Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in Fetal Alcohol Spectrum Disorders (FASD). Recently, we showed that third trimester alcohol exposure lead to a persistent disruption in ocular dominance (OD) plasticity. For instance, few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors such as the cAMP response element binding protein (CREB) and the Serum response factor (SRF). SRF is important for many plasticity processes such as LTP, LTD, spine motility and axonal pathfinding. Here we attempt to rescue OD plasticity in alcohol-treated ferrets using a Sindbis viral vector to express a constitutively active form of SRF during the period of monocular deprivation. Using optical imaging of intrinsic signals and single unit recordings we observed that overexpression of a constitutively active form of SRF (Sindbis SRF+), but neither its dominant negative (SRF-) nor GFP, restored OD plasticity in alcohol-treated animals. Surprisingly, this restoration was observed throughout the extent of the primary visual cortex and most cells infected by the virus were positive for GFAP rather than NeuN. Hence, we further tested whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to the SRF+, SRF- or control GFP viruses. After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF- or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD.

The thesis devotes to the negative effects of alcohol abuse during pregnancy on early psychical development of the child. It surveys the problematic fields of development of the children who were prenatally exposed to alcohol. The theoretical survey is accompanied by qualitative empirical part, which contains four case studies of children in the age of 6 - 72 weeks whose mothers were drinking alcohol during pregnancy. There are several problematic areas in the development of these children, for example growth deficit, retardation of the psychomotor development (especially in speech, gross motor skills and social behaviour), attachment disorders and eating disorders. These signs correspond to the scientific literature, but there are differences in the extent and frequency in the children Key words: alcohol, fetal alcohol syndrome, fetal alcohol spectrum disorders, early psychomotor development

Introdução: O consumo de bebidas alcoólicas por gestantes acarreta alterações de formação e de desenvolvimento fetal, incluindo alterações estruturais e funcionais do Sistema Nervoso Central. Os comprometimentos sensoriais de crianças expostas ao álcool na gestação, como a audição, são uma das morbidades relatadas nesta população. A ocorrência de alteração da sensitividade auditiva é melhor conhecida, mas o envolvimento do sistema nervosos auditivo central ainda carece de pesquisas. Objetivo: Estudar a função auditiva, periférica e central, em crianças em idade escolar com expostas ao álcool no período pré-natal. Métodos: Foram avaliadas 45 crianças, de ambos os gêneros, com 13 e 14 anos, provenientes do projeto INFANTO-ÁLCOOL, divididas em grupo exposto (GE) e não exposto (GNE) ao álcool na gestão. Foram realizadas audiometria tonal limiar, imitânciometria, emissões otoacústicas transientes (EOA-T), potencial evocado auditivo de tronco encefálico (PEATE) e o potencial evocado auditivo tardio, potencial evocado auditivo de longa latência (PEALL) e relacionado a eventos (PEARE), registrado em Cz e Pz. Foi realizada a análise comparativa entre grupos. Resultados: Apenas uma criança do GE apresentou perda auditiva unilateral do tipo mista, sendo os demais com limiares auditivos dentro da normalidade, com predominância de curva timpanomética do tipo \"A\" e presença de reflexo contralateral. Quanto ao funcionamento coclear e avaliação comportamental do processamento auditivo, não houve diferença entre grupos. Embora os resultados do PEATE tenham sido sugestivos de alteração na sincronia neural em nível de tronco encefálico, a diferença entre grupos não foi apontada. Para o PEALL, o GE apresentou menor amplitude de P2, na derivação Pz; no PEARE maiores amplitudes de P3a foram evidenciadas no GE, em Cz. Na comparação entre os eletrodos ativos foi possível constatar maior identificação da P3 com duplo pico para o eletrodo em Pz. Conclusão: O perfil de exposição fetal ao álcool em qualquer trimestre gestacional, esteve relacionado a alteração na sincronia neural em nível de tronco encefálico, bem como na identificação das componentes P2 e P3a. / Introduction: The consumption of alcohol by pregnant women causes abnormalities on fetal growth and development, including structural and functional changes in the Central Nervous System. The sensory impairments of children exposed to alcohol during pregnancy, such as hearing, are one of the morbidities reported in this population. The occurrence of change in hearing sensitivity is better known, but the auditory central nervous system involvement still needs more research. Objective: To study the hearing function, peripheral and central, in school-age children with exposed to alcohol prenatally. Methods: 45 children were assessed, of both genders, in age of 13 and 14 years, from INFANTO-ÁLCOOL project, allocated in two groups, exposed (EG) and not exposed (NEG) to alcohol during pregnancy. Following tests were performed: - pure tone audiometry, acoustic immittance, transient otoacoustic emissions (TOEA), brainstem auditory responses (ABR), late auditory evoked potentials, longlatency auditory evoked potential (LLAEP) and event-related (ERAP), registered in Cz and Pz, with comparative analysis between groups. Results: Only one child of EG had a unilateral mixed hearing loss, being the others participants found in the normal hearing thresholds, with predominance of timpanometric curve of type \"A\" and presence of contralateral acoustic reflex. Regarding the cochlear function and behavioral auditory processing assessment, there were no differences between groups. Although, the ABR results have been suggestive of change in neural synchrony brainstem level, the difference between groups was not confirmed. For the LLAEP, the EG showed lower amplitude of P2, in Pz deriving electrode; to the EARP P3a component had larger amplitudes in EG, in Cz. The comparison between the active electrode was possible to record a greater identification of the P3 components with double peak for the electrode in Pz. Conclusion: The profile of fetal exposure to alcohol in any trimester dates was related to change in neural synchrony in brainstem level as well as in the identification of P2 and P3a components.

Introdução: O consumo de bebidas alcoólicas por gestantes acarreta alterações de formação e de desenvolvimento fetal, incluindo alterações estruturais e funcionais do Sistema Nervoso Central. Os comprometimentos sensoriais de crianças expostas ao álcool na gestação, como a audição, são uma das morbidades relatadas nesta população. A ocorrência de alteração da sensitividade auditiva é melhor conhecida, mas o envolvimento do sistema nervosos auditivo central ainda carece de pesquisas. Objetivo: Estudar a função auditiva, periférica e central, em crianças em idade escolar com expostas ao álcool no período pré-natal. Métodos: Foram avaliadas 45 crianças, de ambos os gêneros, com 13 e 14 anos, provenientes do projeto INFANTO-ÁLCOOL, divididas em grupo exposto (GE) e não exposto (GNE) ao álcool na gestão. Foram realizadas audiometria tonal limiar, imitânciometria, emissões otoacústicas transientes (EOA-T), potencial evocado auditivo de tronco encefálico (PEATE) e o potencial evocado auditivo tardio, potencial evocado auditivo de longa latência (PEALL) e relacionado a eventos (PEARE), registrado em Cz e Pz. Foi realizada a análise comparativa entre grupos. Resultados: Apenas uma criança do GE apresentou perda auditiva unilateral do tipo mista, sendo os demais com limiares auditivos dentro da normalidade, com predominância de curva timpanomética do tipo \"A\" e presença de reflexo contralateral. Quanto ao funcionamento coclear e avaliação comportamental do processamento auditivo, não houve diferença entre grupos. Embora os resultados do PEATE tenham sido sugestivos de alteração na sincronia neural em nível de tronco encefálico, a diferença entre grupos não foi apontada. Para o PEALL, o GE apresentou menor amplitude de P2, na derivação Pz; no PEARE maiores amplitudes de P3a foram evidenciadas no GE, em Cz. Na comparação entre os eletrodos ativos foi possível constatar maior identificação da P3 com duplo pico para o eletrodo em Pz. Conclusão: O perfil de exposição fetal ao álcool em qualquer trimestre gestacional, esteve relacionado a alteração na sincronia neural em nível de tronco encefálico, bem como na identificação das componentes P2 e P3a. / Introduction: The consumption of alcohol by pregnant women causes abnormalities on fetal growth and development, including structural and functional changes in the Central Nervous System. The sensory impairments of children exposed to alcohol during pregnancy, such as hearing, are one of the morbidities reported in this population. The occurrence of change in hearing sensitivity is better known, but the auditory central nervous system involvement still needs more research. Objective: To study the hearing function, peripheral and central, in school-age children with exposed to alcohol prenatally. Methods: 45 children were assessed, of both genders, in age of 13 and 14 years, from INFANTO-ÁLCOOL project, allocated in two groups, exposed (EG) and not exposed (NEG) to alcohol during pregnancy. Following tests were performed: - pure tone audiometry, acoustic immittance, transient otoacoustic emissions (TOEA), brainstem auditory responses (ABR), late auditory evoked potentials, longlatency auditory evoked potential (LLAEP) and event-related (ERAP), registered in Cz and Pz, with comparative analysis between groups. Results: Only one child of EG had a unilateral mixed hearing loss, being the others participants found in the normal hearing thresholds, with predominance of timpanometric curve of type \"A\" and presence of contralateral acoustic reflex. Regarding the cochlear function and behavioral auditory processing assessment, there were no differences between groups. Although, the ABR results have been suggestive of change in neural synchrony brainstem level, the difference between groups was not confirmed. For the LLAEP, the EG showed lower amplitude of P2, in Pz deriving electrode; to the EARP P3a component had larger amplitudes in EG, in Cz. The comparison between the active electrode was possible to record a greater identification of the P3 components with double peak for the electrode in Pz. Conclusion: The profile of fetal exposure to alcohol in any trimester dates was related to change in neural synchrony in brainstem level as well as in the identification of P2 and P3a components.

No description available.

[pt] O consumo de álcool durante gravidez pode alterar o desenvolvimento neural do feto, causando defeitos ao longo da vida. As consequências são diversas e compõe o termo coletivo: Transtorno do Espectro Alcoólico Fetal (TEAF). Esse transtorno é considerado a causa mais comum de deficiência cognitiva evitável no mundo. Estimativas apontam que no Brasil entre 1 e 1,5% das crianças nascem com alterações no sistema nervoso devido à exposição ao álcool in útero. O consumo do álcool é frequente entre mulheres grávidas muitas vezes por desconhecimento dos seus efeitos adversos no desenvolvimento do feto. Outra droga comumente utilizada por mulheres grávidas é a maconha com intuito de amenizar o enjoo durante a gestação. A presente dissertação explora os efeitos da exposição pré-natal ao álcool no feto (em conjunto ou não do uso da maconha) em estudos pré-clínicos e clínicos. Dois artigos foram gerados para a realização deste trabalho. O primeiro artigo relata os mecanismos e as consequências do consumo simultâneo de álcool e maconha durante gravidez, cujo efeito é ainda mais nocivo ao desenvolvimento do feto do que apenas a exposição ao álcool. Dados recentes demonstram a interação do etanol e da maconha com o sistema Endocanabinoide, que tem um papel importante no neurodesenvolvimento. Depois do fechamento do tubo neural, que acontece durante a terceira semana da gestação humana, os olhos e o cérebro se desenvolvem do neuroepitélio. Ambos, o álcool e maconha interferem sinergicamente nesse processo via receptores canabinóides, alterando assim a sinalização “sonichedgehog”, que por sua vez, resulta em alterações morfológicas e comportamentais em modelos animais. Além disso, o artigo relata os mais recentes achados de estudos clínicos sobre a combinação da dose e tipo de constituintes químicos da machonha, bem como os desfechos morfológicos e neurocomportamentais da exposição conjunta do álcool e da maconha. O segundo artigo é uma revisão sistemática que investiga as pesquisas realizadas no Brasil sobre o TEAF, com ênfase nos instrumentos usados para a avaliação neuropsicológica de indivíduos com TEAF. Enquanto países desenvolvidos têm décadas de pesquisa sobre o TEAF, no Brasil, inúmeros fatores comprometem o progresso nesta e outras áreas de pesquisa. Entre esses fatores podemos citar, divergências socioeconômicas, culturais e geopolíticas, que dificultam o desenvolvimento, adaptação e validação de instrumentos utilizados no diagnóstico e na avaliação neuropsicológica do TEAF. Além disso, vale ressaltar que a vulnerabilidade socioeconômica da população brasileira é um fator importante no aumento da ocorrência de formas mais graves de TEAF. A revisão sistemática aponta para a necessidade da validação das ferramentas neuropsicológicas de diagnóstico e avaliação cognitiva de pessoas com TEAF e da participação de uma equipe multidisciplinar no diagnóstico do TEAF. / [en] Alcohol consumption during pregnancy may damage the development of the fetus, resulting in the most common preventable cause of neurodevelopmental disability in the world: Fetal Alcohol Spectrum Disorders (FASD). The present dissertation aims to discuss the effects of alcohol on the developing CNS through two articles. The first article elucidates the mechanisms and outcomes of the combined alcohol and cannabis exposure in the offspring through preclinical studies. Alcohol teratogenesis is more potent when administered with cannabis and has more negative effects on the fetus than alcohol alone. Recent data demonstrate the interaction of ethanol and cannabis with the Endocannabinoid system, which plays an important role in neurodevelopment and explains the morphological and behavioral changes seen in preclinical studies. The second article is a systematic review that investigates Brazilian research on FASD, focusing on the instruments used for the neuropsychological assessment of individuals with FASD. While developed countries have decades of research on FASD, in Brazil numerous factors slow down the progress of in this and other areas of research. Socioeconomic status, cultural, and geopolitical divergences are some of these factors, which hinder the development, adaptation, and validation of instruments used in the diagnosis and neuropsychological assessment of FASD. In addition, it is worth noting that the socioeconomic vulnerability of the Brazilian population is an important factor in the increase in the occurrence of more severe forms of FASD. The systematic review points to the need to validate neuropsychological tools for the diagnosis and cognitive assessment of individuals with FASD in Brazil, and the participation of a multidisciplinary team in the diagnosis of FASD.

No description available.

Hierdie studie het op die gevolge van gebrekkige ouerbetrokkenheid by leerders met fetale alkoholsindroom (FAS), soos ervaar deur onderwysers in die Wes-Kaap, gefokus. Daar is gebruik gemaak van ’n kwalitatiewe navorsingsproses waar nege in-diepte onderhoude met onderwysers gevoer is. Die onderwysers is gevra om hulle geleefde ervaringe te deel oor die gevolge van gebrekkige ouerbetrokkenheid asook die faktore wat ouers verhoed om aktief betrokke te raak by die opvoeding, dissiplinering en ondersteuning van hulle kinders met FAS. Die navorser wou juis onderwysers se ervaringe ondersoek, aangesien hulle bewus is van die gevolge van gebrekkige ouerbetrokkenheid en die invloed wat dit op ’n leerling met FAS mag hê. Geen navorsing wat spesifiek konsentreer op onderwysers se ervaringe van die gevolge van gebrekkige ouerbetrokkenheid in die Wes-Kaap is tans beskikbaar nie. Die voorkoms en voorkoming van fetale alkoholsindroom is ’n onderwerp wat nou baie aandag ontvang, alhoewel navorsing tot op hede selde op die betrokkenheid van ouers en die negatiewe gevolge van onbetrokke ouers op FAS leerders gefokus het. Die studie poog ook om lig te werp op die unieke uitdagings wat leerders met FAS ten opsigte van dissipline openbaar, asook onderwysers se ervaringe van leerders met FAS. Die invloed wat gebrekkige ouerbetrokkenheid op ’n leerder met FAS se gedrag en selfs die leerder se toekoms mag hê, word ook ondersoek. / This research project was done to determine what the consequences are for children with foetal alcohol syndrome (FAS) when their parents are uninvolved, as experienced by teachers in the Western Cape. A qualitative approach was used to conduct nine in-depth interviews with teachers. The teachers were asked to share their lived experiences about the consequences of parents being uninvolved as well as the factors that stop parents from being involved in their children’s schooling, disciplining and provision of support. The researcher aimed to investigate the experiences of teachers since they are aware of the consequences of lacking parental involvement and the influence it may have on a child with FAS. Currently, there is no research in the Western Cape that specifically centres around the teachers’ experiences of lacking parent involvement and the consequences thereof. Research has been done on the prevalence and prevention of FAS although little attention has been given to the role of a parent and their involvement and the possible negative consequences when the parents are uninvolved. The study also aimed to shed light on the unique challenges FAS learners pose in terms of discipline as well as the influences that a lack of parenting may have on a FAS child’s behaviour and consequently their future. / Olu phando lwenziwa ngenjongo yokuqwalasela iziqhamo zokuchaphazeleka butywala kubantwana abesesesibelekweni, le nto kuthiwa yifoetal alcohol syndrome (FAS) ngesiNgesi. Kwaqwalaselwa ezi ziqhamo kubantwana abasesikolweni, xa abazali babo bengathathi nxaxheba emfundweni yabo, ngokwamava eetitshala zephondo laseNtshona Koloni. Kwasetyenziswa uphando olusekelwe kwiingxoxo nokuzathuza, ngokuqhuba udliwano ndlebe olunzulu neetitshala ezilithoba. Ezi titshala zacelwa ukuba zibalise ngamava azo ngeziqhamo zokungazibandakanyi kwabazali kwakunye nezinto ezibangela ukuba bangazibandakanyi abazali ekufundeni kwabantwana babo, ekubaqeqesheni nasekubaxhaseni. Umphandi wayejolise ekuphandeni amava eetitshala kuba zona ziyazibona iziqhamo zokungazibandakanyi kwabazali nendlela le nto inokumchaphazela ngayo umntwana one-FAS. Sithetha nje, alukho uphando eNtshona Koloni olugxininisa kumava eetitshala malunga nokungazibandakanyi kwabazali neziqhamo zoko. Lukhona uphando olwenziweyo ngokuxhaphaka nokuthintela i-FAS kodwa ayikafumani ngqwalasela indima yomzali nokuzibandakanya kunye neziqhamo ezibi zokungazibandakanyi kwabazali. Olu phando lwalukwajolise ekuboniseni imingeni eveliswa ngabantwana abane-FAS xa beqeqeshwa, kunye nefuthe lokungabikho kwenkxaso yobuzali emntwaneni one-FAS kwisimilo sakhe nekamva lakhe. / Educational Studies / M. Ed. (Sosio-Opvoedkunde)

La consommation d’alcool pendant la grossesse peut entraîner des conséquences néfastes sur le développement de l’enfant et mener aux troubles du spectre de l’alcoolisation fœtale (TSAF). Cependant on en connaît peu sur son effet durant la période de préimplantation. Cette période est reconnue comme étant sensible à l’environnement, majoritairement dû au fait qu’elle est caractérisée par la reprogrammation dynamique des profils de méthylation de l’ADN. L’alcool est reconnu pour altérer les mécanismes impliqués dans les processus de méthylation de l’ADN (e.g., cycle du folate, actions des DNMTs). Récemment, nous avons démontré qu’une exposition prénatale à l’alcool éthylique durant la préimplantation altère les futurs profils de méthylation de l’ADN du cerveau et augmente le nombre de défauts morphologiques à la mi-gestation. Il n’y a présentement aucun traitement pour les TSAF, mais certaines études suggèrent qu’une diète enrichie en donneurs de groupement méthyles (e.g., folate, choline), nécessaires aux réactions de méthylation, pourrait atténuer les effets d’une exposition prénatale à l’alcool. C’est pourquoi nous avons voulu déterminer si une diète enrichie en donneurs de groupements méthyles pouvait apporter une protection aux embryons ayant subi une exposition prénatale à l’alcool durant la préimplantation. Pour ce faire, une diète standard ou enrichie a été donné à des souris 4 semaines avant la gestation et pendant celle-ci. Les femelles gestantes ont reçu une dose d’alcool au jour E2.5, puis nous avons récolté les embryons à E10.5 et E18.5 pour évaluer les anomalies physiques et faire l’analyse de la méthylation des cerveaux antérieurs. Nos résultats démontrent que la diète enrichie prévient ou élimine un certain nombre de défauts morphologiques à E10.5 et E18.5. Nous avons aussi observé que la diète enrichie n’affectait pas la mise en place et le maintien de la méthylation et l’expression des gènes à empreintes durant le développement. La diète enrichie en donneurs de groupements méthyles aide donc à prévenir certains effets nuisibles de l’exposition prénatale à l’alcool survenant durant la préimplantation. / Alcohol consumption during pregnancy can have a significant impact on the development of the child and lead to fetal alcohol spectrum disorders (FASD). Nonetheless, little is known about its effect during the pre-implantation period. However, we know that this period is very sensitive to the environment, mainly because of major reprogramming of DNA methylation patterns. Moreover, alcohol can alter the mechanisms involved in DNA methylation processes (e.g., folate cycle, actions of DNMTs). Recently, we have shown that prenatal alcohol exposure (PAE) during preimplantation alters future DNA methylation patterns of the young embryo brain and increases the number of morphological defects. There is currently no treatment for FASD, but studies suggest that a diet enriched in methyl donors (e.g., folate, choline), which are necessary for methylation reactions, may mitigate the effects of PAE. Therefore, we wanted to determine if a diet enriched in methyl group donors could provide protection to embryos against a PAE during preimplantation. To do so, a standard or enriched diet was given to mice 4 weeks before and during gestation. Pregnant females were exposed to alcohol at day E2.5, then we harvested embryos (E10.5, E18.5) to assess physical abnormalities and analyse forebrain methylation. Our results demonstrate that the enriched diet reduces or eliminate defects at E10.5 and E18.5. We also observed that the fortified diet did not affect the establishment and maintenance of methylation and expression of imprinted genes during development. Thus, our results show that a methyl enriched diet can prevent some of the adverse effects of prenatal alcohol exposure occurring during preimplantation.