Sandra M Mooney1, Eneda Pjetri2, Walter B Friday2, Susan M Smith3. 1. Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA; Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA. 2. Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA. 3. Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA; Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA. Electronic address: Susan_Smith@unc.edu.
Abstract
BACKGROUND: Prenatal alcohol exposure (PAE) can produce behavioral deficits in the presence or absence of growth and morphological deficits. Here, we describe a murine PAE model having parallels to the clinical diagnosis of alcohol-related neurodevelopmental deficit (ARND). METHODS: Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3 g/kg) or maltodextrin daily on embryonic days (E) E8.5 through E17.5. Blood alcohol levels were 211 ± 14 mg/dL at 30 min post-gavage. Offspring behavior was tested at adolescence. RESULTS: ALC dams gained less weight during the alcohol exposure period (p = 0.035). ALC male and female pups weighed more than controls at P15 (p ≤ 0.001) and P22 (p ≤ 0.001), but not at P37, perhaps because their dams were pair-housed. During the training session for accelerating rotarod, control offspring trended to stay longer on the rotarod than did ALC offspring [F(1,54) = 2.892, p = 0.095]. In the Y-maze, ALC offspring had a higher percent alternation than did controls [F(1,54) = 16.577, p < 0.001], but activity level did not appear to differ. In the fear-conditioning test, there was no ALC effect in the training trial. In the contextual test, there was a group × minute effect for males [F(4,120) = 2.94, p = 0.023], and ALC trended to freeze less than controls in minute 1 (p = 0.076) and froze less in minute 2 (p = 0.02). In the cue test, there was a trend for a group-sex interaction [F(1,53) = 3.008, p = 0.089] on overall freezing, such that ALC males (p < 0.05) again froze less than control males, whereas ALC females (p < 0.05) froze more than control females. CONCLUSIONS: This mouse model of PAE, using a repeated intermediate exposure, produces modest behavioral impairments that are consistent along the continuum of PAE models, including deficits in associative memory and hyper-responsivity. The lack of growth or morphological deficits suggests these mice may model aspects of ARND.
BACKGROUND: Prenatal alcohol exposure (PAE) can produce behavioral deficits in the presence or absence of growth and morphological deficits. Here, we describe a murine PAE model having parallels to the clinical diagnosis of alcohol-related neurodevelopmental deficit (ARND). METHODS: Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3 g/kg) or maltodextrin daily on embryonic days (E) E8.5 through E17.5. Blood alcohol levels were 211 ± 14 mg/dL at 30 min post-gavage. Offspring behavior was tested at adolescence. RESULTS: ALC dams gained less weight during the alcohol exposure period (p = 0.035). ALC male and female pups weighed more than controls at P15 (p ≤ 0.001) and P22 (p ≤ 0.001), but not at P37, perhaps because their dams were pair-housed. During the training session for accelerating rotarod, control offspring trended to stay longer on the rotarod than did ALC offspring [F(1,54) = 2.892, p = 0.095]. In the Y-maze, ALC offspring had a higher percent alternation than did controls [F(1,54) = 16.577, p < 0.001], but activity level did not appear to differ. In the fear-conditioning test, there was no ALC effect in the training trial. In the contextual test, there was a group × minute effect for males [F(4,120) = 2.94, p = 0.023], and ALC trended to freeze less than controls in minute 1 (p = 0.076) and froze less in minute 2 (p = 0.02). In the cue test, there was a trend for a group-sex interaction [F(1,53) = 3.008, p = 0.089] on overall freezing, such that ALC males (p < 0.05) again froze less than control males, whereas ALC females (p < 0.05) froze more than control females. CONCLUSIONS: This mouse model of PAE, using a repeated intermediate exposure, produces modest behavioral impairments that are consistent along the continuum of PAE models, including deficits in associative memory and hyper-responsivity. The lack of growth or morphological deficits suggests these mice may model aspects of ARND.
Authors: Ana Maria Cebolla; Guy Cheron; Raphael Hourez; Bertrand Bearzatto; Bernard Dan; Laurent Servais Journal: Neurosci Lett Date: 2009-03-17 Impact factor: 3.046
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Authors: Manjot S Virdee; Nipun Saini; Colin D Kay; Andrew P Neilson; Sze Ting Cecilia Kwan; Kaylee K Helfrich; Sandra M Mooney; Susan M Smith Journal: Sci Rep Date: 2021-01-08 Impact factor: 4.379
Authors: Nipun Saini; Manjot S Virdee; Kaylee K Helfrich; Sze Ting Cecilia Kwan; Sandra M Mooney; Susan M Smith Journal: Nutrients Date: 2022-03-05 Impact factor: 6.706
Authors: Susan M Smith; Eneda Pjetri; Walter B Friday; Brandon H Presswood; Dane K Ricketts; Kathleen R Walter; Sandra M Mooney Journal: Nutrients Date: 2022-03-30 Impact factor: 5.717