Browsing by Subject "Ethanol exposure"

Now showing 1 - 3 of 3
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    Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: prevention with folic acid
    (Wiley, 2013-10) Swapnalee, Sarmah; Marrs, James A.; Biology, School of Science
    Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS: Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbs multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis, and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS: Our results indicate that ethanol exposure interrupted divergent cardiac morphogenetic events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects.
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    Embryonic Ethanol Exposure Affects Early- and Late-Added Cardiac Precursors and Produces Long-Lasting Heart Chamber Defects in Zebrafish
    (MDPI, 2017-12-01) Sarmah, Swapnalee; Marrs, James A.; Biology, School of Science
    Drinking mothers expose their fetuses to ethanol, which produces birth defects: craniofacial defects, cognitive impairment, sensorimotor disabilities and organ deformities, collectively termed as fetal alcohol spectrum disorder (FASD). Various congenital heart defects (CHDs) are present in FASD patients, but the mechanisms of alcohol-induced cardiogenesis defects are not completely understood. This study utilized zebrafish embryos and older larvae to understand FASD-associated CHDs. Ethanol-induced cardiac chamber defects initiated during embryonic cardiogenesis persisted in later zebrafish life. In addition, myocardial damage was recognizable in the ventricle of the larvae that were exposed to ethanol during embryogenesis. Our studies of the pathogenesis revealed that ethanol exposure delayed differentiation of first and second heart fields and reduced the number of early- and late-added cardiomyocytes in the heart. Ethanol exposure also reduced the number of endocardial cells. Together, this study showed that ethanol-induced heart defects were present in late-stage zebrafish larvae. Reduced numbers of cardiomyocytes partly accounts for the ethanol-induced zebrafish heart defects.
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    Ethanol pre-exposure does not increase delay discounting in P rats, but does impair the ability to dynamically adapt behavioral allocation to changing reinforcer contingencies
    (Elsevier, 2019-12) Beckwith, Steven Wesley; Czachowski, Cristine Lynn; Psychology, School of Science
    Increased subjective discounting of delayed rewards is associated with substance abuse, and individuals tend to discount their drug of choice at a greater rate compared to monetary rewards. While there is evidence indicating that increased delay discounting (DD) is a risk factor for substance abuse, some results suggest that exposure to drugs of abuse also increases DD, but effects are mixed. The current study examined whether ethanol pre-exposure increases DD and if an ethanol reinforcer would be discounted at a greater rate than sucrose. Alcohol preferring (P) rats were pre-exposed to either ethanol or sucrose using an intermittent access protocol (IAP) for 8 weeks. Then animals completed an operant fixed choice procedure where each pre-exposure group was split into either an ethanol or sucrose reinforcer group. Afterwards, animals completed an adjusting delay DD task using the same groups as the fixed choice task. Animals that received access to ethanol in the IAP showed increased delayed reward preference in a delay and session dependent manner. Specifically, ethanol pre-exposed animals took more sessions to decrease their preference for the delayed reward at longer delays. In the adjusting delay task, no differences in mean adjusting delays were seen, but ethanol pre-exposure impaired animals' ability to reach stability criteria. The observed results are not consistent with ethanol pre-exposure causing a change in DD. Rather they indicate ethanol pre-exposure impaired animals' ability to reallocate their behavior in response to a change in reinforcer contingencies. The current findings extend prior results showing alcohol naïve P rats exhibit both increased DD and decreased response inhibition (Beckwith and Czachowski 2014, 2016) by demonstrating that after alcohol exposure they exhibit a form of behavioral inflexibility. Hence, a "two-hit" genetic vulnerability/environmental acceleration of addictive behavior is supported.