Biomedical subjects

Susan L Schantz

Publications and source records attributed to Susan L Schantz.

14 recordsLinked to original sources

PubMed2006

Alterations in DRH and DRL performance in rats developmentally exposed to an environmental PCB mixture.

Schedule-controlled responding was examined in offspring of rats exposed to a PCB mixture formulated to mimic the PCB congener profile in fish from the Fox River in Green Bay, WI. Female rats were administered 0, 1, 3, or 6 mg/kg/day of the PCB mixture beginning four weeks prior to breeding until weaning on postnatal day 21. When offspring were approximately 235 days old, they were tested on three different schedules of a differential reinforcement of high rate (DRH) operant task (DRH 2:1, DRH 4:2, and DRH 8:4). DRH testing was followed by testing on the differential reinforcement of low rate (DRL) operant task in which rats had to inhibit responding until 15 s had elapsed (DRL 15) from the previous response in order to obtain a food reinforcer. After completion of DRL 15 testing, 3 days of extinction testing were conducted (DRL EXT) during which no reinforcers were delivered. Developmental exposure to the higher PCB doses resulted in shorter inter-response times (IRTs) and shorter response durations during DRH 8:4, which translated into a greater percentage of reinforced trials. For DRL 15, no significant exposure-related effects were observed on the number of responses or reinforcers earned, or the number or proportion of responses with long or short inter-response times during acquisition or steady state performance. However, during DRL EXT, rats developmentally exposed to the highest PCB dose responded more than controls, produced significantly more short IRT responses, and had a significantly lower proportion of long IRT responses. Overall, exposure to this PCB mixture resulted in increased responding which was suggestive of a deficit in inhibitory control.

Analysis of Variance↗

PubMed2006

Motor function following developmental exposure to PCBS and/or MEHG.

Recent studies raise concern for combined exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg), two environmental contaminants that are found in fish and seafood. Past accidental poisonings in humans show that exposure to high levels of either contaminant is associated with motor impairments, including alterations in cerebellar functions such as balance and coordination. Epidemiological studies of lower level exposures suggest some neuromotor impairment in exposed children, but the majority of these studies have focused on cognitive endpoints rather than examining a full-range of motor function. In particular, the cerebellum could be a sensitive target for combined PCB and MeHg toxicity. MeHg exposure during development damages the cerebellum along with cortical areas, and PCBs may also cause cerebellar damage via thyroid hormone disruption during development. In addition, in vitro studies report interactive effects of PCBs and MeHg on ryanodine-sensitive calcium signaling. Ryanodine receptors are found especially within the cerebellum, and alterations in calcium signaling within the cerebellum could impair long-term depression and subsequent motor learning. This article reviews the motor impairments reported in humans and laboratory animals following exposure to PCBs and/or MeHg during development. There is need for a better understanding of the interactive effects of PCBs and MeHg, especially in regard to motor function.

Animals↗

PubMed2005

Auditory deficits in rats exposed to an environmental PCB mixture during development.

Previous studies have indicated that developmental exposure to polychlorinated biphenyls (PCBs) may result in hearing impairment in rats. The cochlea is the suggested site of action, based upon one study demonstrating a loss of outer hair cells on the basilar membrane, and another demonstrating deficits in distortion product otoacoustic emissions (DPOAEs). The current study was conducted to assess the possible ototoxic effects of a unique PCB mixture formulated to model the congener profile of PCBs found in fish consumed by a human population in northeastern Wisconsin. Female Long-Evans rats were dosed orally with the PCB mixture beginning 28 days prior to breeding and continuing until the pups were weaned. Dams were fed one-half of a cookie onto which was pipetted 0, 1, 3, or 6 mg/kg of the PCB mixture dissolved in a corn oil vehicle. On postnatal day (PND) 21, pups were weaned, and one male and one female from each litter were randomly selected for auditory assessment. DPOAEs were measured to assess cochlear function, and auditory brainstem responses (ABRs) were measured to determine effects on central nervous system auditory pathways. DPOAE amplitudes were decreased, and DPOAE and ABR thresholds were elevated across a range of frequencies in PCB-exposed rats. These results support and extend previous reports of auditory impairment in PCB-exposed rats. Developmental exposure to PCBs may also result in subtle auditory impairments in humans, and if so, this may contribute to some of the cognitive deficits that have been observed in epidemiological studies.

Administration, Oral↗

PubMed2005

Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg.

We recently reported that rats exposed to PCBs and MeHg during development were impaired on the rotating rod, a test of balance and coordination that is often indicative of cerebellar damage. In addition, developmental PCB exposure is known to dramatically reduce circulating thyroid hormone concentrations, which may have a negative impact on cerebellar development. Therefore, we investigated the effects of combined PCB and MeHg exposure on Purkinje cells and the cerebellum. The serum and brains from littermates of the animals tested on the rotating rod were collected at weaning, and we also collected brains from the adult animals at the end of motor testing. Four groups were studied: 1) vehicle controls, 2) PCBs only (Aroclor 1254, 6 mg/kg/d, oral), 3) MeHg only (0.5 ppm, in dams' drinking water), and 4) PCB+MeHg (at the same doses as in individual toxicant exposures). Female Long-Evans rats were exposed beginning 4 weeks prior to breeding with an unexposed male and continuing until postnatal day (PND) 16. There was a significant reduction in serum T4 and T3 concentrations in the PCB and PCB+MeHg pups on PND21. Golgi-impregnated Purkinje cells were examined in PND21 brains, but there were no significant exposure-related effects on primary dendrite length, branching area, or structural abnormalities. However, all three male exposure groups had a marginally significant increase in Purkinje cell height, which may suggest a subtle thyromimetic effect in the cerebellum. Cresyl-violet stained sections from the adult brains showed no exposure-related effects within paramedian lobule in Purkinje cell number, total lobule volume or layer volumes (molecular, granule cell and white matter layers). Evidence is provided for the dysregulation of expression of cerebellar ryanodine receptor (RyR) isoforms in PCB-exposed brains, and this could contribute to the rotating rod deficit by changing critical aspects of intracellular calcium signaling within the cerebellum.

Administration, Oral↗

PubMed2005

Formulation and characterization of an experimental PCB mixture designed to mimic human exposure from contaminated fish.

Each environmental exposure matrix contains a unique mixture of PCB congeners. Since several congener types have multiple and distinct biological actions, it is important to characterize congener profiles in exposure sources. The Fox River Environment and Diet Study (FRIENDS) is assessing the human health effects of consumption of PCB-contaminated fish from the Fox River in northeastern Wisconsin. Concurrent laboratory studies required the formulation of a dosing solution which closely mimicked the human PCB exposure from fish. PCB congener profiles from Fox River walleye were compared to profiles for various theoretical mixtures having different relative percentages of Aroclors by weight. The theoretical mixture which provided the best approximation of the Fox River fish PCB profile contained 35% 1242, 35% 1248, 15% 1254, and 15% 1260. A PCB mixture was formulated to match this theoretical construct, and the congener profile for the mixture of Aroclors was determined by capillary column gas chromatography with electron capture detection (GC/ECD). The relative percent of each congener was compared to the PCB congener profile of the theoretical Aroclor mixture and that for Fox River walleye. The specific congeners differed on average by 17% from the theoretical Aroclor mixture predicted values, and the specific congeners measured in the mixture were on average within 71% of those reported for Fox River fish. The mixture was found to have relatively low AhR activity but high RyR activity. Indirect comparisons suggest that in vivo toxicity was slightly greater than that for Aroclor 1254. This illustrates that Aroclor mixtures are useful for formulating dosing solutions which closely approximate actual environmental exposures.

Animals↗

PubMed2005

Delayed spatial alternation impairments in adult rats following dietary n-6 deficiency during development.

Dietary n-3 fatty acid (FA) deficiencies during development can cause learning and memory impairments, but the functional effects of dietary n-6 FA deficiencies, reflected in a lowered n-6/n-3 ratio, are less clear. We investigated the effects of maternal diets containing fish oils, resulting in lowered n-6/n-3 ratios, on a spatial working memory task in their offspring. Starting on gestational day 6, Sprague-Dawley timed-pregnant rats were placed on one of three experimental diets: control (unadulterated powdered rat chow), Pacific Ocean (PO) fish (powdered rat chow containing 20% (w/w) lyophilized PO salmon), or PO oil (powdered rat chow containing 6% (w/w) oil extracted from PO salmon). The 6% oil dose was selected because it is equivalent to the amount of oil in the 20% lyophilized fish diet. The experimental diets were fed until weaning on postnatal day (PND) 21, at which time all pups were placed on the rat chow diet. Starting on approximately PND77, one male and one female from each litter began a cognitive test battery using 2-lever operant chambers. PO groups failed to reach the same level of performance as the controls on the delayed spatial alternation (DSA) task and also showed decreased performance on delay trials. FA analyses of the diets found that the n-6/n-3 ratios for the PO fish and oil groups were reduced to 2.5 and 3.2, respectively, vs. 6.9 for controls. Analysis of brain tissue taken from pups on PND21 confirmed that the n-6/n-3 ratios within the brain were significantly reduced from 1.18 for controls to 0.87 and 0.90 for PO fish and oil groups, respectively. Specifically, the PO diets significantly increased long-chain n-3 FAs (20:5 n-3 and 22:6 n-3) and decreased long-chain n-6 FAs (20:4 n-6 and 22:4 n-6) in the brain. Thus, the observed delayed spatial alternation impairments in rats fed PO fish and fish oil are hypothesized to have resulted from the altered n-6/n-3 FA ratios.

Animals↗

PubMed2005

Lakes in crisis.

Explore the source record for details and available documents.

Animals↗

PubMed2004

Spatial alternation deficits following developmental exposure to Aroclor 1254 and/or methylmercury in rats.

Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are ubiquitous environmental contaminants that alter cognitive function in both humans and animals. Because PCBs and MeHg often occur together in the environment, it is important to understand whether these two contaminants have the potential to interact, causing additive or greater than additive effects. The current study examined the combined effects of gestational and lactational exposure to Aroclor 1254 (A1254), a commercial PCB mixture, and MeHg on a series of spatial alternation tasks including cued spatial alternation (CA), non-cued spatial alternation (NCA), and delayed spatial alternation (DSA) in rats using standard two-lever operant testing chambers. Pregnant Long-Evans rats received either 6 mg/kg A1254 pipetted onto a Keebler Vanilla Wafer cookie (PCB-only group), 0.5 ppm. MeHg dissolved in the drinking water (MeHg-only group), 6 mg/kg A1254 + 0.5 ppm. MeHg (PCB + MeHg group), or corn oil vehicle and normal tap water (control group) beginning 28 days prior to mating and continuing through postnatal day 16. One male and one female from each litter began testing on spatial alternation at approximately 110 days of age. Animals were reinforced for pressing the lever opposite that pressed on the previous trial. In general, animals exposed to A1254 and/or MeHg were impaired relative to control rats on the NCA and DSA tasks. Significant reductions in NCA performance were observed in the MeHg-only and PCB + MeHg groups, while significant reductions in DSA performance were observed in the PCB-only and MeHg-only groups. The PCB + MeHg group showed a similar magnitude reduction in performance on DSA, but this difference was not statistically significant due to increased variability in that group. The reductions in DSA performance were observed across most of the delays, indicating that memory impairments were not likely the cause of the deficit. Instead, the DSA deficits following exposure to A1254 and/or MeHg are indicative of either an associative or attentional impairment. The results from the current study indicate that combined exposure to PCBs and MeHg does not exacerbate the PCB- or MeHg-induced impairments on spatial alternation tasks.

Animals↗

PubMed2003

Motor impairment in rats exposed to PCBs and methylmercury during early development.

Epidemiological and laboratory studies indicate that polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) may have additive or interactive adverse effects on nervous system function. Prior studies have shown that high doses of MeHg target the cerebellum and impair balance and coordination, but the effects of PCBs on cerebellar function were unknown. In addition, the combined effects of PCBs and MeHg on cerebellar function have not been studied previously. Therefore, we investigated the effects of developmental exposure to PCBs, MeHg, or PCBs + MeHg on three motor tasks that involve cerebellar functions. Female Long-Evans rats were exposed to MeHg (0.5 ppm in drinking water), PCBs (6-mg/kg/d Aroclor 1254), PCBs + MeHg, or vehicle only beginning 4 weeks prior to breeding, through pregnancy, and continuing through postnatal day (PND) 16. Starting at approximately PND 60, one male and one female from each litter were tested on three motor tasks that involve cerebellar function. PCB + MeHg-exposed rats were impaired relative to the controls on a task requiring them to traverse a rotating rod. Rats exposed to PCBs alone were also somewhat impaired relative to the controls, whereas MeHg-exposed rats were not significantly different from the controls. There were no statistically significant deficits related to PCB or MeHg exposure on a vertical rope-climbing test or a parallel bar test. Our results demonstrate that the possibility of additive neurotoxic effects of PCBs and MeHg needs to be seriously considered.

Animals↗

PubMed2003

Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats.

Due to the estrogenic properties of soy-derived isoflavones, many postmenopausal women are using these compounds as a natural alternative to hormone replacement therapy (HRT). How isoflavones impact breast cancer in postmenopausal women is important, because a majority of breast cancer cases occur in this age group. Chemical induction of mammary tumors in female rats has been used to determine that exposure of the mammary gland to soy isoflavones prior to tumor induction is protective against tumor formation. Here we investigate the effect of dietary genistein on mammary tumors that have already formed. The study was designed to determine the action of dietary genistein in a low endogenous estrogen environment as is observed in postmenopausal women. Animals were ovariectomized (OVX) after mammary tumor development and were then placed into one of three treatment groups: positive-control (OVX+ estradiol implant), genistein (OVX+ 750 p.p.m. genistein) and negative-control (OVX alone). Tumors were distinguished as malignant or benign by histopathological examination and were further characterized as either estrogen-dependent or estrogen-independent using immunohistochemistry to identify the presence of both estrogen receptor (ER) alpha and the progesterone receptor (PR). Genistein at 750 p.p.m. increased the weight of estrogen-dependent adenocarcinomas in ovariectomized rats compared with the negative-control animals. Genistein treatment also resulted in a higher percentage of proliferative cells in tumors and increased uterine weights when compared with negative-control animals. Collectively, these effects are probably due to the estrogenic activity of genistein. Plasma genistein concentrations in animals fed the isoflavone-containing diet were at physiological levels relevant to human exposure. Estradiol concentrations in ovariectomized animals not receiving an estradiol supplement were similar to those observed in postmenopausal women. The data suggest that in an endogenous estrogen environment similar to that of a postmenopausal woman, dietary genistein can stimulate the growth of a mammary carcinogen MNU-induced estrogen-dependent mammary tumors.

Adenocarcinoma↗

PubMed2003

Effects of PCB exposure on neuropsychological function in children.

In the last decade advances in the analytic methods for quantification of polychlorinated biphenyls (PCBs) have resulted in widespread availability of congener-specific analysis procedures, and large amounts of data on PCB congener profiles in soil, air, water, sediments, foodstuffs, and human tissues have become available. These data have revealed that the PCB residues in environmental media and human tissues may not closely resemble any of the commercial PCB mixtures, depending on source of exposure, bioaccumulation through the food chain, and weathering of PCBs in the environment. At the same time, toxicological research has led to a growing awareness that different classes of PCB congeners have different profiles of toxicity. These advances in analytic techniques and toxicological knowledge are beginning to influence the risk assessment process. As the data from ongoing PCB studies assessing the mediators of neurobehavioral outcomes in children are published, the weight of evidence for PCB effects on neurodevelopment is growing. Studies in Taiwan, Michigan (USA), New York (USA), Holland, Germany, and the Faroe Islands have all reported negative associations between prenatal PCB exposure and measures of cognitive functioning in infancy or childhood. The German study also reported a negative association between postnatal PCB exposure and cognitive function in early childhood--a result that had not been found in previous studies. Only one published study in North Carolina (USA) has failed to find an association between PCB exposure and cognitive outcomes. Despite the fact that several more recent studies have used congener-specific analytic techniques, there have been only limited attempts to assess the role of specific PCB congeners or classes of congeners in mediating neurodevelopmental outcomes. From a statistical standpoint, attempts to determine the role of individual congeners in mediating outcomes are hampered by the fact that concentrations of most individual congeners are highly correlated with each other and with total PCBs. From a toxicological standpoint, these efforts are hampered by the fact that many of the PCB congeners present in human tissues have never been studied in the laboratory, and their relative potency to produce nervous system effects is unknown. More complete information on the health effects of various congeners or congener classes would allow more informed scientific and risk assessment decisions.

Child↗

PubMed2003

A longitudinal examination of factors related to changes in serum polychlorinated biphenyl levels.

Consumption of sport-caught fish from the Great Lakes is a recognized source of human exposure to polychlorinated biphenyls (PCBs). Understanding temporal changes in PCB body burden is crucial for evaluating exposure levels and augmenting validity of studies investigating their relationship to adverse health effects. Using data collected from 1980 to 1995, we evaluated longitudinal changes in serum PCB levels among 179 fisheaters and non-fisheaters of the Michigan Fisheater Cohort. Participants identified as fisheaters in 1980 ate 26 lb or more of sport-caught fish per year, whereas non-fisheaters ate less than 6 lb per year. We found a monotonic decline in serum PCB levels among all participants from a mean value of 24 ppb in 1980 to 12 ppb in 1994. This was paralleled by an 83% decrease in mean fish consumption among all participants over the same period. We combined demographic, lifestyle, and fish consumption information with PCB data and evaluated the data using regression models to identify predictors of PCB body burden over a 16-year period. Results of the mixed-effects linear regression model suggest that consumption of Lake Michigan fish before 1980, amount of sport-caught fish eaten in the past year, age, and year of data collection were significant determinants of current PCB body burden over the 16-year study period. PCB levels were particularly elevated for males who were classified as fisheaters in 1980, which may reflect higher levels of sport-caught fish consumption compared with female fisheaters.

Adult↗

PubMed2002

Perinatal exposure to Aroclor 1254 impairs distortion product otoacoustic emissions (DPOAEs) in rats.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that are a potential health hazard to human and wildlife populations. Low-frequency auditory impairments have previously been documented in Aroclor 1254 (A 1254)-exposed rats, including elevated behavioral auditory thresholds and decreased amplitude and prolonged latency auditory evoked brain stem responses (ABRs). Furthermore, outer hair-cell loss on the basilar membrane of the cochlea has been documented, demonstrating that the cochlea is a target organ for PCB ototoxicity. The current experiment assessed the effects of A1254 on cochlear function by measuring distortion product otoacoustic emissions (DPOAEs). ABRs were measured to determine the effects of A1254 on the central nervous system auditory pathways. Pregnant Long-Evans rats received either 0 or 6 mg/kg A1254 (po) in corn oil from gestation day 6 to lactational day 21. The auditory function of male and female offspring was assessed at approximately 18 months of age. The rats were anesthetized and a probe-unit, consisting of 2 insert earphones and a microphone, was positioned in the ear canal. DPOAE amplitudes were reduced and thresholds increased in the A1254-exposed rats. The deficits were most pronounced at the lowest frequencies tested (2.1-3.2 kHz), but deficits were also observed at higher frequencies (3.7-8.6 kHz). Males and females were equally affected at the lower frequencies, but females were more impaired at the higher frequencies. In contrast, ABR latencies and amplitudes were not altered by A1254 exposure. These findings provide the first functional evidence supporting a cochlear site of damage in PCB-induced hearing loss.

Animals↗

PubMedDate not supplied

Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial and visual reversal learning in rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that has been shown to alter spatial and visual learning following developmental exposure. The current study examined the effects of gestational and lactational exposure to TCDD on spatial and visual discrimination/reversal learning (spatial and visual RL) in rats using two-lever operant testing chambers. Pregnant Sprague-Dawley rats (10 per dose) received either 0 or 0.1 microg/kg TCDD per orem in corn oil from gestational day (GD) 10 to GD 16. One male and one female from each litter were tested beginning at 100 days of age. For spatial RL, animals were reinforced for pressing the lever associated with the correct spatial location (either left or right). For visual RL, the animals were reinforced for pressing the lever associated with the correct visual stimulus (either the illuminated or nonilluminated cuelight). After reaching 85% correct for two consecutive days, the opposite spatial location or visual cue was reinforced. Five reversals were conducted for spatial RL, and two reversals for visual RL. For spatial RL, there were no differences between the TCDD-exposed and control rats in total number of errors committed. However, an in-depth analysis of errors in four different phases of the learning process revealed that TCDD-exposed rats made more errors early in learning when they were just beginning to learn the new reinforcement contingencies. The importance of this increase in errors during the initial stage of learning is unclear, given that there was no increase in overall errors to criterion. For visual RL, there was a reduction in errors on original learning (OL) for TCDD-exposed males, while TCDD-exposed females exhibited a reduction in errors on the second reversal. Subsequent response pattern analyses revealed that the facilitation in performance was due to a more rapid transition through the early phase of learning. Why males were improved on OL and females were not until the second reversal is unknown, but the different patterns could reflect differences in learning style in male and female rats. In keeping with previous research, the results of the current study underscore the fact that (1) alterations in cognitive function observed following early TCDD exposure are very subtle and (2) under some conditions, learning is actually facilitated, rather than impaired, in TCDD-exposed animals.

Analysis of Variance↗