In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques

Abstract

One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.

Development of prefrontal cortex

“…There is a clear correlation of children with FAS and prefrontal executive functioning [ 316 ]. MRI studies showed reductions in brainstem as well as cerebellum volume in a primate FAS model and a sex-dependent change in functional connectivity and metabolism in prefrontal areas in a rat FAS model [ 317 , 318 ]. Structurally, the prefrontal cortical thickness is affected after prenatal alcohol exposure and it matures with a smaller number of excitatory neurons and more GABAergic ones disrupting the excitatory/inhibitory balance severely [ 319 – 321 ].…”

Binge-like Prenatal Ethanol Exposure Causes Impaired Cellular Differentiation in the Embryonic Forebrain and Synaptic and Behavioral Defects in Adult Mice

“…These observations indicate that GDE may cause structural defects. Indeed, the exposure of pregnant rhesus macaques to ethanol (1.5 g/kg/d) over the first 60 days of gestation resulted in significantly induced structural abnormalities in fetuses at gestational day 135, as measured by magnetic resonance image (MRI) [ 165 ]. These abnormalities were associated with the reduced excitatory, but not inhibitory, postsynaptic event amplitude in the somatosensory cortex and putamen [ 165 ], suggesting a functional significance of the structural effects of fetal alcohol exposure.…”

Impacts of Maternal Diet and Alcohol Consumption during Pregnancy on Maternal and Infant Gut Microbiota

“…Moreover, prenatal alcohol espouse was linked to changes in newborns’ cognitive and behavioral development including depression, mood diseases, and autism [ 54 , 55 ]. In utero, MRI also demonstrated [ 56 ] that maternal ethanol exposure in gestation could perturb brain development associated motor control. According to Kakiyama’s study, infants born into mothers who have alcohol consumption during pregnancy may result in hepatic damage, along with an increased number of Bacteroides [ 30 ].…”