PCBS and Newborn Rat Pups
Due to the attention being paid to the environment and autism, it is not surprising to read about a study linking PCBs, polychlorinated biphenyls, to autism. The study is to be published this week in his week’s online Proceedings of the National Academy of Sciences; its senior author is neuroscientist Michael M. Merzenich of UCSF’s W.M. Keck Foundation Center for Integrative Neuroscience. Under study were not humans but newborn rats. It is abnormalities in the brain’s response to sounds in particular that connects this study to autism (that is to say, the rats in the study are said to have an “autism-like condition”—they are not autistic rat pups):
The scientists compared the auditory cortex and nerve signals of unexposed rat pups to pups exposed to one type of PCB during gestation and nursing. One of the most profound disruptions from the PCBs involved abnormalities in signals sent by the brain to inhibit or trigger reactions to sounds. The brain also had diminished capacity to learn and change how it responds to sounds.
Scientists believe that autistic children have such signaling imbalances.
They respond differently to sound and other sensations, and their communication and language skills are impaired.
“The animals could hear, but their brain’s representations of what they heard was grossly disturbed,” Merzenich said.
I find Professor Merzenich’s noting that the PCB-exposed rat pups had different responses to sound and sensations of interest. It is often apparent that my son hears—human speech, noise in the street—and does not respond to sounds, or rather does not respond in the ways that one might expect a person to. It is interesting that the rat pups are said to have an “autism-like condition” so soon after they are born—-while children are being diagnosed with autism at far younger ages, we have yet to hear of autism in a newborn.
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POSTED IN: Environment, Neuroscience, Science
7 opinions for PCBS and Newborn Rat Pups
María Luján Ferreira
Apr 25, 2007 at 5:40 pm
Hi Kristina
Exposure to PCBS has been linked to problems since birth
Am J Epidemiol. 2007 Apr 12
Prenatal Organophosphate Metabolite and Organochlorine Levels and Performance on the Brazelton Neonatal Behavioral Assessment Scale in a Multiethnic Pregnancy Cohort.Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS.
Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY.
Prenatal exposures to organophosphate pesticides and polychlorinated biphenyls have been associated with abnormal neonatal behavior and/or primitive reflexes. In 1998-2002, the Mount Sinai Children’s Environmental Health Center (New York City) investigated the effects of indoor pesticide use and exposure to polychlorinated biphenyls on pregnancy outcome and child neurodevelopment in an inner-city multiethnic cohort. The Brazelton Neonatal Behavioral Assessment Scale was administered before hospital discharge (n = 311). Maternal urine samples were analyzed for six dialkylphosphate metabolites and malathion dicarboxylic acid. A random subset of maternal peripheral blood samples from the entire cohort (n = 194) was analyzed for polychlorinated biphenyls and 1,1′-dichloro-2,2′-bis(4-chlorophenyl)ethylene. Malathion dicarboxylic acid levels above the limit of detection were associated with a 2.24-fold increase in the number of abnormal reflexes (95% confidence interval: 1.55, 3.24). Likewise, higher levels of total diethylphosphates and total dialkylphosphates were associated with an increase in abnormal reflexes, as was total dimethylphosphates after paraoxonase expression was considered. No adverse associations were found with polychlorinated biphenyl or 1,1′-dichloro-2,2′-bis(4-chlorophenyl)ethylene levels and any behavior. The authors uncovered additional evidence that prenatal levels of organophosphate pesticide metabolites are associated with anomalies in primitive reflexes, which are a critical marker of neurologic integrity.
Link
Consequences of prenatal toxin exposure for mental health in children and adolescents : A systematic review
Effects of Prenatal Exposure to Polychlorinated Biphenyls and Dioxins on Mental and Motor Development in Japanese Children at 6 Months of Age
J Med Invest. 2005 Feb;52(1-2):10-21. Links
Background exposure to PCDDs/PCDFs/PCBs and its potential health effects: a review of epidemiologic studies.Arisawa K, Takeda H, Mikasa H.
Department of Preventive Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Here we review epidemiologic studies dealing with the dietary intake and the body burden of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzo-furans (PCDFs)/ polychlorinated biphenyls (PCBs) in the general population, and potential adverse health effects of these substances, especially on the risk of diabetes mellitus and endometriosis, and on thyroid function and the neurodevelopment of infants. The mean or median intake of dioxin-related compounds among the general populations of various countries is lower than the maximum tolerable daily intake (TDI) set by the WHO in 1998 (4pg TEQ/kg/day). However, there have been few reports on the distribution of intake and the proportion of subjects whose exposure levels exceed the maximum TDL. At present, it remains unclear whether background exposure to dioxin-related compounds is associated with increased risk of diabetes (because of lack of longitudinal studies), endometriosis (because of lack of studies with sufficient statistical power), or altered thyroid function (because of inconsistent results on humans). Consistent results have been reported for the association between exposure to background levels of PCBs/dioxins, especially trans-placental PCBs, and defective neurodevelopment of infants in the U.S. and Europe. Thus, efforts should be made to further decrease the body burden among women of reproductive age by reducing the release of PCDDs/PCDFs/PCBs into the environment.
Am J Epidemiol. 2003 Mar 15;157(6):485-92.
Prenatal exposure to low-level polychlorinated biphenyls in relation to mental and motor development at 8 months.Daniels JL, Longnecker MP, Klebanoff MA, Gray KA, Brock JW, Zhou H, Chen Z, Needham LL.
Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Julie_Daniels@unc.edu
The relation between exposure to low levels of polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, and cognitive and motor development in young children has been examined in several studies, and results have varied. The authors evaluated the association between prenatal exposure to PCBs and children’s neurodevelopment using data from the Collaborative Perinatal Project. Pregnant women were enrolled from 1959 to 1965 from 12 sites across the United States. PCBs were measured in maternal serum taken during pregnancy. To measure children’s mental and psychomotor development at 8 months of age, the authors administered the Bayley Scales of Infant Development (means, 87 (standard deviation, 15) and 88 (standard deviation, 18), respectively). Overall, they did not observe a relation between prenatal PCB exposure and children’s mental or psychomotor scores (n = 1,207; multivariate adjusted beta = 0.1 point per micro g/liter increase of PCB, p = 0.71, and beta = 0.5, p = 0.14, respectively). The PCB-psychomotor score relation varied by study center (p Effects of PCB exposure on neuropsychological function in children
About autism from newborn, as you know the current idea is that there are differences since birth in the immunological and/or neurotrophins factors in autism (such as it has been published in levels of BDNF and other studies on blood of newborns that developed autism later).
Studies on prenatal exposure are being more and more published
J Pharmacol Exp Ther. 2007 Mar 30
Neuroinflammation and Behavioral Abnormalities after Neonatal Terbutaline Treatment in Rats: Implications for Autism.Zerrate MC, Pletnikov M, Connors SL, Vargas DL, Seidler FJ, Zimmerman AW, Slotkin TA, Pardo CA.
Johns Hopkins University School of Medicine.
Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills, and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2-5 or PN 11-14, and examined 24 hr after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2-5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11-14. In behavioral tests, animals treated with terbutaline on PN 2-5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.
Dev Med Child Neurol. 2006 Feb;48(2):84.
Autism and newborn encephalopathy.Fombonne E.
Lancet. 2006 Dec 16;368(9553):2167-78.
Developmental neurotoxicity of industrial chemicals.Grandjean P, Landrigan PJ.
Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are recognised causes of neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children. The two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the unique vulnerability of the developing brain are needed for testing and control of chemicals.
These are only some situations of the many reports with the implications of autism since birth. Including the infection with several viruses in pregnancy(rubella), the exposure to chemicals during pregnancy, the newborn encephalopaties and several other reported cases when during first year of life the development is very different of the considered typical ( and can be considered present since birth).
Please let me know if you are interested on other manuscripts on this topic.
chrisd
Apr 25, 2007 at 5:59 pm
I never thought about that. But there were things wrong early on; if it had been my second or third child I would have recognized it right away.
daedalus2u
Apr 25, 2007 at 9:24 pm
There is considerable data on the effects of PCBs on humans, and it doesn’t support an autism-PCB link. This review article discusses a number of quite tragic episodes.
One of the worst episodes was in Taiwan where children were exposed in utero to PCBs and (much worse) heat degraded PCBs. They found substantial problems, particularly in ectoderm differentiation (teeth, nails, hair). There was low birth weight, hyperpigmentation, teeth, acne (at birth). “The neurologists had an overall clinical impression of developmental or psychomotor delay in 12 (10%) of the exposed compared with 3 (3%) of the control children, and of a speech problem in 8 (7%) versus 3 (3%).”
The levels these children were exposed to were very high and the symptoms don’t match those of ASDs. PCBs have been banned since the 1970’s. They are very persistent, and do bioaccumulate. A connection to autism seems very unlikely.
Moi ;)
Apr 25, 2007 at 10:07 pm
Still, if you think about it….NJ…and its high rate….it’s enough of the “right kind of info” to make you double-take.
Kristina Chew, PhD
Apr 25, 2007 at 10:23 pm
Thanks María and Daedalu2 for all this information.
María Luján Ferreira
Apr 25, 2007 at 11:11 pm
Hi Kristina
Some very recent manuscript on the issue:
Chemosphere. 2007 Apr;67(9):S412-20.
Disrupting effects of hydroxy-polychlorinated biphenyl (PCB) congeners on neuronal development of cerebellar Purkinje cells: A possible causal factor for developmental brain disorders?
Kimura-Kuroda J, Nagata I, Kuroda Y.
Department of Brain Structure, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183-8526, Japan; CREST, Japan Science and Technology Agency, Saitama 330-0012, Japan.
Polychlorinated biphenyls (PCBs) and hydroxy-PCB (OH-PCB) metabolites are widely distributed bioaccumulative environmental chemicals and have similar chemical structures to those of thyroid hormones (THs). Previously, we reported that THs are essential for neuronal development and the low doses of two OH-PCBs, namely, 4-OH-2′,3,3′,4′,5′-pentachlorobiphenyl (4′-OH-PeCB-106) and 4-OH-2′,3,3′,4′,5,5′-hexachlorobiphenyl (4′-OH-HxCB-159), inhibited the TH-dependent dendritic development of Purkinje cells in mouse cerebellar cultures using serum-free defined medium. To determine which type of OH-PCBs affect neuronal development, we further examined several OH-PCBs and other estrogenic chemicals using this simple and sensitive assay system. Two-way ANOVA was used to assess the effects of OH-PCBs and other chemicals on both factors of their concentrations and with/without T4 in the assay of TH-dependent dendritic development of Purkinje cells. Aside from the two OH-PCBs, 4-OH-2′,3,4′,5,6′-pentachlorobiphenyl (4′-OH-PeCB-121) and bisphenol A significantly inhibited the TH-dependent dendritic development of Purkinje cells, whereas 4-OH-2′,3,3′,5′,6′-pentachlorobiphenyl (4′-OH-PeCB-112), 4-OH-2′,3,3′,5,5′,6′-hexachlorobiphenyl (4′-OH-HxCB-165), 4-OH-2,2′,3,4′,5,5′,6-heptachlorobiphenyl (4-OH-HpCB-187), progesterone and nonylphenol did not induce any inhibition, but significantly promoted the dendritic extension of Purkinje cells in the absence of THs. Other estrogenic chemicals, including beta-estradiol, diethyl stilbestrol and p-octylphenol did not show significant inhibitory or promoting effects. From these results, it is suggested that exposure to OH-PCBs and other environmental chemicals may disrupt normal neuronal development and cause some developmental brain disorders, such as LD, ADHD, and autism.
Paul Landers
May 25, 2007 at 12:19 am
Kristina Chew, PhD.
Please call me. I have an autistic son and potentially interesting information. Thanks.
(561) 963-0807
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