Prenatal ethanol exposure in C57 mice: Effects on pregnancy and offspring development

Middaugh, Lawrence D.; Randall, Carrie L.; Favara, Jean P.

doi:10.1016/0892-0362(88)90082-7

Cited by 43 publications

(20 citation statements)

References 8 publications

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“…For the ethanol diet, 15.3 ml (4.49% v/v; 25% EDC) of 95% ethanol was added to the fortified sustacal formula with water to make 320 ml of diet with 1 cal/ml (ethanol). For the isocaloric control diet, 20.2 g Maltose Dextrin was added to the fortified sustacal formula with water to bring it to 1 cal/ml (Middaugh et al, 1988, Middaugh and Boggan, 1995). One day before treatment, the ALC, PF, PF/CLN, and ALC/CLN dams were adapted to the liquid diet.…”

Section: Methodsmentioning

confidence: 99%

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

et al. 2009

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Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weightmatched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ALC combined with administration (i.p.) of CLN (20 μg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 μg/20 g body weight). On E13, fetal brains were collected and assayed for TUNEL staining, caspase-3 colorimetric assay, ELISA, and MSD electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c. Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies.

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Section: Methodsmentioning

confidence: 99%

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

et al. 2009

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“…For instance, pups from dams receiving 20 or 25% of their calories from ethanol from G5 through G18 did not display significantly different activity from controls at P12, P20, P28, or P36 in an open field paradigm [72]. In addition, exposure to 5 g/kg ethanol on P7 in 2 doses of 2.5 g/kg given 2 h apart had no effect on locomotor activity in rats examined in an open field for 35 min at P35 [73].…”

Section: Discussionmentioning

confidence: 99%

Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure

Susick

Lowing

Bosse

et al. 2014

Behavioural Brain Research

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Neonatal alcohol exposure in rodents causes dramatic neurodegenerative effects throughout the developing nervous system, particularly in the striatum, acutely after exposure. These acute neurodegenerative effects are augmented in mice lacking adenylyl cyclases 1 and 8 (AC1/8) as neonatal mice with a genetic deletion of both AC isoforms (DKO) have increased vulnerability to ethanol-induced striatal neurotoxicity compared to wild type (WT) controls. While neonatal ethanol exposure is known to negatively impact cognitive behaviors, such as executive functioning and working memory in adolescent and adult animals, the threshold of ethanol exposure required to impinge upon developmental behaviors in mice has not been extensively examined. Therefore, the purpose of this study was to determine the behavioral effects of neonatal ethanol exposure using various striatal-dependent developmental benchmarks and to assess the impact of AC1/8 deletion on this developmental progression. WT and DKO mice were treated with 2.5 g/kg ethanol or saline on postnatal day (P)6 and later subjected to the wire suspension, negative geotaxis, postural reflex, grid hang, tail suspension and accelerating rotarod tests at various time points. At P30, mice were evaluated for their hypnotic responses to 4.0 g/kg ethanol by using the loss of righting reflex assay and ethanol-induced stimulation of locomotor activity after 2.0 g/kg ethanol. Ethanol exposure significantly impaired DKO performance in the negative geotaxis test while genetic deletion of AC1/8 alone increased grid hang time and decreased immobility time in the tail suspension test with a concomitant increase in hindlimb clasping behavior. Locomotor stimulation was significantly increased in animals that received ethanol as neonates, peaking significantly in ethanol-treated DKO mice compared to ethanol-treated WT controls, while sedation duration following high-dose ethanol challenge was unaffected. These data indicate that the maturational parameters examined in the current study may not be sensitive enough to detect effects of a single ethanol exposure during the brain growth spurt period. Genetic deletion of AC1/8 reveals a role for these cylases in attenuating ethanol-induced behavioral effects in the neonatally-exposed adolescent.

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“…On the other hand, mixed results have been reported on the effects of alcohol during the prenatal period in mice, corresponding to human organogenesis [Becker et al, 1989;Downing et al, 2009;Middaugh et al, 1988;Mothes et al, 1996]. Consensus suggests that it is the initial few days of mouse postnatal growth, corresponding to the first 2-3 weeks of the human brain growth spurt, which dictate the period when the effects of alcohol are detrimental.…”

Section: Prevention Of Fasmentioning

confidence: 94%

Screening, Diagnosing and Prevention of Fetal Alcohol Syndrome: Is This Syndrome Treatable

Ismail¹,

Buckley²,

Budacki³

et al. 2010

Dev Neurosci

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Prenatal alcohol exposure can lead to a wide range of adverse effects on a developing fetus. As a whole, these teratogenic outcomes are generally known as fetal alcohol spectrum disorders, the most severe of which is fetal alcohol syndrome (FAS). Clinically, children diagnosed with FAS vary greatly in their presentation of symptoms, likely due to the amount of alcohol and timing of exposure, as well as maternal and genetic influences. All these factors play a role in determining the mechanisms through which alcohol damages a developing brain, the details of which are still largely unknown. However, continuing research and recent developments have provided promising results that may lead to screening mechanisms and treatment therapies for children with FAS. Here we review the teratogenic effects of alcohol, strategies for detecting maternal alcohol consumption, identification of fetal biological markers, and prevention methods for FAS.

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Prenatal ethanol exposure in C57 mice: Effects on pregnancy and offspring development

Cited by 43 publications

References 8 publications

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure

Screening, Diagnosing and Prevention of Fetal Alcohol Syndrome: Is This Syndrome Treatable

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