Sex-specific alterations in cognitive control following moderate prenatal alcohol exposure and transient systemic hypoxia ischemia in the rat

Authors

Brooke R Dunn, Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
Sarah L Olguin, Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
Suzy Davies, Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
Nathaniel G Pavlik, Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
Jonathan L Brigman, Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA; Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA
Derek Hamilton, Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA; Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA
Daniel D Savage, Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
Jessie R Maxwell, Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA; Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Document Type

Article

Publication Date

2-1-2024

Abstract

BACKGROUND: Prenatal alcohol exposure (PAE) continues to be a worldwide problem. Affected offspring display impaired neurodevelopment, including difficulties with executive control. Although PAE has also been associated with decreased blood flow to fetuses, the relationship between PAE and altered blood flow is not well understood.

METHODS: We used preclinical models of PAE, transient systemic hypoxia ischemia (TSHI), and PAE + TSHI combined to assess the effects on neurodevelopmental outcomes using translationally relevant touchscreen operant platform testing. Twenty-eight Long-Evans (Blue Spruce, Strain HsdBlu:LE) dams were randomly assigned to one of four experimental groups: Saccharin Control (Sham), 5% Ethanol (PAE), TSHI, or 5% Ethanol and TSHI (PAE + TSHI). Dams consumed either saccharin or 5% ethanol during gestation. TSHI was induced on Embryonic Day 19 (E19) during an open laparotomy where the uterine arteries were transiently occluded for 1 h. Pups were born normally and, after weaning, were separated by sex. A total of 80 offspring, 40 males and 40 females, were tested on the 5-Choice Continuous Performance paradigm (5C-CPT).

RESULTS: Female offspring were significantly impacted by TSHI, but not PAE, with an increase in false alarms and a decrease in hit rates, omissions, accuracy, and correct choice latencies. In contrast, male offspring were mildly affected by PAE, but not TSHI, showing decreases in premature responses and increases in accuracy. No significant interactions between PAE and TSHI were detected on any measure.

CONCLUSION: Transient systemic hypoxia ischemia impaired performance on the 5C-CPT in females, leading to a bias toward stimulus responsivity regardless of stimulus type. In contrast, TSHI did not affect male offspring, and only slight effects of PAE were seen. Together, these data suggest that TSHI in females may cause alterations in cortical structures that override alterations caused by moderate PAE.

Publication Title

Alcohol Clin Exp Res (Hoboken)

ISSN

2993-7175

DOI

10.1111/acer.15276

Recommended Citation

Dunn BR, Olguin SL, Davies S, Pavlik NG, Brigman JL, Hamilton D, Savage DD, Maxwell JR. Sex-specific alterations in cognitive control following moderate prenatal alcohol exposure and transient systemic hypoxia ischemia in the rat. Alcohol Clin Exp Res (Hoboken). 2024 Feb 1. doi: 10.1111/acer.15276. Epub ahead of print. PMID: 38302722.