Prenatal ethanol exposure enhances the susceptibility to depressive behavior of adult offspring rats fed a high-fat diet by affecting BDNF-associated pathway

Epidemiological studies have shown that exposure to ethanol during pregnancy can result in an increased risk for depression in offspring. A 'brain-derived neurotrophic factor (BDNF) hypothesis' has been proposed to help explain the pathogenic mechanism of depression. This study was designed to verify the enhanced susceptibility to depression in prenatal ethanol exposure (PEE) offspring rats and explore possible intrauterine programming mechanisms related to the BDNF signaling pathway. Pregnant rats were intragastrically administrated ethanol (4 g/kg/day) from gestational day 11 until term delivery. All offspring rats were given a high-fat diet after weaning. Then the behavior tests, including sucrose preference test and open field test, were performed to adult offspring rats. The histomorphology of hippocampus was examined, and the expression of genes related to the BDNF signaling pathway was detected in the hippocampus of PEE offspring. The PEE female adult offspring rats showed depression-like behavior, with obvious morphological injury in hippocampus. Additionally, the mRNA expression levels of glucocorticoid receptor (GR) and BDNF pathway-associated genes were changed in hippocampus. Multigene RT-qPCR also revealed that the mRNA expression levels for BDNF pathway-associated genes and synaptic plasticity genes were decreased in the hippocampus of fetal offspring rats in the PEE group. The underlying mechanism involves an increased GR expression that constantly suppresses the BDNF signaling pathway, and aggravates the functional insult to the hippo-campus, resulting in an increased susceptibility to depression among PEE female adult offspring rats. Results of the present study provide theoretical and experimental evidence that can be used for the early prevention and treatment of depression.