Linking prenatal alcohol-induced transcriptomic alterations to hippocampal-associated structural and behavioral...

Prenatal alcohol exposure can have a lasting and devastating impact on the hippocampus. Structural deficits including volumetric loss, shape changes, and microstructural abnormalities are observed in clinical patients with Fetal Alcohol Spectrum Disorders (FASD) and in preclinical models. In addition, in utero alcohol exposure is associated with cognitive and behavioral impairments related to hippocampal dysfunction, including spatial and contextual memory deficits. This review discusses the cellular, genetic, and epigenetic changes caused by alcohol during early hippocampal development that contribute to long-term damage and dysfunction. By synthesizing current evidence from human patients and preclinical models, specific behavioral and neuroanatomical deficits caused by alcohol exposure can be linked to precise molecular changes in prenatal development. Specifically, certain biological functions have been repeatedly identified as mechanisms of alcohol-related damage and will be discussed in relation to hippocampal development and function: neurogenesis and neuronal differentiation, apoptosis, induction of oxidative stress, neuroinflammation, and compromised synaptogenesis and synaptic plasticity. This review seeks to connect early developmental vulnerabilities to later life phenotypes of hippocampal damage to support the discovery of prenatal alcohol exposure biomarkers and the development of potential therapeutics for alcohol-related impairments.