Fetal alcohol exposure impairs learning and memory functions and elevates levels of various biochemical markers of Alzheimer's disease in the brain of 12-month-old rats

Alcohol Clin Exp Res (Hoboken). 2023 May;47(5):882-892. doi: 10.1111/acer.15061. Epub 2023 Apr 15.

Abstract

Background: Alcohol drinking during pregnancy often adversely affects brain development among offspring, inducing persistent central nervous system dysfunction. However, it is unknown whether fetal alcohol exposure (FAE) promotes the biochemical characteristics of Alzheimer's disease in offspring.

Methods: We used a first- and second-trimester human equivalent rat model of FAE that involves feeding a liquid diet containing 6.7% v/v ethanol from gestational days 7 through 21 in Fischer-344 rats. Control rats were fed an isocaloric liquid diet or rat chow ad libitum. Pups were weaned on postnatal day 21 and housed by sex. They were used for behavioral and biochemical studies at about 12 months of age. Only one male or one female offspring from a litter was included in each experimental group.

Results: Fetal alcohol-exposed offspring had poorer learning and memory functions than controls. The experimental animals, both male and female, also had elevated levels of acetylcholinesterase (AChE) activity, hyperphosphorylated-tau protein, β-amyloid (Aβ) and Aβ1-42 proteins, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and Unc-5 netrin receptor C (UNC5C) proteins in the cerebral cortex and hippocampus at 12 months of age.

Conclusions: These findings show that FAE increases the expression of some of the biochemical and behavioral phenotypes of Alzheimer's disease.

Keywords: Alzheimer's disease-related proteins; acetylcholinesterase; fetal alcohol; memory.