low protein, and EC low protein). After 30 d there were no differences in hematocrit, serum total protein and albumin levels between SC and EC animals. Rehab rats had significantly lower serum total protein and albumin levels than did controls. Cortical thickness and dendritic branching of occipital cortex pyramidal cells were evaluated. Early malnutrition did not permanently affect cortical thickness. EC rehab rats had thicker cortices than did SC rehab rats at almost all locations measured. SC rehab rats had fewer high order dendrites than did SC controls. The difference in dendritic branching between EC and SC rats was 44% among rehab rats, 21% among controls and 11% (not significant) among low protein-fed rats. Environmental enrichment during nutritional rehabilitation enhances dendritic branching and thickness of the occipital cortex.
Animals↗
Cortical asymmetry--a preliminary study: neurons-glia, female-male.
Previous studies on human cortical area 39 suggested that neuron:glial ratios differed between the sexes. These findings were the inspiration for the present investigation which dealt with neuronal and glial counts in area 39 in the male and female rat cerebral cortex. Transverse, celloidin or frozen sections, were cut from male and female brains (respectively) from 90-day-old Long-Evans rats. Neurons and glia were counted on enlarged photographs of stained sections, including area 39, with 35-mm Kodak Panatomic-X film using a Zeiss photomicroscope (X400). Five-by-three-inch prints were taped together in sequence to yield a 640X enlarged "montage" of area 39. Five cell types were differentiated with reference to a standard: neurons, astrocytes, oligodendrocytes, "dark astrocytes," and unidentified glia. The data were analyzed with a two-way analysis of variance (ANOVA: five cell types by two hemispheres). Student's t test and a paired t test were used when appropriate. The neuron:glial ratios in the male rats were consistently higher than those in the females in both hemispheres. The male right side had 12% (P less than 0.05) more neurons than the left; the female had 13% (P less than 0.05) more neurons on the left than the right. Similar, but not identical, asymmetrical patterns were seen with the glial cells.
Animals↗
Rat cortical morphology following crowded-enriched living conditions.
This experiment studied cerebral cortical morphology in rats living in a crowded-enriched condition. Three groups of 60-day-old, male Long-Evans rats were divided accordingly: 12 rats, 3 per small cage (32 X 20 X 20 cm), standard colony condition; 12 rats in a single, large, enrichment cage with "toys" (70 X 70 X 45 cm), enriched condition; and 36 rats in a large, single, enrichment cage with "toys", crowded-enriched condition. Matched toys for the two enriched cages were changed twice a week at the time of cage cleaning. Measurements on 20-micron, transverse brain sections showed that in both the crowded-enriched and enriched groups the thickness of the medial occipital cortex increased by 4 to 6% compared with the cortex from animals in the standard colony condition. In addition, the crowded-enriched group demonstrated a 4% (P less than 0.05) increase in thickness in area 39 in the left hemisphere compared with the standard control. However, the thickness in area 39 in the crowded group was not significantly different from that of the enriched area 39. These results indicate that the cortex increases in thickness as much with "crowding" and enrichment as with enrichment alone. We hypothesize that diversion through interaction with "toys" mitigates the stress of crowded conditions.
Animals↗
Sex differences in the rat forebrain.
In the first postnatal month, the thickness of the cerebral cortex has different patterns of development in the male and female Long-Evans rat. All areas of the male cortex appear to develop at similar rates, very rapidly for the first 10 days, then more gradually reaching a peak somewhere between 30 and 40 days of age before beginning to decrease in thickness. The same is not true for the female; for example, at birth her medial frontal cortex is further developed than her lateral posterior parietal cortex and the rate of growth in the first weeks varies immensely. The male right cortex is thicker than the left from birth to 904 days of age, but the differences become less significant with age. The female cortex is thicker on the left side in the majority of the cases, from 7 to 400 days of age, but the differences are not in general statistically significant. Estrogen receptors are found in both male and female rat cerebral cortices at birth and apparently disappear after one month. In the male the greatest concentration of receptors is in the left cortex, and in the female, in the right. The number of neurons and glia per unit area is greater in the right cortex (area 39) in the male; and in the female, in the left cortex. Ninety days after ovariectomy at birth, the female right cortex is thicker than her left, establishing a pattern similar to that of the male. In the male gonadectomized at birth, the left cortex is thicker 90 days later in the frontal and somatosensory regions but not in the occipital or posterior region.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regional cerebral cortical deficits in the immune-deficient nude mouse: a preliminary study.
This report examines the morphology of the cerebral cortex in the nude mouse (nu/nu) compared with the BALB/c(+/+). Our experiments indicated that the thickness of the lateral frontal lobe was significantly reduced (8%; P less than 0.005) in the 4-month-old, female nude mouse compared with a BALB/c mouse of like sex and age. In addition, the left hemisphere was, in general, thinner in the nude than in the BALB/c, with area 18 being significantly thinner (2%; P less than 0.005). Oligodendrocytes were less in area 18 in the nude by 25% (P less than 0.02) in contrast to the BALB/c. In some respects these results extend the work of others. In previously published experiments, we showed that the thickness of the frontal cortex from enriched and impoverished female rats (from 60 to 116 days of age) differed by 2 to 3% (P less than 0.001) and in male rats by 3 to 4% (P less than 0.001). The oligodendrocytes in area 18 in the male differed by 20% (P less than 0.02) in rats exposed to their respective enriched or impoverished environments from 25 to 105 days of age. Thus, we have shown that the frontal cortical morphology as well as the occipital cortical oligodendrocytes were altered in both immune-deficient animals and environmentally stimulated or impoverished animals. Based on these separate sets of data, we will be interested to learn if our environmental conditions can alter the immune system and if so by what mechanism.
Animals↗
Rat cerebral cortical estrogen receptors: male-female, right-left.
We determined the concentration of cytosol estrogen receptors in the postnatal, developing right and left cerebral cortices of Long-Evans male or female rats 2 to 3, 7 to 8, 14 to 15, and 25 to 26 days of age. Under anesthesia, the rats were gonadectomized and 24 h later they were killed by decapitation, and the dorsal right and left cerebral cortices were separated from the underlying white matter and placed on ice. Sephadex LH-20 gel filtration chromatography was used to dissociate the majority of alpha-fetoprotein-bound [3H]estradiol while leaving the receptor [3H]estradiol complex intact. The correction for the residual nonreceptor binding, including alpha-fetoprotein, was made using parallel incubation containing unlabeled diethylstilbesterol. The amount of residual nonreceptor binding was subtracted from [3H]estradiol-bound protein to calculate high-affinity estradiol binding receptors. The results showed that in both sexes, estrogen receptor concentration was highest at postnatal days 2 to 3 in both the right and the left cerebral cortex and then decreased until 25 days of age. In the female, the right cerebral cortex, at postnatal day 2 to 3, had a higher estrogen receptor concentration than the left cortex (P less than 0.02). In the male, the left cortex had a higher cytoplasmic estrogen receptor concentration (P less than 0.02) than the right. Considering the reported growth-inhibiting effects of estrogen on the cerebral cortex, the results indicated that one determinant of cerebral dominance in both sexes may be the differential exposure to estrogen, in the case of the male testosterone converted to estrogen, during a critical period of development.
Animals↗
Neuroscience in China.
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Acupuncture Therapy↗
On the brain of a scientist: Albert Einstein.
Neuron:glial ratios were determined in specific regions of Albert Einstein's cerebral cortex to compare with samples from 11 human male cortices. Cell counts were made on either 6- or 20-micron sections from areas 9 and 39 from each hemisphere. All sections were stained with the Klüver-Barrera stain to differentiate neurons from glia, both astrocytes and oligodendrocytes. Cell counts were made under oil immersion from the crown of the gyrus to the white matter by following a red line drawn on the coverslip. The average number of neurons and glial cells was determined per microscopic field. The results of the analysis suggest that in left area 39, the neuronal: glial ratio for the Einstein brain is significantly smaller than the mean for the control population (t = 2.62, df 9, p less than 0.05, two-tailed). Einstein's brain did not differ significantly in the neuronal:glial ratio from the controls in any of the other three areas studied.
Aged↗