Dissertations / Theses on the topic 'Lead exposure; cognitive; development'
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McCabe, Marie E. "Lead Exposure, Attentional Outcomes, and Socioenvironmental Influences." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218548568.
Full textVollet, Martin Kaitlin A. "Pediatric Manganese Exposure and Cognitive Performance in Rural Appalachian Ohio." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1560867119903426.
Full textDonald, James M. "Chronic lead exposure : effects on behaviour and development in mice." Thesis, Glasgow Caledonian University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304102.
Full textTutunji, Maha Sa'di. "Development of analytical methods for the differential diagnosis of exposure to lead." Thesis, Loughborough University, 1988. https://dspace.lboro.ac.uk/2134/10511.
Full textBeckwith, Travis J. "A Magnetic Resonance Imaging Study of the Developmental Consequences of Childhood Lead Exposure in Adulthood." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439309120.
Full textMudge, Jane. "The effect of early exposure to environmental lead on the later development of girls and boys : a pilot study /." Adelaide, 1992. http://web4.library.adelaide.edu.au/theses/09ARPS/09arpsm944.pdf.
Full textFranklin, Milton. "A Case Study Investigation of the Impact of Early Aggression toward and Exposure to Violence on Children and Their Intellectual Development." Thesis, Saybrook University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10744227.
Full textThis study explored educators’ perceptions of the impact of exposure to violence on children and their intellectual development. Substitute concepts such as corporal punishment, child maltreatment, and others were considered relevant to formation of an individual’s identity. The study also explored the psychological impact of trauma over time, and its effect on an individual’s cognitive development, identity formation, and relational development. Various aspects of exposure to violence were examined, as questions arose regarding how these multiple forms of exposure to violence impact an individual’s level of functionality. This study utilized a general qualitative approach informed by case study methodologies.
Four educators who worked with children previously exposed to violence were interviewed. Although both teachers and tutors were solicited, only tutors responded to the invitation to participate; therefore, the results are based upon interviews with four tutors. Four specific themes emerged from the participant interviews, namely: the realities of children exposed to violence, the impact of violence, academic performance, and the role of the tutor. Within some themes, subthemes emerged such as emotional violence, physical violence, limited family support, the impact of violence, resiliency, combativeness, and lack of friendships. A narrative of themes and subthemes was presented. Commensurate with the focus of the research, the predominant theme identified in this research was that of violence and aggression on the part of adults, seen through the prism of the experiences of the children in their care.
Pershing, Michelle L. "Interactions Between Prenatal Kynurenic Acid Exposure and Adolescent Brain Development in the Emergence of Cognitive Deficits in Schizophrenia." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417275379.
Full textBasu, Amitabha Spotila James R. "Development of a 'genetic signature of environmental lead exposure' in wild Peromyscus using combinatorial data from cDNA microarrays and blood metabolites /." Philadelphia, Pa. : Drexel University, 2008. http://hdl.handle.net/1860/2796.
Full textToomer, Tarla TaMia. "Development of Risk Based Treatability and Engineering Measures for Reducing Exposure to Lead Contaminated Media in the Miami Inner City, Florida." FIU Digital Commons, 2008. http://digitalcommons.fiu.edu/etd/219.
Full textSiambani, Christine. "Maternal occupational exposure to organic solvents during pregnancy and subsequent visual and cognitive development in the child, a prospective controlled pilot study." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ50469.pdf.
Full textSoomro, Munawar Hussain. "Health effects of endocrine disruptors during pregnancy and childhood Exposure to heavy metals during pregnancy related to gestational diabetes mellitus in diabetes-free mothers Prenatal exposure to phthalates and the development of eczema phenotypes in male children: Results from the EDEN mother-child Cohort study." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS243.pdf.
Full textAll humans are exposed to chemicals in everyday life, from food, indoor environment, cosmetics and other products that surround us at home and at work. Endocrine disruptors (EDCs) are man-made compounds that can bind to cell receptors and mimic or block the functions of natural hormones potentially resulting in adverse health effects. In recent years, hypotheses have been put forward that EDCs may contribute also to the development of allergic and respiratory diseases. In addition, it is likely that EDCs could act already during pregnancy by causing gestational diabetes mellitus and pregnancy induced hypertension, which may also trigger to develop hypertension and diabetes mellitus later in life. This dissertation provides evidence that maternal exposure to phthalates and heavy metals (Lead, Cadmium and Manganese) during pregnancy may be associated with gestational diabetes mellitus, pregnancy induced hypertension and later eczema/atopic dermatitis in children. We used ongoing French EDEN-mother child cohort data for our three studies. Our results add new suggestive evidence on the relationship between EDCs (phthalates and heavy metals we studied) and maternal and children health, that prenatal exposure to certain phthalates and heavy toxic metals may play a role in the development of gestational diabetes mellitus and pregnancy induced hypertension during pregnancy and later eczema in early childhood. Future research focusing on larger populations and addressing multiple exposures assessed prenatally and postnatally are required to provide more evidence on possible contributions of emerging pollutants to study the role of phthalates and heavy metals
Rocha, Cláudio Felipe Kolling da. "Caracterização de um modelo animal de ambiente violento precoce com efeitos duradouros sobre o desenvolvimento." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/130559.
Full textViolence and aggressive behavior are part of human society from the begining. Although there are several public policies for violence control, it is still common and its consequences are present in modern society. Children raised in a violent environment have increased odds of developing psychopathology, like anxiety and depressive behavior, show decreased school performance and poor regulation of the hypothalamic-pituitary-adrenal axis. Mechanisms underlying those outcomes are complex and difficult to study in humans. Until present time, there are no animal models developed specifically for the study of early violent environment and its consequences. The aim of the present study was to develop and describe an animal model of early violent environment, with construct validity, face validity and predictive validity. We choose social stress during lactancy by the insertion of a male intruder in the dams home cage in the presence of its offspring as an intervention. A adult male rat was inserted for 5 minutes in dams home cage on post-natal days 3, 5, 7 and 9, during lights-on period. The outcomes assessed for face validity were Anxiety, stress response and cognitive performance. The outcomes assessed for predictive validity were maternal care variation and its impact on anxiety, cognitive performance and stress response regulation. The selected intervention had strong effects on the dams and offspring. Nursing behavior was decreased on the 30 minutes after each intervention. Violent environment dams displayed a shift in plasma corticosterone from the free to the bound fraction. Male pups showed decreased plasma corticosterone 30-40 minutes after the second intruder session, lasting throughout life. Male and female pups had increased juvenile anxiety. Male pups had increased anxiety, decreased cognitive performance and increased response to repeated psychological stress in adulthood. Maternal care quality was frequently associated with reduction better outcomes in the offspring. Maternal anxiety was found to be correlated to deleterious outcomes in the offspring. The intervention proved to be a consistent model of early violent environment, showing strong construct validity, face validity and predictive validity.
Rioux, Camille. "Feeding the mind : the development of food categories and its association with food neophobia and pickiness in young children." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0351/document.
Full textFood neophobia and pickiness in young children are two strong barriers to fruit and vegetable consumption. It is therefore essential to understand the mechanisms underpinning these two kinds of food rejections to promote the adoption of healthy eating behaviors among preschoolers. In this context, the first objective of the thesis was to develop a hetero-assessment scale to measure efficiently food neophobia and pickiness for French children as young as 2 years of age. The scale developed represents an efficient tool for studying food rejection dispositions in this young population. The second objective was to clarify the concept of pickiness and to provide an insight into the relationship between food neophobia and pickiness. The results revealed that food neophobia and pickiness capture a same kind of fear for new and potentially toxic food. The third objective was to directly investigate the relationship between food categorization development in young children and their food neophobia and pickiness. The thesis is one of the first studies to investigate directly this relationship.This investigation revealed negative connections between cognitive development and food rejection dispositions. Food acceptance probably depends on the maturity of the food categorization system. Finally, the fourth objective was to design an intervention, exploiting the empirical evidence on the relationship between food categorization and food rejections, to positively influence children food rejections. The results add to the promising body of evidence that visual exposure is effective to decrease food rejection behaviors
Earl, Rachel. "An investigation of the effects of lead on children’s cognitive abilities." Thesis, 2011. http://hdl.handle.net/2440/71322.
Full textThesis (Ph.D.) -- University of Adelaide, School of Psychology, 2011
Tsai, Yu-Chen, and 蔡鈺晨. "Detrimental Effect of Lead Exposure on Molar Development in Rat Fetuses." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/44634748892200664477.
Full text高雄醫學大學
牙醫學研究所
99
Objective: This study evaluates effects of maternal exposure to different dose and time of lead on tooth development in rats fetuses. Materials &Methods: Pregnant rats were randomly divided into five groups: groups I was given deionized water, groups II and III drank lead acetate water in dose of 50 and 200 mg/L respectively throughout gestation, groups IV and V drank lead acetate water in dose of 50 and 200 mg/L respectively throughout lactation. Rat fetuses were sacrificed at 35 days postnatally and first molar were collected for morphometric studies. Results: No abnormalities in cusp number, form were noticed in the experimental groups. Many deep and longitudinal groves was noticed near enamo-dentinal junction on the molar surface. Analysis with ANOVA indicated a statically significant difference in linear measurement of crown size (P<0.0001). Further analysis revealed that the mesiodistal and buccolingual diameters were significantly smaller in lactation groups. Both bone morphogenetic protein-4 and fibroblast growth factor were immunohistochemical staining in stellate reticulum and ameloblast zone in the gestation groups and lactation groups. No differences were found in immunostaining intensity between the experimental groups and control groups. Conclusions: The administration of lead during gestation and lacation period cause adverse effect on molar size in the laboratory rat.
Shvachiy, Liana. "Comparative study on the physiological dynamics evoked by different profiles of lead exposure." Master's thesis, 2018. http://hdl.handle.net/10451/37849.
Full textLead is a toxic metal which widespread use has resulted in environmental contamination and significant health problems. It is a cumulative toxicant that affects multiple body systems, including the cardiovascular, hematopoietic, reproductive, and renal systems. Lead is also a well-known neurotoxin, inducing changes in neurogenesis, neurodegeneration and changes on glial cells. These changes in the molecular and cellular processes lead to cognitive and behaviour alterations, particularly during developmental phases, persisting throughout the lifetime. Most of the studies that have been performed in both humans and animals were focused in a continuous chronic exposure to lead. This lead exposure causes behavioural changes, cognitive impairment and hypertension associated with sympathoexcitation, baroreceptor reflex hyposensitivity and increased chemoreceptor reflex sensitivity. But the effects of an intermittent lead exposure are scarse and standardized animal models are non-existent. This pattern of exposure has been increasing in the last years due to migrations, implementation of school exchange programs and/or residential changes. Therefore, the overall purpose of this work was to evaluate lead effects on mammal’s physiology along different profiles of lead exposure, including a new animal model of intermittent low-level lead exposure. Animal models of lead exposure were developed by replacing the tap water of seven-day pregnant Wistar females with 0.2% (p/v) solution of lead acetate. After being weaned at 21 days, rat pups, both sexes, were divided into 3 groups of lead exposure: long-term (exposure from foetal period until 28 weeks of age), short-term (exposure from foetal period until 12 weeks) and intermittent (exposure from foetal period until 12 weeks, lead-free period until 20 weeks and a second exposure between 20 and 28 weeks of age). At 12, 20 and 28 weeks of age, behavioural tests were performed for anxiety (Elevated Plus Maze Test), locomotor activity (Open Field Test), spatial working memory (Y-Maze) and episodic long-term memory (Novel Object Recognition test) assessment. Blood pressure (BP), electrocardiogram (ECG), heart rate (HR) and respiratory frequency (RF) were recorded at the same timepoints in the acute experiment. Baroreflex gain (BRG), chemoreflex sensitivity (ChS), cardiovascular variability were also evaluated. Immunohistochemistry studies for neuronal nuclear antigen (NeuN), Synaptophysin (Syn), ionized calcium binding adapter molecule-1 (Iba-1) and Glial fibrillary acidic protein (GFAP) stainings were performed in brain slices, and confocal imaging acquired and stainings quantified at dentate gyrus (DG) of the hippocampus. Blood lead levels were assessed by atomic absorption spectroscopy and metabolic evaluation of all groups was done using metabolic cages. A control group of Wistar rats without lead exposure, of both sexes, with the same number of individuals, underwent the same protocol and were evaluated in the same time points. Student T-test and one-way ANOVA with Tukey’s multiple comparison between means were used (significance p<0.05) for statistical analysis. Our data showed a clear association between lead exposure, hypertension and cardiorespiratory reflexes impairment, without heart rate changes, independently of the type of lead exposure profile. We also demonstrated for the first time that lead intermittent exposure causes adverse health effects, i.e, hypertension, sympathetic overactivity, increased chemoreflex sensitivity and baroreflex impairment, similar to a chronic exposure, however less pronounced. In fact, at 28 weeks, PbI group, the intermittent animal model of lead exposure developed, had a less severe hypertension when compared to the long-term exposure group (PbP), which might suggest that the duration of Pb exposure is more relevant than the time of exposure. Moreover, the effect on diastolic blood pressure produced by lead exposure was more evident than that of systolic blood pressure. Lead exposure from foetal period until 12 weeks of age causes long lasting hypertension and chemoreceptor reflex dysfunction even after a 16 weeks period without exposure. However, the clearance of lead promoted an improvement in baroreceptor reflex function, with repercussions on blood pressure values, since these values decreased, but did not reached the normotensive values. Regarding the autonomic data, in our study, the overactivity of the sympathetic nervous system, evaluated by the LF band, is concomitant with baroreceptor reflex impairment and/or hypertension. This means that the sympathetic nervous system may be involved in the modulation of the baroreceptor reflexes responses or in the hypertension development due to lead exposure. Concerning the effect of lead at behavioural level, all groups exposed to lead, evaluated in the three different time points, had behavioural changes, namely anxiety, hyperactivity and/or long-term memory impairment and molecular changes in the hippocampus region, more specifically, reactive astrogliosis and microgliosis were detected, indicating the presence of neuroinflammation. However, these alterations seem to reverse after lead abstinence for a certain period (single exposure) and are enhanced when a second exposure occurs (intermittent exposure), along with a synaptic loss. In summary, this study shows, that exposure to lead during the developmental phase can alter the normal course of development, with lifelong health consequences. Since all exposed Pb groups had the same route of exposure (i.e. exposure to lead by water) and the same dose and, despite the different time of exposure, all were exposed to lead since foetal period until adulthood, the most susceptible period to adverse health effects. Therefore, we can conclude that the different effects of lead toxicant between groups mainly depends on the total duration of lead exposure. This comparative study brings new insights on the environmental factors that influence nervous and cardiovascular systems during development, which can help creating public policy strategies to prevent and control the adverse effects of Pb toxicity.
A identificação de agentes potencialmente tóxicos e a avaliação dos seus efeitos sobre o organismo humano constituem um tema importante de saúde pública. O chumbo encontra-se neste grupo de agentes, sendo bastante utilizado em todo o mundo, devido às suas propriedades únicas, como a alta maleabilidade, baixo ponto de fusão, suavidade, ductilidade e resistência à corrosão. O vasto uso deste metal pesado em indústrias, como a automóvel, cerâmica, de tintas e do plástico levou ao aumento da quantidade de chumbo livre no ambiente e a sua ocorrência nos sistemas biológicos, devido à sua natureza não biodegradável. A toxicidade do chumbo, como resultado da sua ingestão, inalação ou por contacto direto, mesmo em pequenas quantidades, pode evocar efeitos adversos irreversíveis em várias funções do corpo, afetando principalmente os sistemas cardiovascular (sendo uma das causas da hipertensão, promovendo aterosclerose, trombose, arteriosclerose e doenças cardiovasculares), hematopoiético, reprodutivo e renal. O chumbo é também uma neurotoxina já bem estudada, que induz alterações na neurogénese, nas células gliais e neurodegeneração. Estas alterações nos mecanismos celulares e moleculares, quando ocorrem durante as fases de desenvolvimento, provocam alterações cognitivas e comportamentais, que persistem durante toda a vida. Em termos de classificação, dois tipos de toxicidade de chumbo podem ser definidos: a toxicidade aguda, que geralmente ocorre pela exposição ocupacional a níveis elevados de chumbo, sendo esta bastante incomum, e a toxicidade crónica, uma exposição a níveis baixos de chumbo, mais comum no ambiente familiar. A maioria dos estudos realizados até à data em seres humanos e animais, focam-se na exposição crónica contínua e/ou permanente ao chumbo e nas consequências adversas na saúde deste tipo de exposição. Existem já, vários modelos animais descritos para a exposição contínua a níveis baixos de chumbo. No entanto, em determinadas situações, como nas migrações, nos programas de intercâmbio escolar e/ou nas mudanças residenciais, a exposição intermitente ao chumbo pode ocorrer, mas os estudos disponíveis em seres humanos são escassos e os modelos animais padronizados inexistentes para este tipo de exposição, que tem vindo a crescer exponencialmente nos últimos anos. Posto isto, o objetivo geral deste trabalho consistiu em avaliar os efeitos de diferentes perfis de exposição a níveis baixos de chumbo na fisiologia de ratos Wistar, incluindo o desenvolvimento de um novo modelo animal de exposição intermitente a chumbo. Os modelos animais de exposição ao chumbo foram desenvolvidos substituindo a água dos biberões das fêmeas Wistar grávidas de sete dias por uma solução de acetato de chumbo a 0,2% (p/v). Após os 21 dias de desmame, as crias, de ambos sexos, foram divididas em 3 grupos de exposição ao chumbo: de longo prazo (PbP - exposição do período fetal até às 28 semanas de idade), de curto prazo (Short-term PbS - exposição do período fetal até às 12 semanas, com abstinência ao chumbo até às 28 semanas) e intermitente (PbI - exposição do período fetal até 12 semanas, seguida por um período sem chumbo até 20 semanas e uma segunda exposição entre 20 e 28 semanas de idade). Em três diferentes pontos temporais (12, 20 e 28 semanas de idade), os diferentes grupos de animais foram sujeitos a testes comportamentais, para a avaliação dos níveis de ansiedade (EPM), da atividade locomotora (OFT), da memória espacial de trabalho (Y-Maze) e da memória episódica de longo prazo (NOR). Para avaliação dos parâmetros fisiológicos nos diferentes pontos temporais, os animais foram sujeitos a uma experiência aguda, onde foram registados os seguintes parâmetros: pressão arterial (PA), eletrocardiograma (ECG), frequência cardíaca (FC) e frequência respiratória (FR). Nesta experiência também se avaliaram os reflexos baro- e quimiorrecetores e obtiveram-se registos para a análise da variabilidade da FC e da PA sistólica. Após o término da experiência aguda, os animais foram sacrificados e os cérebros extraídos para estudos de imunohistoquímica em secções coronais, nas quais se analisou a morfologia das células e se quantificou a perda neuronal (neuronal nuclear antigen - NeuN), a astrogliose (Glial fibrillary acidic protein – GFAP) e a microgliose (ionized calcium binding adapter molecule-1 - Iba-1), bem como alterações na transmissão sináptica (Synaptophysin – Syn) no girus dentado do hipocampo. Os níveis de chumbo no sangue foram avaliados por espectroscopia de absorção atómica e a avaliação metabólica realizada através do uso de gaiolas metabólicas. Um grupo controlo de ratos Wistar sem exposição ao chumbo, de ambos os sexos e com o mesmo número de indivíduos, foi submetido ao mesmo protocolo e foi avaliado nos mesmos pontos temporais (12, 20 e 28 semanas de idade). Para a análise estatística foi utilizado o teste T de Student e a análise de Variância (ANOVA) unidirecional com o teste post-hoc de Tukey, considerando-se significativas diferenças com p < 0,05. Os resultados deste estudo mostram que, independentemente do tipo de perfil de exposição ao chumbo, existe uma associação clara entre exposição a chumbo, hipertensão e diminuição do ganho do barorreflexo, sem alterações de frequência cardíaca. Também demonstramos, pela primeira vez, que uma exposição intermitente a chumbo provoca efeitos adversos para a saúde, como hipertensão, hiperatividade simpática, aumento da sensibilidade quimiorreflexa e diminuição do ganho do barorreflexo, efeitos adversos semelhantes ao de uma exposição crónica permanente (PbP), porém menos pronunciada. De facto, às 28 semanas, o grupo PbI, o modelo animal intermitente de exposição ao chumbo desenvolvido, apresentou uma hipertensão menos grave em relação ao grupo de exposição de longo prazo (PbP), o que pode sugerir que a duração da exposição ao chumbo é mais relevante do que o tempo de exposição. Além disso, o efeito da exposição ao chumbo sobre a pressão arterial diastólica foi mais evidente do que sobre a pressão arterial sistólica. A exposição ao chumbo, desde o período fetal até as 12 semanas de idade, provoca hipertensão e disfunção quimiorreflexa duradoura, mesmo com um período de 16 semanas sem exposição. No entanto, a abstinência do chumbo promoveu uma melhoria na função barorreflexa, com repercussões nos valores da pressão arterial, uma vez que estes valores diminuíram, apesar de não atingirem os valores de normotensão. Em relação à avaliação autonómica, os dados indicam que quando existe um aumento do tónus simpático, avaliado pela banda LF, este é concomitante com disfunção barorreflexa e/ou hipertensão arterial. Isso significa que o sistema nervoso simpático deve estar envolvido na modulação da resposta barorreflexa ou no desenvolvimento da hipertensão decorrente da exposição ao chumbo. Relativamente ao efeito do chumbo a nível comportamental, todos os grupos expostos ao chumbo, avaliados nos diferentes pontos temporais, apresentaram alterações comportamentais, nomeadamente ansiedade, hiperatividade e / ou défices de memória a longo prazo, bem como alterações moleculares, mais especificamente, astrogliose e microgliose reativa, que indicam a presença de neuroinflamação. No entanto, estas alterações parecem reverter após a abstinência do chumbo durante um determinado período (PbS - exposição de curta duração), sendo mais evidentes quando ocorre uma segunda exposição a chumbo (PbI - exposição intermitente), levando mesmo a perda sináptica mais pronunciada. Em resumo, este estudo mostra, que exposições a chumbo durante as fases de desenvolvimento podem alterar o seu curso normal, com consequências adversas para a saúde que podem persistir para toda a vida. Uma vez que todos os grupos expostos a chumbo tiveram a mesma via de exposição (isto é, exposição ao chumbo através da água) e a mesma dose e, apesar do tempo de exposição diferente, todos foram expostos ao chumbo desde o período fetal até a idade adulta, período em que são mais suscetíveis a efeitos adversos na saúde. Portanto, podemos concluir que os diferentes efeitos tóxicos do chumbo entre os grupos dependem principalmente da duração total da exposição ao chumbo. As novas evidências obtidas por este estudo comparativo permitem-nos contribuir para o esclarecimento sobre os fatores ambientais que influenciam os sistemas nervoso e cardiovascular durante o desenvolvimento, o que pode ajudar a criar estratégias de políticas públicas para prevenir e controlar os efeitos adversos da toxicidade do chumbo.
Van, Vuuren Jacqueline. "The cognitive processing potential of infants: a study of the effect of early infant exposure to numbers, shapes and colours." Diss., 2014. http://hdl.handle.net/10500/14615.
Full textPsychology
M.A. (Psychology)
Yang, Tzu-Hsuan, and 楊子萱. "The relationship between prenatal and postnatal mercury/methylmercury exposure and their cognitive, language and motor development at three years old." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/63892983780010136660.
Full textWagner, Jennifer Lynne. "Effects of coadministration of D-Napvsipq [NAP] and D-Sallrsipa [SAL] on spatial learning after developmental alcohol exposure." Thesis, 2013. http://hdl.handle.net/1805/5066.
Full textDespite warnings about the dangers of drinking during pregnancy, little progress has been made in reducing alcohol drinking among women of childbearing age. Even after the recognition of pregnancy, 15% of women continue to drink, 3% of which admit to binge drinking. Because we cannot stop women from drinking during pregnancy, and many children with fetal alcohol spectrum disorders (FASD) are adopted, there is a significant need to develop postnatal interventions that can improve the long-term outcome of children adversely affected by prenatal alcohol exposure. This thesis aims to evaluate one promising new treatment in the rehabilitation or rescue of specific learning deficits long after the damage has occurred. The treatment evaluated herein (40µg D-NAP + 40µg D-SAL) has long been used in the prevention of the detrimental effects of long-term and binge-like alcohol exposures in rodent models of fetal alcohol syndrome and FASD. Until recently this peptide treatment had only been shown to be effective in preventing some of the consequences of alcohol exposure when administered concurrently with the prenatal alcohol exposure. A recent report by Incerti and colleagues (2010c), however, reported that these peptides could completely reverse a profound spatial learning deficit induced by one episode of a heavy binge-like alcohol exposure (5.9g.kg in a single intraperitoneal injection) on gestational day 8 (G8) in C57BL/6 mice. In that report, the peptide treatment was administered starting in late adolescence, beginning three days prior to and throughout water maze training, and the profound deficits in their alcohol-placebo group were completely eliminated in the alcohol-peptide group. There are currently no FDA-approved treatments for FASD. An effective treatment for the cognitive and behavioral dysfunctions suffered by the 1% of people born today could potentially improve the lives of millions of children and adults. The first aim of this thesis was to determine whether the peptide treatment could reverse the significant spatial learning deficits we have demonstrated in adult C57BL/6 mice given high-dose binge-like alcohol exposure (2.5 g/kg in each of two intraperitoneal injections separated by two hours) on postnatal day (P)7. When administered three days prior to and throughout water maze testing (P67-76), the peptide treatment had no effect on spatial learning. The second aim sought to determine whether the same peptide treatment could reverse water maze spatial learning deficits in G8 binge-like exposure models, as reported by Incerti et al. (2010c). For this analysis, the first study used a different binge-like alcohol exposure model that is more commonly used than that employed by the Incerti et al. (2010c) study, namely administration of 2.8g/kg in each of two intraperitoneal injections separated by four hours (Sulik et al., 1981). This model has been shown to produce high peak blood alcohol concentrations and neuroanatomical aberrations in the hippocampal formation and septal regions (Parnell et al., 2009), which have been implicated in learning and memory. Surprisingly, this G8 binge-like alcohol exposure failed to produce a spatial learning deficit, undermining the usefulness of this model in evaluating the peptide effects. In direct contrast to the outcomes of Incerti et al. (2010c), the G8 Webster alcohol exposure was also unable to produce any deficits in acquisition of spatial learning in the Morris water maze. Surprisingly, neither of the heavy binge-like alcohol exposures on G8 were able to produce spatial learning deficits in the Morris water maze. The binge-like alcohol exposure on P7 did yield the expected spatial learning deficit, but the peptide treatment was unsuccessful in recovering water maze learning. These findings fail to support oral administration of 40µg D-NAP and 40 µg D-SAL as a potential therapy for postnatal alcohol-induced spatial learning deficits in adult mice.