Indiana University-Purdue University Indianapolis (IUPUI) / The GABRA2 gene, which encodes the α2 subunit of GABAA receptors, is one of the genes most frequently associated with alcohol-related behavior in human studies (Demers, Bogdan, & Agrawal, 2014). Polymorphisms in GABRA2 have been found to be associated with alcohol dependence, changes in drinking frequency, and alcohol’s stimulating and euphoric effects (Arias et al., 2014; Dick et al., 2014; Edenberg et al., 2004). However, the GABRA2-alcohol relationship may not be direct, as anxiety and impulsiveness have been found to be mediating factors (Enoch, Schwartz, Albaugh, Virkkunen, & Goldman, 2006; Villafuerte, Strumba, Stoltenberg, Zucker, & Burmeister, 2013). Comorbidity of anxiety and alcohol use disorders is both prevalent and clinically relevant (J. P. Smith & Randall, 2012), and GABAA receptors play a significant role in each. Benzodiazepines, primary pharmacologic treatments for anxiety disorders and alcohol withdrawal, facilitate signaling at GABAA receptors, and their anxiolytic effects appear to depend on the presence of α2 subunits in these receptors (Low et al., 2000). The amygdala is widely implicated in both anxiety disorders as well as addiction (Janak & Tye, 2015), and its central nucleus is an important mediator of responses to both alcohol- and stress-related stimuli (Roberto, Gilpin, & Siggins, 2012), some of which may be related to GABRA2 expression within this region (Jin et al., 2014). The aim of the current study was to explore the role of Gabra2 (mouse ortholog of GABRA2) expression within the central nucleus of the amygdala (CeA) in anxiety-related behavior and alcohol’s anxiolytic effects in mice. C57BL/6J (B6) mice underwent surgery for bilateral infusion of GFP-tagged lentivirus targeting Gabra2 or a scramble control lentivirus into the CeA. Following 12-13 days of recovery, mice were assessed for anxiety-like behavior in the elevated plus maze (EPM) naïve or following IP injection of 0, 0.75, or 1.5 g/kg ethanol. After assessment, brains were extracted and sectioned through the CeA. Finally, GFP was quantified, the CeA was collected via laser microdissection, and α2 protein was quantified via ELISA. In mice expressing GFP in the CeA, α2 protein concentrations were lower for Virus mice relative to Control mice. The EPM was anxiogenic, and alcohol was found to be anxiolytic. In naïve mice, while there was no difference between Control mice and Virus mice on any behavioral measure, there were significant correlations between CeA α2 protein concentration and time spent in closed arms as well as both total and average time spent in open arms. In mice receiving injection of 0, 0.75, or 1.5 g/kg ethanol, there was a main effect of dose on several behavioral measures, but no interaction between viral condition and dose, and only a main effect of viral condition on average time spent in closed arms. There were no significant correlations between CeA α2 protein concentration and behavioral measures within any injected dose. These results are consistent with GABRA2-anxiety associations and effects of Gabra2 manipulation on anxiety-like behavior. Furthermore, they suggest that CeA α2 protein concentration is positively related to basal anxiety, which could affect alcohol use through various routes. However, these results also suggest that CeA α2 protein concentration is not related to alcohol’s anxiolytic capacity, at least when acutely administered in alcohol-naïve animals.

A jabuticaba-sabará (Plinia jaboticaba (Vell.) Berg) é uma fruta nativa da Mata Atlântica que possui alto teor de antocianinas, proantocianidinas e elagitaninos, fenólicos associados com diversos benefícios à saúde. O objetivo deste trabalho foi avaliar o efeito de dois extratos ricos em compostos fenólicos da jabuticaba-sabará sobre a massa corporal e o metabolismo da glicose e dos lipídios de camundongos alimentados com dieta rica em lipídios e sacarose (HLS). Foram utilizados 40 camundongos machos C57BL/6J com oito semanas de idade e alimentados com ração padrão para camundongos ou dieta HLS durante oito semanas. Os animais foram divididos aleatoriamente em quatro grupos de dez. Os dois primeiros grupos receberam, respectivamente, ração padrão para camundongos ou dieta HLS e água ad libitum, sendo denominados, nesta ordem, grupo controle (Ct) e grupo HF. Os dois últimos grupos foram alimentados com dieta HLS recebendo, por gavagem, os extratos ricos em compostos fenólicos, sendo denominados grupo C18 e PA, respectivamente. Para o grupo C18 foi administrado o extrato obtido por extração em fase sólida (EFS) em colunas de octadecilsilano (C18), possuindo maior concentração de taninos. O grupo PA recebeu o extrato obtido por EFS em colunas de poliamida (PA), resultando em um extrato com menor concentração de taninos em relação ao extrato C18. A dose de fenólicos administrada aos animais foi de 50 mg equivalentes de ácido gálico (EAG)/kg de massa corporal para ambos os grupos. Na sexta semana foi realizado o teste de tolerância à insulina (ITT) e, na sétima, o teste oral de tolerância à glicose (OGTT). Além da massa corporal, os animais foram também avaliados quanto a glicemia, insulinemia e perfil lipídico (colesterol total, HDL, LDL e triacilgliceróis). Os grupos suplementados apresentaram menor ganho de massa dos tecidos adiposos brancos em comparação ao grupo HF (43% para o grupo C18 e 28% para o grupo PA). Além disto, ambos os extratos atenuaram os níveis de glicose e o extrato C18 melhorou os níveis de insulina plasmática, colesterol total e triacilgliceróis hepáticos. Portanto, extratos ricos em compostos fenólicos da jabuticaba-sabará foram eficientes na prevenção do ganho de massa corporal, evitando o crescimento excessivo dos tecidos adiposos brancos, de altos níveis de glicose, insulina, colesterol total e triacilgliceróis hepáticos em camundongos alimentados com dieta rica em lipídios e sacarose. / Sabará jaboticaba is a Brazilian Atlantic Forest fruit rich in anthocyanins, proanthocyanidins and ellagitannins, phenolic compounds that have been associated to several benefits to health. This work aimed to evaluate the effect of the administration of two phenolic-rich extracts from Sabará jaboticaba on body weight gain and on glucose and lipid metabolism of high-fat-sucrose-fed mice. Forty 8-week old male C57BL/6J mice were fed a low-fat chow diet or a high fat, high-sucrose (HFHS) diet for 8 weeks. The animals were randomly divided into four groups of ten mice each. The first two groups received, respectively, a low-fat chow diet or a HFHS diet and water ad libitum and were nominated, in order, control (Ct) and HF group. The last two groups were fed a HFHS diet and received by gavage the phenolic-rich extracts, being respectively nominated C18 and PA group. The C18 group received an extract obtained by solid phase extraction (SPE) in octadecylsilane (C18) column, therefore the most concentrated in tannins. The PA group received an extract obtained by SPE in polyamide (PA) column, therefore less concentrated in tannins. The dose of phenolics administered to animals was of 50 mg acid gallic equivalent (GAE)/kg body weight, for both groups. The insulin tolerance test (ITT) was performed in the sixth week and the oral glucose tolerance test (OGTT) in the seventh week. In addition, the animals were assessed for glycaemia, insulinemia and lipid profile (total-, HDL-, LDL-cholesterol and triacylglycerols). The supplemented groups had lower white adipose tissue gain than HF group (43% for the C18 group and 28% for the PA group). In addition, both extracts attenuated hyperglycemia and the C18 extract improved the plasmatic insulin levels, total cholesterol and hepatic triacylglycerol content. Thus, phenolic-rich extracts from Sabará jaboticaba were effective in preventing body weight gain, avoiding the overgrowth of white adipose tissues, and high levels of glucose, insulin, total cholesterol and hepatic triacylglycerols in HFHS-fed C57BL/6J mice.

A jabuticaba-sabará (Plinia jaboticaba (Vell.) Berg) é uma fruta nativa da Mata Atlântica que possui alto teor de antocianinas, proantocianidinas e elagitaninos, fenólicos associados com diversos benefícios à saúde. O objetivo deste trabalho foi avaliar o efeito de dois extratos ricos em compostos fenólicos da jabuticaba-sabará sobre a massa corporal e o metabolismo da glicose e dos lipídios de camundongos alimentados com dieta rica em lipídios e sacarose (HLS). Foram utilizados 40 camundongos machos C57BL/6J com oito semanas de idade e alimentados com ração padrão para camundongos ou dieta HLS durante oito semanas. Os animais foram divididos aleatoriamente em quatro grupos de dez. Os dois primeiros grupos receberam, respectivamente, ração padrão para camundongos ou dieta HLS e água ad libitum, sendo denominados, nesta ordem, grupo controle (Ct) e grupo HF. Os dois últimos grupos foram alimentados com dieta HLS recebendo, por gavagem, os extratos ricos em compostos fenólicos, sendo denominados grupo C18 e PA, respectivamente. Para o grupo C18 foi administrado o extrato obtido por extração em fase sólida (EFS) em colunas de octadecilsilano (C18), possuindo maior concentração de taninos. O grupo PA recebeu o extrato obtido por EFS em colunas de poliamida (PA), resultando em um extrato com menor concentração de taninos em relação ao extrato C18. A dose de fenólicos administrada aos animais foi de 50 mg equivalentes de ácido gálico (EAG)/kg de massa corporal para ambos os grupos. Na sexta semana foi realizado o teste de tolerância à insulina (ITT) e, na sétima, o teste oral de tolerância à glicose (OGTT). Além da massa corporal, os animais foram também avaliados quanto a glicemia, insulinemia e perfil lipídico (colesterol total, HDL, LDL e triacilgliceróis). Os grupos suplementados apresentaram menor ganho de massa dos tecidos adiposos brancos em comparação ao grupo HF (43% para o grupo C18 e 28% para o grupo PA). Além disto, ambos os extratos atenuaram os níveis de glicose e o extrato C18 melhorou os níveis de insulina plasmática, colesterol total e triacilgliceróis hepáticos. Portanto, extratos ricos em compostos fenólicos da jabuticaba-sabará foram eficientes na prevenção do ganho de massa corporal, evitando o crescimento excessivo dos tecidos adiposos brancos, de altos níveis de glicose, insulina, colesterol total e triacilgliceróis hepáticos em camundongos alimentados com dieta rica em lipídios e sacarose. / Sabará jaboticaba is a Brazilian Atlantic Forest fruit rich in anthocyanins, proanthocyanidins and ellagitannins, phenolic compounds that have been associated to several benefits to health. This work aimed to evaluate the effect of the administration of two phenolic-rich extracts from Sabará jaboticaba on body weight gain and on glucose and lipid metabolism of high-fat-sucrose-fed mice. Forty 8-week old male C57BL/6J mice were fed a low-fat chow diet or a high fat, high-sucrose (HFHS) diet for 8 weeks. The animals were randomly divided into four groups of ten mice each. The first two groups received, respectively, a low-fat chow diet or a HFHS diet and water ad libitum and were nominated, in order, control (Ct) and HF group. The last two groups were fed a HFHS diet and received by gavage the phenolic-rich extracts, being respectively nominated C18 and PA group. The C18 group received an extract obtained by solid phase extraction (SPE) in octadecylsilane (C18) column, therefore the most concentrated in tannins. The PA group received an extract obtained by SPE in polyamide (PA) column, therefore less concentrated in tannins. The dose of phenolics administered to animals was of 50 mg acid gallic equivalent (GAE)/kg body weight, for both groups. The insulin tolerance test (ITT) was performed in the sixth week and the oral glucose tolerance test (OGTT) in the seventh week. In addition, the animals were assessed for glycaemia, insulinemia and lipid profile (total-, HDL-, LDL-cholesterol and triacylglycerols). The supplemented groups had lower white adipose tissue gain than HF group (43% for the C18 group and 28% for the PA group). In addition, both extracts attenuated hyperglycemia and the C18 extract improved the plasmatic insulin levels, total cholesterol and hepatic triacylglycerol content. Thus, phenolic-rich extracts from Sabará jaboticaba were effective in preventing body weight gain, avoiding the overgrowth of white adipose tissues, and high levels of glucose, insulin, total cholesterol and hepatic triacylglycerols in HFHS-fed C57BL/6J mice.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Sabe-se que o flúor causa alterações químicas e celulares no osso, dependendo da dosagem e do tempo de exposição a esse elemento. Já foi demonstrado que alterações clínicas importantes, como a osteoporose, osteopetrose e esclerose óssea, podem ser geradas pela ingestão de flúor. Sabe-se que o flúor pode guiar os osteoblastos ao crescimento, sob doses e tempos de exposição específicos. A sensibilidade dos tecidos mineralizados ao fluoreto responde a mecanismos genéticos inerentes a cada população. Dentro de uma mesma espécie, diferentes linhagens apresentam um comportamento distinto frente a esse fármaco. Durante várias décadas, os estudos com fluoretos resumiram-se ao fluoreto de sódio, amplamente utilizado na prevenção das cáries dentárias. Recentemente, outras fontes de fluoretos como TiF4 e SnF2 têm sido buscadas, com intuito de potencializar as vantagens desse elemento. Porém não existem estudos ainda sobre o efeito do AlF3 sobre o tecido ósseo até a presente data. Desse modo, achamos oportuno investigar seu papel, quando administrado a células ósseas e para tal, investigamos a viabilidade e padrão de atividade das fosfatases desse sal (AlF3) quando administrado às células da linhagem pré-osteblástica MC3T3, em comparação ao NaF. Além disso, sabendo que diferentes células apresentam comportamento distinto ao tratamento com fluoretos, estudamos o papel do NaF quando administrado a duas linhagens celulares de camundongos com densidades ósseas distintas e com diferentes susceptibilidades ao fluoreto: C3H/HeJ e C57BL/6J (C3H e C57, alta e baixa densidades ósseas, respectivamente). As células também foram avaliadas quanto à viabilidade celular e ao perfil das fosfatases. Todos os resultados foram submetidos à Análise de Variância a três critérios e nos permitiu identificar que entre os sais de fluoreto, apenas o NaF promoveu alterações na viabilidade celular das células MC3T3. O AlF3 não exerceu influência na atividade da fosfatase alcalina quando consideramos as células pré-osteoblásticas, no entanto, o efeito desse fluoreto sobre a atividade das fosfatases ácidas totais e ácida resistente ao tartarato ocorre de modo dicotômico. Quando consideramos uma população celular heterogênea, coletada de calvária, como foi o caso das linhagens C3H e C57, verificamos que o NaF interferiu tanto sobre a proliferação, quanto a atividade das fosfatases de modo bastante distinto para ambas linhagens celulares. Assim concluimos que o NaF é capaz de exercer efeitos mais diversificados em diferentes tipos celulares, alterando viabilidade celular e atividade de enzimas; em contrapartida, o AlF3 produz efeitos mais especifícos e delimitados em pré-osteoblastos. / It is well known that fluoride causes chemical and cellular alteration on bone tissue, depending on the dosage and time of exposure to this element. Several studies have been conducted to show that some bone diseases, such as osteoporosis, osteopetrosis and esclerosis, can occur as a consequence of the excessive fluoride uptake. Fluoride can lead osteoblast to proliferate, under certain conditions as time and dosage. The same way, excessive dosages of fluoride can alter protein activity in osteoblasts, by changing the expression of retated genes. Sensitivity of mineralized tissues to fluoride depends on a genetic background inherent to each population. Within the same specie, different lineages present distint behavior to the ingestion of this íon. Over several decades, many researches focused on the study of NaF as the only source of fluoride, once it is wide spread used to the prevention of dental caries. More recently, different sources of fluoride have been assessed, like TiF4 e SnF2</sub, with the main aim to enhance biochemical and physical benefits of this element. Despite of this, none of these formulations have been tested to evaluate their effect on the bone tissue. Thus, we believe it is advisable to investigate viability and phosphatases activities of pre-osteoblast MC3T3 cells treated with Aluminium fluoride, compared to NaF treatments. Besides this, facing the knowledge that different cell lines have distinct behavior when treated with fluoride, we used two inbred strains of mice with distint mineral bone densities, C3H/HeJ (C3H, high bone density) and C57BL/6J (C57, low bone density), to assess the viability and phosphatases activities after the treatment with NaF. Overall results were tested by 3 way- Anova. AlF3 did not exibit influence over on alkaline phosphatase when pre-osteoblast cells are considered, but the effect of this fluoride salt on the activity of total and tartarate resistant acid phosphatases ocurrs on a dicotomic way. When we consider a mixed cell population, collected from calvária as for the C3H and C57 assays, NaF did interfered as with the proliferation rate as phosphatase activities on a very distinct fashion between the two lineages. Thus, it is possible to conclude that NaF is able to exert variable effects in different cell types and enzyme activities; on the other hand, AlF3 effects are more specific and surrounded in pre-osteblastic cells.

Sabe-se que o flúor causa alterações químicas e celulares no osso, dependendo da dosagem e do tempo de exposição a esse elemento. Já foi demonstrado que alterações clínicas importantes, como a osteoporose, osteopetrose e esclerose óssea, podem ser geradas pela ingestão de flúor. Sabe-se que o flúor pode guiar os osteoblastos ao crescimento, sob doses e tempos de exposição específicos. A sensibilidade dos tecidos mineralizados ao fluoreto responde a mecanismos genéticos inerentes a cada população. Dentro de uma mesma espécie, diferentes linhagens apresentam um comportamento distinto frente a esse fármaco. Durante várias décadas, os estudos com fluoretos resumiram-se ao fluoreto de sódio, amplamente utilizado na prevenção das cáries dentárias. Recentemente, outras fontes de fluoretos como TiF4 e SnF2 têm sido buscadas, com intuito de potencializar as vantagens desse elemento. Porém não existem estudos ainda sobre o efeito do AlF3 sobre o tecido ósseo até a presente data. Desse modo, achamos oportuno investigar seu papel, quando administrado a células ósseas e para tal, investigamos a viabilidade e padrão de atividade das fosfatases desse sal (AlF3) quando administrado às células da linhagem pré-osteblástica MC3T3, em comparação ao NaF. Além disso, sabendo que diferentes células apresentam comportamento distinto ao tratamento com fluoretos, estudamos o papel do NaF quando administrado a duas linhagens celulares de camundongos com densidades ósseas distintas e com diferentes susceptibilidades ao fluoreto: C3H/HeJ e C57BL/6J (C3H e C57, alta e baixa densidades ósseas, respectivamente). As células também foram avaliadas quanto à viabilidade celular e ao perfil das fosfatases. Todos os resultados foram submetidos à Análise de Variância a três critérios e nos permitiu identificar que entre os sais de fluoreto, apenas o NaF promoveu alterações na viabilidade celular das células MC3T3. O AlF3 não exerceu influência na atividade da fosfatase alcalina quando consideramos as células pré-osteoblásticas, no entanto, o efeito desse fluoreto sobre a atividade das fosfatases ácidas totais e ácida resistente ao tartarato ocorre de modo dicotômico. Quando consideramos uma população celular heterogênea, coletada de calvária, como foi o caso das linhagens C3H e C57, verificamos que o NaF interferiu tanto sobre a proliferação, quanto a atividade das fosfatases de modo bastante distinto para ambas linhagens celulares. Assim concluimos que o NaF é capaz de exercer efeitos mais diversificados em diferentes tipos celulares, alterando viabilidade celular e atividade de enzimas; em contrapartida, o AlF3 produz efeitos mais especifícos e delimitados em pré-osteoblastos. / It is well known that fluoride causes chemical and cellular alteration on bone tissue, depending on the dosage and time of exposure to this element. Several studies have been conducted to show that some bone diseases, such as osteoporosis, osteopetrosis and esclerosis, can occur as a consequence of the excessive fluoride uptake. Fluoride can lead osteoblast to proliferate, under certain conditions as time and dosage. The same way, excessive dosages of fluoride can alter protein activity in osteoblasts, by changing the expression of retated genes. Sensitivity of mineralized tissues to fluoride depends on a genetic background inherent to each population. Within the same specie, different lineages present distint behavior to the ingestion of this íon. Over several decades, many researches focused on the study of NaF as the only source of fluoride, once it is wide spread used to the prevention of dental caries. More recently, different sources of fluoride have been assessed, like TiF4 e SnF2</sub, with the main aim to enhance biochemical and physical benefits of this element. Despite of this, none of these formulations have been tested to evaluate their effect on the bone tissue. Thus, we believe it is advisable to investigate viability and phosphatases activities of pre-osteoblast MC3T3 cells treated with Aluminium fluoride, compared to NaF treatments. Besides this, facing the knowledge that different cell lines have distinct behavior when treated with fluoride, we used two inbred strains of mice with distint mineral bone densities, C3H/HeJ (C3H, high bone density) and C57BL/6J (C57, low bone density), to assess the viability and phosphatases activities after the treatment with NaF. Overall results were tested by 3 way- Anova. AlF3 did not exibit influence over on alkaline phosphatase when pre-osteoblast cells are considered, but the effect of this fluoride salt on the activity of total and tartarate resistant acid phosphatases ocurrs on a dicotomic way. When we consider a mixed cell population, collected from calvária as for the C3H and C57 assays, NaF did interfered as with the proliferation rate as phosphatase activities on a very distinct fashion between the two lineages. Thus, it is possible to conclude that NaF is able to exert variable effects in different cell types and enzyme activities; on the other hand, AlF3 effects are more specific and surrounded in pre-osteblastic cells.

<p>Pathologies of sexual development are common in humans and reflect the precarious processes of sex determination and sexual differentiation. The gonad forms as a bipotential organ, and recent results from the Capel lab revealed that it is initially balanced between testis and ovarian fates by opposing and antagonistic signaling networks. In XY embryos, this balance is disrupted by the transient expression of the Y-linked gene, Sry, which activates genes that promote the testis pathway and oppose the ovarian pathway. While the roles of a few genes have been defined by mutation, current evidence suggests that the interactions of many genes and signaling pathways are involved in the establishment of sexual fate. For example, most cases of disorders of sexual development (DSDs) are unexplained by mutations in known sex determination genes. In addition, recent microarray studies in the mouse revealed that nearly half the transcriptome is expressed in the gonad at the time of sex determination (Embryonic day 11.5, or E11.5), and as many as 1,500 genes are expressed in a sexually dimorphic pattern at this early stage. Thus the sexual fate decision in the developing gonad likely depends on a complex network of interacting factors that converge on a critical threshold. </p><p>To begin to elucidate the transcription network topology underlying sex determination, we exploited two inbred mouse strains with well-characterized differences in sex reversal. The common inbred strain C57BL/6J (B6) is uniquely sensitive to XY male-to-female sex reversal in response to a number of genetic perturbations, while other strains, including 129S1/SvImJ (129S1) and DBA/2J (D2) are resistant to sex reversal. We hypothesized that these strain differences in gonad phenotype likely result from underlying expression differences in the gonad at the critical timepoint of E11.5. Using microarrays, we identified significant, reproducible differences in the transcriptome of the E11.5 XY gonad between B6 and 129S1 indicating that the reported sensitivity of B6 to sex reversal is consistent with a higher expression of a female-like transcriptome in B6 XY gonads. Surprisingly, a well-characterized master regulator of the testis pathway, Sox9, was found to be upregulated in the sensitive B6 background, which may serve as a compensatory mechanism to counteract the female-leaning transcriptome and activate the testis pathway in wild type B6 XY gonads.</p><p>We extended our expression analysis to a large set of F2 XY gonads from B6 and 129S1 intercrosses. From each pair of gonads, we analyzed the expression of 56 sex-associated genes by nanoliter-scale quantitative RT-PCR (qRT-PCR). The expression levels of most genes were highly variable across the F2 population, yet strong correlations among genes emerged. We employed a First-Order Conditional Independence (FOCI) algorithm to estimate the F2 coexpression network. From this unbiased analysis of XY expression data, we uncovered two subnetworks consisting of primarily male and female genes. Furthermore, we predicted roles for genes of unknown function based on their connectivity and position within the network. </p><p>To identify the genes responsible for these strain expression differences, we genotyped each F2 embryo at 128 single nucleotide polymorphisms (SNPs) located evenly throughout the 19 autosomes and X chromosome. We then employed linkage analysis to detect autosomal regions that control the expression of one or more of the 56 genes in the F2 population. These regions are termed expression quantitative trait loci, or eQTLs. We identified eQTLs for many sex-related genes, including Sry and Sox9, the key regulators of male sex determination. In addition, we identified multiple prominent trans-band eQTLs that controlled the expression of many genes. My work represents the first eQTL analysis of a developing vertebrate organ, the mouse gonad. This systems-level approach revealed the complex transcription architecture underlying sex determination, and provides a mechanistic explanation for sensitivity to sex reversal seen in some individuals.</p> / Dissertation

Fetal Alcohol Syndrome (FAS) labels children with physical, mental and behavioral deficits exposed to alcohol in utero. Current research indicates that timing of alcohol exposure of the embryo/fetus is a critical determinant of the behavioral deficits associated with FAS. This study represents a model for binge drinking, in which C57BL mouse embryos were exposed to alcohol during 2 separate critical periods of brain development, gestational day (GD) 7 or 8. As adults, the offspring were tested to determine if loco-motor activity and emotional reaction to a novel environment had been affected. Significant differences due to treatment and sex were noted for both the number of urinations (p=.005 and .001, respectively) and fecal boli (p=.011 and .001, respectively). These results suggest that the quantity of alcohol exposure in utero on the developing brain as in this binge-drinking model is critical in terms of adverse effects on behavioral outcome for the offspring.

No description available.

No description available.