PMID- 28476615 OWN - NLM STAT- MEDLINE DCOM- 20180430 LR - 20180430 IS - 1872-9738 (Electronic) IS - 0892-0362 (Linking) VI - 62 DP - 2017 Jul TI - Deficits in spatial learning and memory in adult mice following acute, low or moderate levels of prenatal ethanol exposure during gastrulation or neurulation. PG - 42-54 LID - S0892-0362(16)30167-2 [pii] LID - 10.1016/j.ntt.2017.05.001 [doi] AB - Debate continues on the merits of strictly limiting alcohol consumption during all of pregnancy, and whether "safe" consumption levels and/or times exist. Only a relatively few experimental studies have been conducted that limit the timing of exposure to specific events during development and the exposure level to one that might model sporadic, incidental drinking during pregnancy. In the present study, the effects of two acute gavage exposures to low and moderate levels of ethanol (peak blood ethanol concentrations (BEC) of 104 and 177mg/dl, respectively) either during gastrulation on gestational day (GD) 7 (at GD7:0h and GD7:4h) or during neurulation on GD8 (at GD8:6h and GD8:10h) on the spatial learning and memory abilities of adult mice in the radial arm maze (RAM) were examined. Mice were selected from a prenatal ethanol exposure (PAE) cohort that had been tested as neonates for their sensorimotor development (Schambra et al., 2015) and as juveniles and young adults for open field activity levels and emotionality (Schambra et al., 2016). Mice exposed on either of the two gestational days to acute, low or moderate levels of ethanol were deficient in overall performance in the RAM in adulthood. Importantly, mice in ethanol exposed groups took longer to reach criterion in the RAM, and many mice in these groups failed to do so after 48 trials when testing was terminated. Exposure to a low level of ethanol on either GD7 or GD8, or a moderate level on GD7, resulted in significant impairment in spatial reference (long-term) memory, while only mice exposed on GD7 to the low level of ethanol were significantly impaired in spatial working (short-term) memory. Mice exposed to the low ethanol level on either day had significantly shorter response latencies, which may reflect impairment of processes related to response inhibition or executive attention in these mice. For all measures, distributions of individual scores revealed a relatively small subset of mice in each PAE group who scored well outside the range of the control group, which skewed the population distributions to varying degrees in the direction of worse performance for the PAE groups. Overall the data suggest that after acute, low level ethanol exposure early in gestation, the likelihood that an individual mouse embryo experienced measureable ill-effects due to the exposure was rather low, but in a few of the embryos, damage occurred that resulted in significant deficits in later performance. The overall characteristics of our cohort of PAE mice, including delayed sensorimotor development, mild hypoactivity and increased emotionality, as shown in previous studies, together with deficits in spatial learning and memory as shown here, resemble those in a subset of human Fetal Alcohol Spectrum Disorder (FASD) diagnoses, specifically ADHD-Inattentive type (ADHD-I) and/or Sluggish Cognitive Tempo (SCT). Although possible correspondences between mechanisms underlying PAE-induced deficits in mice and those operating in humans remain undefined, further study with this mouse PAE model may ultimately help advance understanding of the causes of these conditions in affected children. This study highlights the possibility of risk associated with low to moderate sporadic alcohol consumption during the first month of human pregnancy. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Schambra, Uta B AU - Schambra UB AD - Department Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. Electronic address: schambra@etsu.edu. FAU - Lewis, C Nicole AU - Lewis CN AD - Department of Mathematics & Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, TN 37614, USA. FAU - Harrison, Theresa A AU - Harrison TA AD - Department Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. LA - eng PT - Journal Article DEP - 20170502 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 3K9958V90M (Ethanol) SB - IM MH - Animals MH - Ethanol/*toxicity MH - Female MH - *Gastrulation MH - Male MH - Memory Disorders/chemically induced MH - Memory, Short-Term/drug effects MH - Mice, Inbred C57BL MH - *Neurulation MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*psychology MH - Spatial Learning/*drug effects MH - Spatial Memory/*drug effects OTO - NOTNLM OT - Gastrulation/neurulation OT - Low-moderate BEC OT - Memory deficits OT - Mouse OT - Radial arm maze OT - Response latency EDAT- 2017/05/10 06:00 MHDA- 2018/05/01 06:00 CRDT- 2017/05/07 06:00 PHST- 2016/12/17 00:00 [received] PHST- 2017/03/26 00:00 [revised] PHST- 2017/05/01 00:00 [accepted] PHST- 2017/05/10 06:00 [pubmed] PHST- 2018/05/01 06:00 [medline] PHST- 2017/05/07 06:00 [entrez] AID - S0892-0362(16)30167-2 [pii] AID - 10.1016/j.ntt.2017.05.001 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2017 Jul;62:42-54. doi: 10.1016/j.ntt.2017.05.001. Epub 2017 May 2.