About

Sandra Mooney, PhD, is an Associate Professor in the Department of Nutrition at UNC Gillings School of Global Public Health. She is affiliated with the UNC Nutrition Research Institute located in Kannapolis, NC. Dr. Mooney's research focuses on using animal models to test nutritional interventions that may ameliorate alcohol-induced deficits, particularly in the context of fetal alcohol spectrum disorders. Her work examines factors such as genes and nutrition that confer vulnerability or resistance to alcohol-related developmental issues. She holds a PhD in Anatomy and Structural Biology from the University of Otago, New Zealand, obtained in 1997.

Research topics

• Biology
• Medicine
• Biochemistry
• Computer Science
• Endocrinology
• Physiology
• Bioinformatics
• Internal medicine
• Genetics
• Psychology
• Developmental psychology
• Cognitive psychology
• Neuroscience

Selected publications

• Prenatal Choline Attenuates the Elevated Adiposity and Glucose Intolerance Caused by Prenatal Alcohol Exposure

  Cells · 2025-09-12 · 2 citations

  articleOpen accessSenior authorCorresponding

  Prenatal alcohol exposure (PAE) causes neurobehavioral deficits and metabolic syndrome in later life. Prenatal choline supplementation (PCS) improves those behavioral deficits. Here we test whether PCS also ameliorates the attendant metabolic syndrome, using an established mouse model that mirrors aspects of alcohol-related neurodevelopmental disorders. Pregnant dams were exposed to alcohol (3 g/kg) from gestational days 8.5-17.5; some dams received additional choline (175% of requirement) by a daily injection. Offspring were followed through to the age of 86 wks with respect to their body composition and glucose tolerance. We found that PAE affected these outcomes in a sex-dependent manner. Male PAE offspring exhibited an increased fat mass, liver enlargement, elevated fasting glucose, and glucose intolerance. Female PAE offspring exhibited an increased fat mass, but the glucose tolerance and fasting values were unaffected. Regardless of sex, PCS attenuated all these metabolic measures. PCS was shown previously to elevate methyl-related choline metabolites and improve fetal growth, suggesting that it acts by attenuating the in utero stressors that otherwise program the fetus for metabolic syndrome in later life. Importantly, PCS also improved the adiposity, fasting glucose, and glucose tolerance in control offspring consuming the fixed-nutrient AIN-93G diet, suggesting that its choline content (1 g/kg) may be inadequate for optimal rodent health.

  PublisherOA PDFDOI

• Alcohol Reprograms Placental Glucose and Lipid Metabolism, Which Correlate with Reduced Fetal Brain but not Body Weight in a Mouse Model of Prenatal Alcohol Exposure

  Journal of Nutrition · 2025-02-14 · 7 citations

  articleOpen access
  PublisherOA PDFDOI

• Prenatal Choline Attenuates the Elevated Adiposity and Glucose Intolerance Caused by Prenatal Alcohol Exposure

  UNC Libraries · 2025-10-08

  articleOpen accessSenior author

  Prenatal alcohol exposure (PAE) causes neurobehavioral deficits and metabolic syndrome in later life. Prenatal choline supplementation (PCS) improves those behavioral deficits. Here we test whether PCS also ameliorates the attendant metabolic syndrome, using an established mouse model that mirrors aspects of alcohol-related neurodevelopmental disorders. Pregnant dams were exposed to alcohol (3 g/kg) from gestational days 8.5–17.5; some dams received additional choline (175% of requirement) by a daily injection. Offspring were followed through to the age of 86 wks with respect to their body composition and glucose tolerance. We found that PAE affected these outcomes in a sex-dependent manner. Male PAE offspring exhibited an increased fat mass, liver enlargement, elevated fasting glucose, and glucose intolerance. Female PAE offspring exhibited an increased fat mass, but the glucose tolerance and fasting values were unaffected. Regardless of sex, PCS attenuated all these metabolic measures. PCS was shown previously to elevate methyl-related choline metabolites and improve fetal growth, suggesting that it acts by attenuating the in utero stressors that otherwise program the fetus for metabolic syndrome in later life. Importantly, PCS also improved the adiposity, fasting glucose, and glucose tolerance in control offspring consuming the fixed-nutrient AIN-93G diet, suggesting that its choline content (1 g/kg) may be inadequate for optimal rodent health.

  PublisherDOI

• Fetal Liver Weight Is Negatively Associated With Maternal Plasma Lipid Metabolites in a Mouse Model of Prenatal Alcohol Exposure and Choline Supplementation

  Current Developments in Nutrition · 2025-05-01

  articleOpen accessSenior author

  DNA was extracted from stool (50-75 mg) using Qiagen QIAmp Fast Stool DNA Mini Kits and libraries were paired-end sequenced (2x250bp) using an Illumina MiSeq.Raw sequencing files were processed into amplicon sequence variant (ASV) counts using QIIME2.Results: A total of 87 and 126 women in the SOC and PA groups, respectively, had stool samples available for 16S rRNA analysis.Women in the PA group increased their GW12 submaximal VO2 (workload corresponding to 15 on Borg's scale) 9.9% by GW24, compared to a 5.5% decrease in the SOC group between GW12 and GW24 (P < 0.01).Alpha diversity estimates, total ASVs, Shannon, and Simpson indices, showed no statistical differences between PA and SOC groups across all gestational periods.Similarly, no effect of PA was observed across any gestational period for the beta-diversity estimate, Bray-Curtis Dissimilarities.Using DESeq2 and ALDEx2 workflows, only 2 ASVs were statistically different after FDR correction at GW36: An ASV classified to the Prevotella genus was lower in the PA group while an ASV classified to the Akkermansia genus was greater in the PA group relative to SOC.Conclusions: A structured and supervised submaximal physical activity intervention improved the aerobic capacity in pregnant women with obesity, but had minimal effect on the composition of the fecal microbiota.

  PublisherOA PDFDOI

• Alcohol Exposure May Increase Prenatal Choline Needs Through Redirection of Choline into Lipid Synthesis Rather than Methyl Donation

  Metabolites · 2025-04-24 · 4 citations

  articleOpen accessSenior authorCorresponding

  Background: Prenatal alcohol exposure (PAE) can reduce fetal growth and cause neurodevelopmental disability. Prenatal choline supplements attenuate PAE-induced behavioral and growth deficits; however, the underlying mechanisms are unknown. Alcohol alters nutrient metabolism and potentially increases nutrient needs. Here, we investigate how alcohol affects choline metabolism in the maternal–fetal dyad and the role of supplemental choline. Methods: Pregnant C57BL/6J mice were assigned to one of four groups: alcohol-exposed (3 g/kg alcohol/day) or control +/− 100 mg/kg choline daily from embryonic day (E)8.5–17.5. We performed an exploratory hypothesis-generating analysis of targeted metabolomics on choline-related metabolites in the maternal liver, plasma, placenta, and fetal brain at E17.5 and Spearman correlation analyses to determine their association with gestational and fetal growth outcomes. Results: Although choline levels were largely unaffected by alcohol or choline, alcohol increased many lipid products in the CDP–choline pathway; this was not normalized by choline. Alcohol increased placental CDP–ethanolamine and reduced the maternal hepatic SAM/SAH ratio as well as dimethylglycine and the serine/glycine ratio across the dyad, suggesting a functional insufficiency in methyl donor pools. These outcomes were rescued by supplemental choline. Correlation analyses among choline metabolites and fetal growth outcomes suggest that maternal plasma methionine, serine, and the serine/glycine ratio may be predictive of maternal–fetal choline status. Conclusions: The increased hepatic lipid synthesis that characterizes chronic alcohol exposure may draw choline into phospholipid biosynthesis at the expense of its use as a methyl donor. We propose that PAE increases choline needs, and that its supplementation is necessary to fulfill these competing demands for lipid and methyl use.

  PublisherOA PDFDOI

• Neonatal paw pricking alters adolescent behavior in a sex-dependent manner and sucrose partially remediates the effects

  Physiology & Behavior · 2024-09-15

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Alcohol Exposure Induces Nucleolar Stress and Apoptosis in Mouse Neural Stem Cells and Late-Term Fetal Brain

  Cells · 2024-03-02 · 11 citations

  articleOpen access

  Prenatal alcohol exposure (PAE) is a leading cause of neurodevelopmental disability through its induction of neuronal growth dysfunction through incompletely understood mechanisms. Ribosome biogenesis regulates cell cycle progression through p53 and the nucleolar cell stress response. Whether those processes are targeted by alcohol is unknown. Pregnant C57BL/6J mice received 3 g alcohol/kg daily at E8.5–E17.5. Transcriptome sequencing was performed on the E17.5 fetal cortex. Additionally, primary neural stem cells (NSCs) were isolated from the E14.5 cerebral cortex and exposed to alcohol to evaluate nucleolar stress and p53/MDM2 signaling. Alcohol suppressed KEGG pathways involving ribosome biogenesis (rRNA synthesis/processing and ribosomal proteins) and genes that are mechanistic in ribosomopathies (Polr1d, Rpl11; Rpl35; Nhp2); this was accompanied by nucleolar dissolution and p53 stabilization. In primary NSCs, alcohol reduced rRNA synthesis, caused nucleolar loss, suppressed proliferation, stabilized nuclear p53, and caused apoptosis that was prevented by dominant-negative p53 and MDM2 overexpression. Alcohol’s actions were dose-dependent and rapid, and rRNA synthesis was suppressed between 30 and 60 min following alcohol exposure. The alcohol-mediated deficits in ribosomal protein expression were correlated with fetal brain weight reductions. This is the first report describing that pharmacologically relevant alcohol levels suppress ribosome biogenesis, induce nucleolar stress in neuronal populations, and involve the ribosomal/MDM2/p53 pathway to cause growth arrest and apoptosis. This represents a novel mechanism of alcohol-mediated neuronal damage.

  PublisherOA PDFDOI

• Fetal anemia and elevated hepcidin in a mouse model of fetal alcohol spectrum disorder

  Pediatric Research · 2023-01-26 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

• Alcohol blunts pregnancy‐mediated insulin resistance and reduces fetal brain glucose despite elevated fetal gluconeogenesis, and these changes associate with fetal weight outcomes

  The FASEB Journal · 2023-09-04 · 9 citations

  articleOpen access

  Prenatal alcohol exposure (PAE) impairs fetal growth and neurodevelopment. Although alcohol is well known to alter metabolism, its impact on these processes during pregnancy is largely unexplored. Here, we investigate how alcohol affects maternal-fetal glucose metabolism using our established mouse binge model of PAE. In the dam, alcohol reduces the hepatic abundance of glucose and glycolytic intermediates, and the gluconeogenic enzymes glucose-6-phosphtase and phosphoenolpyruvate carboxykinase. Fasting blood glucose is also reduced. In a healthy pregnancy, elevated maternal gluconeogenesis and insulin resistance ensures glucose availability for the fetus. Glucose and insulin tolerance tests reveal that alcohol impairs the dam's ability to acquire insulin resistance. Alcohol-exposed dams have enhanced glucose clearance (p < .05) in early gestation, after just two days of alcohol, and this persists through late term when fetal glucose needs are maximal. However, maternal plasma insulin levels, hepatic insulin signaling, and the abundance of glucose transporter proteins remain unchanged. In the PAE fetus, the expression of hepatic gluconeogenic genes is elevated, and there is a trend for elevated blood and liver glucose levels. In contrast, fetal brain and placental glucose levels remain low. This reduced maternal fasting glucose, reduced hepatic glucose, and elevated glucose clearance inversely correlated with fetal body and brain weight. Taken together, these data suggest that alcohol blunts the adaptive changes in maternal glucose metabolism that otherwise enhance fetal glucose availability. Compensatory attempts by the fetus to increase glucose pools via gluconeogenesis do not normalize brain glucose. These metabolic changes may contribute to the impaired fetal growth and brain development that typifies PAE.

  PublisherOA PDFDOI

• Behavioral changes in FPR2/ALX and Chemr23 receptor knockout mice are exacerbated by prenatal alcohol exposure

  Frontiers in Neuroscience · 2023-07-06 · 3 citations

  articleOpen access1st authorCorresponding

  Introduction: Prenatal alcohol exposure (PAE) causes neuroinflammation that may contribute to the pathophysiology underlying Fetal Alcohol Spectrum Disorder. Supplementation with omega-3 polyunsaturated fatty acids (PUFAs) has shown success in mitigating effects of PAE in animal models, however, the underlying mechanisms are unknown. Some PUFA metabolites, specialized pro-resolving mediators (SPMs), play a role in the resolution phase of inflammation, and receptors for these are in the brain. Methods: To test the hypothesis that the SPM receptors FPR2 and ChemR23 play a role in PAE-induced behavioral deficits, we exposed pregnant wild-type (WT) and knockout (KO) mice to alcohol in late gestation and behaviorally tested male and female offspring as adolescents and young adults. Results: Maternal and fetal outcomes were not different among genotypes, however, growth and behavioral phenotypes in the offspring did differ and the effects of PAE were unique to each line. In the absence of PAE, ChemR23 KO animals showed decreased anxiety-like behavior on the elevated plus maze and FPR2 KO had poor grip strength and low activity compared to age-matched WT mice. WT mice showed improved performance on fear conditioning between adolescence and young adulthood, this was not seen in either KO. Discussion: This PAE model has subtle effects on WT behavior with lower activity levels in young adults, decreased grip strength in males between test ages, and decreased response to the fear cue indicating an effect of alcohol exposure on learning. The PAE-mediated decreased response to the fear cue was also seen in ChemR23 KO but not FPR2 KO mice, and PAE worsened performance of adolescent FPR2 KO mice on grip strength and activity. Collectively, these findings provide mechanistic insight into how PUFAs could act to attenuate cognitive impairments caused by PAE.

  PublisherOA PDFDOI

Recent grants

• Model of Fetal Alcohol Spectrum Disorder

  NIH · $2.3M · 2017–2024

• NIH Grant R01AA018693

  NIH · $1.2M · 2016

• NIH Grant R01AA006916

  NIH · $6.6M · 2016

• Experimental Factors in Fetal Alcohol Spectrum Disorder

  NIH · $1.7M · 2014–2021

Frequent coauthors

• Michael W. Miller

  Syracuse VA Medical Center

  57 shared

• Susan M. Smith

  University of North Carolina at Chapel Hill

  45 shared

• Elena I. Varlinskaya

  Binghamton University

  28 shared

• Nipun Saini

  University of North Carolina at Chapel Hill

  18 shared

• Sze Ting Kwan

  David H. Murdock Research Institute

  15 shared

• Brandon H. Presswood

  15 shared

• Dane K. Ricketts

  David H. Murdock Research Institute

  14 shared

• Frank A. Middleton

  SUNY Upstate Medical University

  14 shared

Education

• Ph.D.

  University of Otago

  1999