Effects of all three trimester moderate binge alcohol exposure on the foetal hippocampal formation and olfactory bulb

Abstract

Objective Pre-natal alcohol exposure results in injury to the hippocampus and olfactory bulb, but currently there is no consensus on the critical window of vulnerability. This study tested the hypothesis that pre-natal exposure to a moderate dose of alcohol during all three trimester-equivalents alters development of the hippocampal formation and olfactory bulb in an ovine model, where all brain development occurs pre-natally as it does in humans. Research design and methods Pregnant sheep were divided into saline control and a binge drinking groups (alcohol dose 1.75 g kg−1; mean peak blood alcohol concentration 189 + 19mg dl−1). Outcome and results The density, volume and total cell number were not different between groups for the dentate gyrus, pyramidal cells in the CA1 and CA2/3 fields and mitral cells in the olfactory bulb. Conclusions A moderate dose of alcohol administered in a binge pattern throughout gestation does not alter cell numbers in the hippocampus or olfactory bulb and exposure during the third trimester-equivalent is required for hippocampal injury, unless very high doses of alcohol are administered. This has important implications in establishing the sensitivity of imaging modalities such as MRI in which volumetric measures are being studied as biomarkers for pre-natal alcohol exposure.

PLGF, a placental marker of fetal brain defects after in utero alcohol exposure

“…Determining prenatal alcohol exposure is crucial to identify the children/population at risk, but it is not realistic to assess all infants with prenatal alcohol exposure. First, a “safe” dose of alcohol is controversial and highly debated [ 16 , 33 ]; second, patterns of alcohol consumption differ (chronic/acute) and their effect on the fetus is not the same [ 10 ]; and third, the developing brain has windows of vulnerability during which potential harm is greater [ 25 , 49 ]. These limits also contribute to the discrepancies between different cohort studies on the impact of alcohol consumption on the infant [ 26 , 31 , 45 ].…”

Substance Use in the Perinatal Period

“…Alcohol-related fetal and pregnancy outcomes and the severity thereof can vary depending on the timing of exposure; that is, effects linked with first trimester exposure [83] may be different from those associated with the second [84-86] or third trimester [87,88], and these in turn may differ from outcomes due to persistent use throughout the duration of pregnancy [89]. For example, alcohol consumption has been associated with oral clefts [83] during the first-trimester [83], adverse effects on rat brain weight during the second [84], and disruptions in rat neuroimmune systems [88].…”

Prenatal alcohol exposure and developmental programming of mental illness

“…Cudd and colleagues have further demonstrated changes in molecular pathways associated with the development of mental illness. Utilising the Suffolk sheep model, they treated dams with 1.75 g/kg ethanol intravenously, resulting in a BAL of 189 ± 19 mg/ dL, and demonstrated changes within offspring hippocampus including density and volume of dentate gyrus granular cells and cerebellar Purkinje cell loss 152,153 . This group also observed significant changes to the HPA axis within the foetus, including increased circulating cortisol and adrenocorticotropic hormone 154 .…”