Prolonged exposure to odors in the rat: effects on odor detection and on mitral cells

Rats were raised from four to seventy days of age in ethylacetoacetate(EA), 4-methylvaleric acid (MV), or clean air (CA) vapor. Halfof the animals in each group were sacrificed immediately uponremoval from the exposure cages and the remaining animals werehoused in a vivarium, placed on a water deprivation scheduleand trained to detect EA and MV odors prior to sacrifice. Theonly behavioral deficit observed was in the slower acquisitionof the MV odor detection task for rats which were raised inMV vapor and were tested first on that vapor. Inspection ofselected 10µm thick Nissl-stained sections of olfactorybulbs revealed no differences in intensity of staining, sizeof mitral cells or number of mitral cells between immediatelysacrificed and later sacrificed animals, or among the exposuregroups. These results are in agreement with reports that prolongedexposure to individual odors may be largely without effect onthe ability to detect that odor, but they fail to confirm earlierfindings of dense degeneration in selected areas of the mitralcell layer after prolonged odor exposure.     

Microbial exposure during early human development primes fetal immune cells

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Single exposure to radiation produces early anti-angiogenic effects in mouse aorta

Radiation exposure can increase the risk for many non-malignant physiological complications, including cardiovascular disease. We have previously demonstrated that ionizing radiation can induce endothelial dysfunction, which contributes to increased vascular stiffness. In this study, we demonstrate that gamma radiation exposure reduced endothelial cell viability or proliferative capacity using an in vitro aortic angiogenesis assay. Segments of mouse aorta were embedded in a Matrigel-media matrix 1 day after mice received whole-body gamma irradiation between 0 and 20 Gy. Using three-dimensional phase contrast microscopy, we quantified cellular outgrowth from the aorta. Through fluorescent imaging of embedded aortas from Tie2GFP transgenic mice, we determined that the cellular outgrowth is primarily of endothelial cell origin. Significantly less endothelial cell outgrowth was observed in aortas of mice receiving radiation of 5, 10, and 20 Gy radiation, suggesting radiation-induced endothelial injury. Following 0.5 and 1 Gy doses of whole-body irradiation, reduced outgrowth was still detected. Furthermore, outgrowth was not affected by the location of the aortic segments excised along the descending aorta. In conclusion, a single exposure to gamma radiation significantly reduces endothelial cell outgrowth in a dose-dependent manner. Consequently, radiation exposure may inhibit re-endothelialization or angiogenesis after a vascular injury, which would impede vascular recovery.     

Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight

Dietary cadmium exposure was recently found to alter DNA methylation in adults, but data on effects early in life are lacking. Our objective was to evaluate associations between prenatal cadmium exposure, DNA methylation and birth weight. In total 127 mother-child pairs from rural Bangladesh were studied. For comparison, we included 56 children at 4.5 y. Cadmium concentrations in mothers’ blood (gestational week 14) and children’s urine were measured by ICPMS. Global DNA methylation was analyzed by Infinium HumanMethylation450K BeadChip in cord blood and children’s blood. Maternal cadmium exposure was associated with cord blood DNA methylation (p-value < 10^–16). The association was markedly sex-specific. In boys, 96% of the top 500 CpG sites showed positive correlations (r_S-values > 0.50), whereas most associations in girls were inverse; only 29% were positive (r_S > 0.45). In girls we found overrepresentation of methylation changes in genes associated with organ development, morphology and mineralization of bone, whereas changes in boys were found in cell death-related genes. Several individual CpG sites that were positively associated with cadmium were inversely correlated with birth weight, although none statistically significant after correction for multiple comparisons. The associations were, however, fairly robust in multivariable-adjusted linear regression models. We identified CpG sites that were significantly associated with cadmium exposure in both newborns and 4.5-y-old children. In conclusion, cadmium exposure in early life appears to alter DNA methylation differently in girls and boys. This is consistent with previous findings of sex-specific cadmium toxicity. Cadmium-related changes in methylation were also related to lower birth weight.     

Persistent aluminum accumulation after prolonged systemic aluminum exposure

To determine the distribution of aluminum (A1) following systemic exposure, female New Zealand white rabbits were given 20 subcutaneous injections, over 4 weeks, of 0, 25, 50, 100, 200, or 400 μmol A1/kg/injection, as the lactate salt. They were sacrificed 5 weeks after completion of injections and selected tissues removed for graphite furnace atomic absorption analysis of tissue A1 content. Rabbits not receiving A1 injections had mean tissue A1 concentrations ranging from 1.5-7.4 μg/g. Bone was higher, 18.7 μg/g. All tissues, except for muscle, demonstrated an increase in A1 concentration correlating with the A1 exposure. After 400 μmol A1/kg/injection for 20 injections, tissue A1 concentrations were: bone 90, heart 12, kidney-cortex 1290, kidney-medulla 245, liver 246, lung 19, and spleen 465 μg A1/g. The average of the 5 central nervous system regions sampled (frontal grey, white, hippocampus, cerebellum, and spinal cord) rose 53% over controls. Determination of A1 in kidney, liver, or bone may be useful in diagnosis of A1 overload conditions in humans (dialysis encepthalopathy, dialysis osteomalacia, and parenteral nutrition-associated osteomalacia). The rabbit appears to be a useful model to further study A1 intoxication syndromes.     

Temporal changes in mitral cell response patterns during repeated odor exposure

The olfactory system of 17 goldfish was stimulated by natural odors, and from 31 mitral cells activity was extracellularly recorded as a response to the stimuli. 40 experiments were available for evaluation because nine of the 31 cells were investigated with respect to two different odors. The aim of this study was to examine the changes of the activity patterns during repeated runs of an experiment. 120 runs were taken in 15 experiments, 40 runs in 25 experiments, and 37 runs in 2 experiments. Nineteen out of the forty recordings showed patterned activities. In ten cases the patterns remained constant in all runs, while pattern changes occurred in nine cases. These changes sometimes happened abruptly after the first run or developed gradually over up to forty runs in other cases. Possible causes of the pattern changes are discussed.     

Sex-specific effects of gonadal steroids on conspecific odor preference in the rat

Effects of gonadal steroids on conspecific odor preference for either (1) sexually active male or active female, (2) sexually active or gonadectomized (gdx) males, (3) sexually active or gdx females, and (4) gdx males or gdx females were determined in male and female rats in a three-chamber apparatus. For the first test, gdx females were made sexually active by treatments with estradiol benzoate (EB) and progesterone (P), and sexually active males were selected by prior screening. Sexually active males and females preferred opposite-sex odor over same-sex odor. Odor of sexually active opposite-sex conspecifics was preferred over that of inactive ones. Immediately after the completion of the first test, sexually active males were gdx and females were left without hormonal treatment. Second and third tests were carried out 2 and 5 weeks after the first test. In the second test, gdx males preferred odor of sexually active males rather than that of receptive females (male-directed preference); in the third test, both males and females showed no preference when tested with four stimulus pairs. The final tests were carried out in gdx males with EB and P, and gdx females with 2-week exposure to testosterone (T). Males with EB and P showed a male-directed preference again, whereas T-treated females kept their own female preference. Injection of EB alone to gdx males did not induce any preference. The present study clearly demonstrated sex difference in conspecific odor preference. Although both male and female preferences depend on their circulating sex steroids, the direction of male preference is more susceptible to their hormonal states, compared to that of females.     

Neural and behavioral changes in rats following continuous exposure to an odor

Summary Continuous exposure of young rats to the almond-like odor of acetophenone or cyclohexanone for up to 4 months, resulted in distinct but similar patterns of degenerating mitral cells in their olfactory bulbs. Rats favored their exposure odor in olfactory preference tests (Fig. 2) and their acuity for it was not altered (Fig. 3). However, they appeared to exhibit a deficit in detecting a similar but novel odor. The results suggest that the remaining normal mitral cells in the bulbs of these animals are those stimulated by the exposure odor. Cells which show signs of degeneration (Fig. 4) may receive little or no input from the periphery. Controls exposed to a similar but non-odorous environment showed evidence of non-selective mitral cell degeneration. In addition they had a lower acuity for acetophenone and cyclohexanone than animals reared in a normal rat colony (Fig. 3). Anatomical and behavioral data from odor exposed and control groups, suggest that partial regeneration of altered mitral cells may have occurred during a 5 month period following exposure. Overall the results provide further evidence for a topographical projection of the olfactory receptor epithelium onto the olfactory bulb and spatial coding of different odors in the bulb.     

Modality-specific neural effects of selective attention to taste and odor

The insular cortex is implicated in general attention and in taste perception. The effect of selective attention to taste on insular responses may therefore reflect a general effect of attention or it may be (taste) modality specific. To distinguish between these 2 possibilities, we used functional magnetic resonance imaging to evaluate brain response to tastes and odors while subjects passively sampled the stimuli or performed a detection task. We found that trying to detect a taste (attention to taste) resulted in activation of the primary taste cortex (anterior and mid-dorsal insula) but not in the primary olfactory cortex (piriform). In contrast, trying to detect an odor (attention to odor) increased activity in primary olfactory but not primary gustatory cortex. However, we did identify a region of far anterior insular cortex that responded to both taste and odor "searches." These results demonstrate modality-specific activation of primary taste cortex by attention to taste and primary olfactory cortex by attention to odor and rule out the possibility that either response reflects a general effect of attentional deployment. The findings also support the existence of a multimodal region in far anterior insular cortex that is sensitive to directed attention to taste and smell.     

Persistent biologic actions of insulin on cultured fetal human fibroblasts

Summary Monolayer cultures of fetal human fibroblasts, preincubated in serum-free culture medium overnight (about 18 hr), were incubated with insulin (0.1 to 100 mU per ml), then washed and incubated in an insulin-free medium. The effect of insulin on glucose utilization, uridine incorporation into RNA and leucine incorporation into protein was maintained after removal of insulin and washing. For both glucose utilization and uridine incorporation into RNA, this effect was demonstrated at physiologic levels of insulin (0.1 mU per ml). When anti-insulin serum was added to the cultures after the cell preincubated with insulin were washed, this effect was greatly attenuated. This lasting effect of insulin was probably not due to nonspecifically bound insulin becoming available to the cells. Binding of¹²⁵I-monoiodoinsulin was examined in monolayer cultures of fetal human fibroblasts. When unlabeled insulin was present at about 1 mU per ml concentration, 50% displacement of monoiodoinsulin occured. When fibroblasts were incubated with monoiodoinsulin and then removed from the radioactive medium, initial dissociation of the bound hormone occurred rapidly but then reached a plateau. This prolonged insulin effect appears to result from persistent binding of insulin to its receptor. Supported in part by PHS Grants AM-02456, AM-05020 and AM-15312, by the Kroc Foundation and by the Diabetes Center (AM-17047). Supported in part by Research Career Development Award AM-47142 from NIAMDD.     

Duration-dependent effects of nicotine exposure on growth and AKT activation in human kidney epithelial cells

Exposure to nicotine is known to cause adverse effects in many target organs including kidney. Epidemiological studies suggest that nicotine-induced kidney diseases are prevalent worldwide. However, the impact of duration of exposure on the nicotine-induced adverse effects in normal kidney cells and the underlying molecular mechanism is still unclear. Hence, the objective of this study was to evaluate both acute and long-term effects of nicotine in normal human kidney epithelial cells (HK-2). Cells were treated with 1 and 10 µM nicotine for acute and long-term duration. The result of cell viability showed that the acute exposure to 1 µM nicotine has no significant effect on growth. However, the 10 µM nicotine caused significant decrease in the growth of HK-2 cells. The long-term exposure resulted in significantly increased cell growth in both 1 and 10 µM nicotine-treated groups. Analysis of cell cycle and expression of marker genes related to proliferation and apoptosis further confirmed the effects of nicotine. Additionally, the analysis of growth signaling pathway revealed the decreased level of pAKT in cells with acute exposure whereas the increased level of pAKT in long-term nicotine-exposed cells. This suggests that nicotine, through modulating the AKT pathway, controls the duration-dependent effects on the growth of HK-2 cells. In summary, this is the first report showing long-duration exposure to nicotine causes increased proliferation of human kidney epithelial cells through activation of AKT pathway.     

Acute effects of 50 Hz magnetic field exposure on human visual task and cardiovascular performance

One hundred subjects, males and females with ages ranging between 18 and 48 years, were studied under both field-exposed and sham-exposed conditions. A 50 Hz, 100 μT magnetic field (MF) was used. To examine the effect of field exposure on performance, a two-alternative, forced-choice, duration-discrimination task with three levels of difficulty was used. The subject's task was to decide which of two sequentially presented light flashes had the longer duration. The standard duration was 50 ms, and the alternative durations were 65, 100, or 125 ms. Both reaction time and percentage of correct responses were recorded for each subject. MF and sham exposure were for 9 min each. Blood pressure and heart rate were also measured before and following MF exposure and sham-exposure trials. The study was performed double blind, with the exposure order counterbalanced. Compared to sham exposure, MF exposure significantly decreased reaction time on the hardest level of the performance task. MF exposure did not reliably affect percentage correct or cardiovascular performance. It was demonstrated that a relatively high level of statistical power was the basis for the observed MF effect, and the need to pay closer attention to power levels in future research is discussed. © 1996 Wiley-Liss, Inc.