Neuropsychological outcomes in children of mothers with epilepsy.

The study investigated the nature of the effects of maternal epilepsy on cognitive performance of the offspring. One hundred fifty-four children of mothers with epilepsy aged 5 to 11 years (study group), along with 130 control children, comparable with respect to IQ, socio-economic status, age, and gender underwent a neuropsychological assessment using subtests from the NEPSY: A Developmental Neuropsychological Assessment, tapping attentional, auditory-verbal, visuomotor, fine motor, and memory abilities. The study group scored significantly lower than the controls on measures of attention, memory, and fine-motor function. Deficits were more marked in but not limited to the subset of the study group exposed to maternal medication in utero. Group differences on auditory attention were found only in younger children. Valproate-exposed children obtained lower scores on sentence repetition, as well as on the more demanding part of a test of auditory attention, than other children in the study group, suggesting weaknesses in working memory in the former subgroup. Confounding by maternal epilepsy type and polytherapy complicate interpretation of this finding. Differences between subsets of children not exposed to anti-epileptic drugs in utero and controls suggest that both drug exposure and genetic factors may contribute to cognitive deficits associated with maternal epilepsy.     

Impact of dietary exposure to food contaminants on the risk of Parkinson's disease

This study aimed to investigate the association of Parkinson's disease (PD) with dietary exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg) in a community with increased exposure levels. A total of 79 clinically verified idiopathic PD cases and 154 controls matched by sex and age were examined in this case-control study in the Faroe Islands. Blood and hair samples were collected and a questionnaire recorded lifetime information on residence, dietary habits, smoking history, and occupational exposure to solvents, pesticides, and metals. Both unconditional and conditional logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI) in regard to relevant exposure variables. Increased ORs for dietary intakes of whale meat and blubber during adult life were statistically significant. The ORs for occupational exposure to solvents, pesticides and metals also suggested an increased risk for PD. Current serum concentrations of summation operator PCB and related contaminants suggested slightly increased ORs, although only beta-hexachlorocyclohexane (beta-HCH) was statistically significant. Increased intake of whale meat and blubber in adult life was significantly associated with PD, thus suggesting a positive association between previous exposure to marine food contaminants and development of PD.     

Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity

Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986-1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.     

Neurotoxicology of PCBs and related compounds.

Polychlorinated biphenyls (PCBs) are a family of 209 chemicals with two linked phenyl rings and variable chlorination. They are clear oils at room temperature. They were produced from the 1930s until banned in the 1970s because of toxicity and evidence of widespread environmental contamination. They were used mostly as insulators in electrical equipment; their widespread occurrence in the environment is more a consequence of uncontrolled disposal than of deliberate dissemination. In Asia, there have been two outbreaks of poisoning due to cooking oil contaminated by thermally degraded PCBs. Studies in workers exposed chronically to "clean" PCBs, workers exposed acutely to thermally degraded PCBs in clean-up of fires, and adult patients in Asia who ingested contaminated rice oil consistently show slowed nerve conduction and sometimes show headache, lassitude, and other CNS symptoms. In children exposed to background levels in the US, those with the highest transplacental exposure show hypotonia and hyporeflexia at birth and slowed motor development through age two, a defect in visual memory processing at 7 mon, and defects in short term memory at 4 years. Despite the presence of PCBs in breast milk, no association between breast milk exposure and any measured outcome has been seen other than lower activity levels at 4 years among long term breast fed children at the highest PCB levels. In Asia, children who were in utero at or after the 1968 exposure in Japan or the 1979 exposure in Taiwan showed clinically evident developmental delay. In Taiwan, the children were shown to have a variety of ectodermal defects, but the association between these defects and developmental delay was weak.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropsychological symptoms of juvenile-onset batten disease: experiences from 2 studies

Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a progressive and fatal autosomal-recessive inherited lysosomal storage disorder of childhood. Core symptoms include vision loss, seizures, and mental and motor decline. This article presents data from 2 studies of neuropsychological function in juvenile neuronal ceroid lipofuscinosis. In the first cross-sectional pilot study, 15 children with genetic or clinicopathologic confirmation of juvenile neuronal ceroid lipofuscinosis completed a brief test of attention (mean age = 14.3 +/- 2.9 years, range = 8.75-18.74 years; 7 males, 8 females). Average attention performances were significantly below age-expected normative data. A second longitudinal study was then initiated to study neuropsychological function in greater depth, including change in function over time. The authors have enrolled 18 children to date (mean age = 12.88 +/- 3.59 years, range = 6.26-18.65; 11 males, 7 females). Of these, 5 children have completed a second (annual) re-evaluation. Results thus far indicate significant impairment in domains of auditory attention, memory, estimated verbal intellectual function, and verbal fluency. Neuropsychological impairment was significantly correlated with disease duration and with motor function as assessed by a disease-specific clinical neurologic rating scale. There was no significant difference between males and females in neuropsychological test performance. Neuropsychological function was worse among children with a positive seizure history. Juvenile neuronal ceroid lipofuscinosis-affected children exhibited significant and pervasive impairments on tests of auditory attention, verbal memory and repetition, verbal fluency, and an estimate of verbal intellectual ability. Preliminary follow-up data from an annual reassessment showed progressive declines in cognitive function, in particular on a task of working memory. Neuropsychological deficits are pervasive and progressive. Future research will focus on clarifying the relationship among disease duration, motor function, and neuropsychological performances, including the relative sensitivity of neuropsychological testing at different stages of motor impairment or disease duration.     

Neuropsychological effects of occupational exposure to polychlorinated biphenyls

In the context of a health surveillance program for former PCB-exposed workers of a transformer and capacitor recycling company in Germany, their family members, employees of surrounding companies and area residents a broad range of cognitive functions covering attention, executive processing, reasoning, memory and motor performance was examined. The study aimed at identifying potential adverse effects of PCB load on cognitive functions. Detailed analysis of PCB burden of the participants revealed rather high correlations of lower and higher chlorinated as well as dioxin-like PCBs. Nearly one half of the participants exhibited increased burden in all three PCB classes whereas only 33 out of 237 participants did not show any increased PCB burden. Thus, data analysis followed a two-fold strategy: (1) Based on studies providing data on PCB exposure of the German general population the PCB burden of every participant was classified as normal (percentile rank PR <95) or increased (PR ≥95). Increased burden with respect to lower (LPCBs) and higher chlorinated (HPCBs) as well as dioxin-like (dlPCBs) PCBs was assumed if a participant showed at least one congener surpassing the PR95 criterion for the respective congener class and (2) Overall plasma PCB level per congener class was used as measure of PCB load. In a multivariate approach using structural equation modelling and multiple regression analysis we found a significant impact of PCBs on word fluency and sensorimotor processing irrespective of the measure of PCB burden (PR95 criterion or overall plasma level). However, no effect of PCB burden on memory, attention, and cognitive flexibility could be demonstrated. Particularly, an increase of LPCBs was associated with an overall reduction of verbal fluency of letter and semantic word generation as well as word production based on a single or two alternating criteria. In addition, participants with increased burden of LPCBs exhibited a time-on-task effect in terms of a stronger decline of performance with increasing duration of the verbal fluency task. Moreover, we found adverse effects of HPCBs on Aiming and of dlPCBs on Line Tracking. Results are discussed in terms of (1) a decrease of cerebral dopamine (DA) with non-coplanar PCBs resulting in an impact on fronto-striatal cerebral structures subserving verbal fluency and motor processing, (2) a PCB-induced reduction of norepinephrine leading to the time-on-task effect with verbal fluency, and (3) adverse effects of PCBs on dopaminergic receptors in the cerebellum resulting in impaired fine motor function.     

Increased prenatal exposure to methylmercury does not affect the risk of Parkinson's disease

This study aimed to determine whether prenatal methylmercury (MeHg) exposure is a risk factor for Parkinson's disease (PD). A total of 172 clinically confirmed PD cases and 1018 controls matched by vital status, sex and age were included. The cases were ascertained in 1995 or were diagnosed during 1995-2005 in the Faroe Islands where the prevalence of PD is twice as high as elsewhere in northern Europe. Because the main single source of increased MeHg exposure in the Faroes is whale meat, retrospective exposure assessment was possible using detailed whaling records, rules of whale meat distribution and census lists. The share for each resident was calculated from the total amount of whale meat landed divided by the number of residents in the district entitled to a share. Utilizing the calculated share per resident at the mother's residence prior to the date of parturition, maternal body burden profiles were calculated as the average hair Hg concentration during the whole pregnancy, during the third trimester, and at the beginning of the third trimester. The exposures were compared between cases and controls using Mantel-Haenszel odds ratios (ORs), chi2 and logistic regressions. All analytical methods gave ORs close to 1.0, none of them approaching statistical significance. The upper confidence limit was clearly below 2.0 in all analyses. No significant association between PD and prenatal MeHg exposure was found in this study, thus providing no support for prenatal MeHg exposure as an important risk factor that might explain the doubling of PD prevalence in this population.     

Polychlorinated Biphenyls PCB 153 and PCB 126 Impair the Glutamate–Nitric Oxide–cGMP Pathway in Cerebellar Neurons in Culture by Different Mechanisms

Polychlorinated biphenyls (PCBs) are persistent organic pollutants present in human blood and milk. Exposure to PCBs during pregnancy and lactation leads to cognitive impairment in children. Perinatal exposure to PCB 153 or PCB 126 impairs the glutamate–nitric oxide–cGMP pathway in cerebellum in vivo and learning ability in adult rats. The aims of this work were: (1) to assess whether long-term exposure of primary cultures of cerebellar neurons to PCB 153 or PCB 126 reproduces the impairment in the function of the glutamate–nitric oxide–cGMP pathway found in rat cerebellum in vivo; (2) to provide some insight on the steps of the pathway affected by these PCBs; (3) to assess whether the mechanisms of interference of the pathway are different for PCB 126 and PCB 153. Both PCB 153 and PCB 126 increase basal levels of cGMP by different mechanisms. PCB 126 increases the amount of soluble guanylate cyclase while PCB 153 does not. PCB 153 reduces the amount of calmodulin while PCB 126 does not. Also both PCBs impair the function of the glutamate–nitric oxide–cGMP pathway by different mechanisms, PCB 153 impairs nitric oxide-induced activation of soluble guanylate cyclase and increase in cGMP while PCB 126 does not. PCB 126 reduces NMDA-induced increase in calcium while PCB 153 does not. When PCB 153 and PCB 126 exhibit the same effect, PCB 126 was more potent than PCB 153, as occurs in vivo.     

Developmental exposure to polychlorinated biphenyls PCB153 or PCB126 impairs learning ability in young but not in adult rats

Polychlorinated biphenyls (PCBs) are persistent organic pollutants present in the food chain and in human blood and milk. Exposure to PCBs during pregnancy and lactation leads to cognitive impairment in children. The underlying mechanisms remain unclear. Some PCBs are endocrine disrupters. The aim of this work was to assess whether exposure of rats to PCB126 (dioxin-like) or PCB153 (non-dioxin-like) during pregnancy and lactation affects the ability of the pups to learn a Y maze conditional discrimination task and/or the function of the glutamate–nitric oxide (NO)–cGMP pathway in brain in vivo when the rats are young (3 months) or adult (7–8 months). After finishing the learning experiments, the function of the pathway was analysed in the same rats by in vivo brain microdialysis. The results obtained show that perinatal exposure to PCB153 or PCB126: (1) impairs learning ability in young but not in adult rats, (2) impairs the glutamate–NO–cGMP pathway function in cerebellum in vivo in young but not in adult rats and (3) affect these parameters in males and females similarly. PCB126 is around 10 000-fold more potent than PCB153. In control rats the function of the glutamate–NO–cGMP pathway and learning ability are lower in adult than in young rats. These age-related differences are not present in rats exposed to PCBs. The impairment of the glutamate–NO–cGMP pathway function induced at young age by developmental exposure to the PCBs could be one of the mechanisms contributing to the cognitive impairment found in children whose mothers ingested PCB-contaminated food during pregnancy and lactation.     

Rats exposed prenatally to alcohol exhibit impairment in spatial navigation test

Prenatal exposure to ethanol causes learning disabilities and low I.Q. scores. The objective of the present studies was to investigate whether exposure of rats to ethanol in utero, would induce a deficit in spatial memory in adult life. Pregnant rats were fed with an ethanol diet from day 1 of pregnancy till parturition. Control rats were either pair-fed with an isocaloric sucrose diet or were fed with lab-chow ad libitum. On the first day of birth, offspring exposed to ethanol in utero were placed with a control mother fed with lab-chow, while offspring of the lab-chow fed dams were placed with ethanol-treated dams. At 40, 60 and 90 days postnatally, behavioral testing was performed using the Morris swim maze, a test of spatial memory. Results indicated that the offspring exposed to ethanol in utero presented deficits in spatial memory processes. Ethanol did not completely block the learning of the swim maze task but the alcohol-exposed offspring exhibited longer latencies to perform the task, swam longer distances prior to locating and climbing onto the platform, and when the platform was removed, searched for it in all 4 quadrants of the pool. Restricted caloric intake during gestation and maternal behavior in early postnatal life also induced deficits in the performance on the swim maze task. However, these deficits were mild and short-lasting being absent at 60 and 90 days of age. In contrast, the deficits induced by ethanol were more severe and longer-lasting, being present in adult life.     

Association of maternal genital and reproductive infections with verbal memory and motor deficits in adult schizophrenia

Maternal exposure to genital and reproductive infections has been associated with schizophrenia in previous studies. Impairments in several neuropsychological functions, including verbal memory, working memory, executive function, and fine-motor coordination occur prominently in patients with schizophrenia. The etiologies of these deficits, however, remain largely unknown. We aimed to assess whether prospectively documented maternal exposure to genital/reproductive (G/R) infections was related to these neuropsychological deficits in offspring with schizophrenia and other schizophrenia spectrum disorders. The cases were derived from a population-based birth cohort; all cohort members belonged to a prepaid health plan. Cases were assessed for verbal memory, working memory, executive function, and fine-motor coordination. Compared to unexposed cases, patients exposed to maternal genital/reproductive infection performed more poorly on verbal memory, fine-motor coordination, and working memory. Stratification by race revealed associations between maternal G/R infection and verbal memory and fine-motor coordination for case offspring of African-American mothers, but not for case offspring of White mothers. Significant infection-by-race interactions were also observed. Although independent replications are warranted, maternal G/R infections were associated with verbal memory and motor function deficits in African-American patients with schizophrenia.     

The relation of environmental contaminants exposure to behavioral indicators in Inuit preschoolers in Arctic Quebec

Although lead (Pb) exposure has been identified as an important risk factor in child behavioral development, less is known regarding the relation between child behavior and exposure to polychlorinated biphenyls (PCBs) and mercury (Hg). Inuit children are particularly exposed to these chemicals and the aim of this study was to investigate the association between prenatal and postnatal exposure to Pb, PCBs, Hg and several aspects of behavioral function in Inuit preschoolers. The sample consisted of one hundred and ten 5-year-old Inuit children from Arctic Quebec. An umbilical cord blood sample was used to document prenatal exposure to Pb, PCBs and Hg. Child blood samples were collected at age 5 and the same contaminants were measured. A modified version of the Infant Behavior Rating Scale from the Bayley Scales of Infant Development-II was used to assess child behavior through examiners’ ratings. Furthermore, attention, activity and emotional outcomes were assessed through behavioral coding of video recordings taken during fine motor testing. Pb exposure during childhood was associated with examiners ratings of greater impulsivity, irritability and with coding of observed inattention. Prenatal exposure to PCB 153 correlated with the examiners ratings of increased state of unhappiness and anxiety during the testing session, which was corroborated from video coding since cord PCB 153 was related to fewer manifestations of positive affects. No association was found with Hg exposure. These data corroborated those from previous Pb cohort studies and revealed an association between prenatal PCBs exposure and emotional outcomes in preschoolers.     

Perinatal exposure to environmental polychlorinated biphenyls sensitizes hippocampus to excitotoxicity ex vivo

Ortho-substituted polychlorinated biphenyls (PCBs) are a concern to human developmental health. Rat dams were exposed to an environmentally relevant mixture of PCBs, Aroclor 1254, or pure congener PCB 95 (6 mg/kg/day) during the perinatal period (GD 5 through PD 21). Hippocampal slices prepared from offspring 1-3 weeks post-weaning were tested for persisting changes in sensitivity to the excitotoxicant picrotoxin. Hippocampal slices were placed on multielectrode arrays. Field excitatory postsynaptic potentials (fEPSPs) were recorded from Schaffer Collateral/Commissural fibers in striatum radiatum of the CA1 region in response to single pulse stimuli. After recording baseline excitability, GABA(A) receptors were blocked by inclusion of picrotoxin (100 μM) in the aCSF perfusate. Picrotoxin produced negligible changes in fEPSP slope in slices isolated from offspring exposed to vehicle, whereas slices from either PCB test group invariably showed >200% (p<0.01) synaptic facilitation. Picrotoxin produced prominent after-discharges (epileptic wave forms) in the evoked potentials measured from PCB exposed, but not control, hippocampal slices. These results show that developmental exposure to non-coplanar PCBs is sufficient to produce changes in synaptic plasticity that can be unmasked in the presence of GABA(A) receptor deficits that persist 1-3 weeks after exposure ceased. Developmental exposure to PCBs may sensitize seizure susceptibility postnatally, especially in susceptible populations with GABA(A) receptor signaling deficits.     

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and neuropsychological status among older adults in New York

Polybrominated diphenyl ethers (PBDEs) are emerging environmental contaminants, but little is known about their possible human health effects. The objective of this study is to evaluate the association between exposure to PBDEs and neuropsychological function among older adults and the possibility of effect modification with polychlorinated biphenyls (PCBs). Serum samples were analyzed for concentrations of 9 PBDE and 30 PCB congeners and 34 tests of cognitive and motor function, affective state, and olfactory function were assessed among 144 men and women of 55-74 years of age. After adjustment for relevant confounders, no overall associations were observed between the sum of the PBDE congener concentrations in serum (∑ PBDE) and scores on the neuropsychological tests. However, statistically significant interactions were found between PBDEs and PCBs for some measures of verbal learning and memory. Among persons with ∑ PCB concentrations at or above the median of 467 ppb (lipid basis), an increase in ∑ PBDE concentrations from the 25th to 75th percentile was associated with decreases between 7% and 12% on scores for certain subscales of the California Verbal Learning Test. In contrast, no statistically significant associations were observed for PBDEs among persons with ∑ PCB levels below the median. The results suggest that PBDEs and PCBs may interact to affect verbal memory and learning among persons 55-74 years old. This is the first study to evaluate the neuropsychological effects of PBDEs in adults and the possibility of synergy with PCBs in humans.     

Lactational and postnatal exposure to polychlorinated biphenyls induces sex-specific anxiolytic behavior and cognitive deficit in mice offspring

The central nervous system is affected by polychlorinated biphenyls (PCBs). Previous studies have indicated that developmental exposure to PCBs impairs behavioral performance and alters cognitive abilities. This study assessed the effects of lactational and postnatal exposure to a commercial PCBs mixture, Aroclor 1254 (A1254), on mice performing several neurobehavioral tasks including the open field test, novel object test, elevated plus maze test, Y‐maze test, and tail suspension test. In the open field test, PCBs treatment (6 and 18 mg/kg/day) was associated with increased movement, time duration, and frequency in the central zone in female but not male mice. PCBs‐treated female mice (6 and 18 mg/kg/day) also showed decreased novel object recognition, indicating impairment in recognition memory. Finally, we performed autoradiographic receptor binding assays for dopamine (DA) D₁ and D₂ receptors, dopamine transporter (DAT), and the N‐methyl‐D ‐aspartic acid (NMDA) receptor after behavioral tests to examine whether alterations occurred in the dopaminergic and NMDAergic systems of the brain. Our results showed that PCBs treatment did not change D₁ and D₂ receptors or DAT binding in the dorsal striatum of female mice. However, PCBs treatment significantly decreased NMDA receptor binding in the dorsal striatum, frontal cortex, cingulate cortex, and motor cortex, and CA3 and dentate gyrus (DG) of the hippocampus in female mice. Collectively, our results suggest that long‐term PCBs exposure can induce anxiolytic behavior, cognitive deficits, and changes of NMDA receptors. Synapse, 2011. © 2011 Wiley©Liss, Inc.     

Developmental exposure to a commercial PCB mixture (Aroclor 1254) produces a persistent impairment in long-term potentiation in the rat dentate gyrus in vivo

Developmental exposure to polycholorinated biphenyls (PCBs) has been associated with cognitive deficits in humans and laboratory animals. The present study sought to examine synaptic plasticity in the hippocampus, a brain region critical for some types of memory function, in animals exposed to PCBs early in development. Pregnant Long–Evans rats were administered either corn oil (control) or 6 mg/kg/day of a commercial PCB mixture, Aroclor 1254 (A1254) by gavage from gestational day (GD) 6 until pups were weaned on postnatal day (PND) 21. In adult male offspring (3–6 months of age), field potentials evoked by perforant path stimulation were recorded in the dentate gyrus under urethane anesthesia. Input/output (I/O) functions were assessed by averaging the response evoked in the dentate gyrus to stimulus pulses delivered to the perforant path in an ascending intensity series. Long-term potentiation (LTP) was induced by delivering a series of brief high frequency (400 Hz) train bursts to the perforant path at a moderate stimulus intensity and I/O functions were reassessed 1 h later. No differences in baseline synaptic population spike (PS) and minor effects on excitatory postsynaptic potential (EPSP) slope amplitudes were discerned between the groups prior to train delivery. Post-train I/O functions, however, revealed a 50% decrement in the magnitude of LTP in PCB-exposed animals. These data are the first to demonstrate persistent decrements in hippocampal synaptic plasticity in the intact animal following developmental exposure to PCBs. Disruption of early brain ontogeny due to developmental PCB exposure may underlie perturbations in the neurological substrates that support synaptic plasticity and contribute to deficits in LTP and learning that persist into adulthood.     

Developmental disruptions and behavioral impairments in rats following in utero RNAi of Dyx1c1

Developmental malformations of cortex have been shown to co-occur with language, learning, and other cognitive deficits in humans. Rodent models have repeatedly shown that animals with such developmental malformations have deficits related to auditory processing and learning. More specifically, freeze-lesion induced microgyria as well as molecular layer ectopias have been found to impair rapid auditory processing ability in rats and mice. In humans, deficits in rapid auditory processing appear to relate to later impairments of language. Recently, genetic variants of four different genes involved in early brain development have been proposed to associate with an elevated incidence of developmental dyslexia in humans. Three of these, DYX1C1, DCDC2, and KIAA0319, have been shown by in utero RNAi to play a role in neuronal migration in developing neocortex. The present study assessed the effects of in utero RNAi of Dyx1c1 on auditory processing and spatial learning in rats. Results indicate that RNAi of Dyx1c1 is associated with cortical heterotopia and is suggestive of an overall processing deficit of complex auditory stimuli in both juvenile and adult periods (p=.051, one-tail). In contrast, adult data alone reveal a significant processing impairment among RNAi treated subjects compared to shams, indicating an inability for RNAi treated subjects to improve detection of complex auditory stimuli over time (p=.022, one-tail). Further, a subset of RNAi treated rats exhibited hippocampal heterotopia centered in CA1 (in addition to cortical malformations). Malformations of hippocampus were associated with robust spatial learning impairment in this sub-group (p<.01, two-tail). In conclusion, in utero RNAi of Dyx1c1 results in heterogeneous malformations that correspond to distinct behavioral impairments in auditory processing, and spatial learning.     

Adverse health effects of PCBs on fine motor performance – Analysis of a neurophysiological pathway in the HELPcB surveillance program

Since research literature indicates neurotoxic health effects of polychlorinated biphenyls (PCBs), it is necessary to identify by which mechanism PCBs might affect the human central nervous system and human behavior. In the present study, a neurophysiological pathway is assumed to explain the negative association of PCB exposure and performance in fine motor tasks mediated by the level of the dopamine (DA) metabolite homovanillic acid (HVA). A total of 113 occupationally PCB exposed workers and their relatives from an occupational health monitoring program were examined (89.4 % men). PCBs were analyzed in plasma via human biomonitoring and HVA was assessed in urine. The motor performance series was used to measure two dimensions of fine motor skills with 5 subgroups (accuracy: steadiness, line tracking accuracy; speed: line tracking speed, aiming, tapping). The direct effects of PCBs on fine motor performance and the indirect effects of PCBs on fine motor performance via DA metabolite HVA were tested with multiple regressions. We found significant effects for the accuracy dimension, namely a negative direct effect of PCBs on line tracking accuracy mediated by HVA. Further, an indirect effect could be found for PCBs with steadiness accuracy through HVA. There were no significant effects related to fine motor performances in the speed dimension. These results provide first indications for an underlying neurochemical pathomechanism involving the dopamine system of PCB-related deterioration of fine motor performance regarding accuracy.     

Association between prenatal exposure to methylmercury and visuospatial ability at 10.7 years in the seychelles child development study

The Seychelles Child Development Study was designed to test the hypothesis that prenatal exposure to MeHg from maternal consumption of a diet high in fish is detrimental to child neurodevelopment. To date, no consistent pattern of adverse associations between prenatal exposure and children's development has appeared. In a comprehensive review of developmental studies involving MeHg, a panel of experts recommended a more consistent use of the same endpoints across studies to facilitate comparisons. Both the SCDS and the Faeroe Islands studies administered the Bender Visual Motor Gestalt Test. However, the method of test administration and scoring used was different. We repeated the test on the SCDS Main Study children (mean age 10.7 years) using the same testing and scoring procedure reported by the Faeroe studies to obtain Copying Task and Reproduction Task scores. We found no association between prenatal MeHg exposure and Copying Task scores which was reported from the Faeroese study. However, our analysis did show a significant adverse association between MeHg and Reproduction Task scores with all the data (p=0.04), but not when the single outlier was removed (p=0.07). In a population whose exposure to MeHg is from fish consumption, we continue to find no consistent adverse association between MeHg and visual motor coordination.     

Repeated exposure of adult rats to Aroclor 1254 induces neuronal injury and impairs the neurochemical manifestations of the NMDA receptor-mediated intracellular signaling in the hippocampus

Aroclor 1254 is a mixture of polychlorinated biphenyls (PCBs), a class of environmental toxins which cause a wide spectrum of neurotoxic effects. Learning and memory deficits are the profound effects of PCBs which may be related to hippocampal dysfunction. To get insight into the underlying neurochemical mechanisms, we employed the microdialysis technique to investigate the effect of repeated exposure of adult male Wistar rats to Aroclor 1254 (10 mg/kg b.w., daily, ig., for 14 days), on the neurochemical parameters of NMDA receptor-mediated glutamatergic signaling in the hippocampus in vivo assessed using the microdialysis technique. The results demonstrated that exposure to Aroclor 1254, which was associated with substantial neuronal damage and loss in the hippocampus, markedly decreased the NMDA-induced extracellular accumulation of newly loaded ⁴⁵CaCl₂, cGMP and glutamate, and reduced the basal content of the NO precursor, arginine, indicating inhibition of the NMDA/NO/cGMP pathway. Aroclor 1254 exposure also decreased the basal microdialysate content of glutamate and glutamine, which may cause inadequate supply of the neurotransmitter glutamate, while the level of two other neuroactive amino acids, aspartate or taurine was not affected by the exposure. The results underscore neuronal lesion and inhibition of NMDA receptor-mediated glutamatergic signaling in hippocampus as a potential major contributor to the cognitive deficits associated with exposure to PCB.