White matter abnormalities in fetal alcohol spectrum disorders: Focus on axon growth and guidance

Mathews, Erin; Dewees, Kevyn; Diaz, Deborah; Favero, Carlita B.

doi:10.1177/1535370220980398

Cited by 10 publications

(5 citation statements)

References 86 publications

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“…The result of increased callosal size may be interpreted by following the concept that PAE results in a delay in synaptic pruning, abnormal axon guidance, and subsequently altered neuronal connectivity ( Mathews et al. 2021 ), detectable as early structural and volumetric alterations in the trajectory of callosal growth.…”

Section: Discussionmentioning

confidence: 99%

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure

et al. 2023

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Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini–Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P ≤ 0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1–3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

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Section: Discussionmentioning

confidence: 99%

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure

et al. 2023

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Section: Descriptionmentioning

confidence: 99%

“…There is very little research into effects of PAE on growth and guidance of axon populations (our current understanding reviewed in 11 , but several studies provide evidence these processes may be affected. Minciacchi et al 12 show that the cortical zone that receives thalamocortical axons is thinner in ethanol-exposed rats, and that thalamo-cortical termination is abnormal in the cortex.…”

Section: Descriptionmentioning

confidence: 99%

Prenatal alcohol exposure alters axon formation and Robo/Slit guidance cue expression in the internal capsule at E15.5

Chi

Dewees

Scoville

et al. 2022

Preprint

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We previously showed the prenatal alcohol exposure (PAE) induced precocious growth of E15.5 internal capsule axons. We set out to further delineate which axon tracts were affected and a potential mechanism for this phenomenon. Pregnant Swiss Webster mice were exposed to saline or 20% ethanol via subcutaneous injection from embryonic days (E) 7.5 until E14.5. E15.5 embryos were captured via C-section and brains were either fixed for immunostaining or flash frozen for tissue punches. To identify internal capsule axons we performed immunohistochemistry using L1 antibody to visualize all internal capsule axons and NetrinG1 antibody to identify thalamocortical axons specifically. mRNA was extracted from tissue punches to visualize Slit1, Robo1, Slit2, and Robo2 gene expression levels via real time RT PCR. We found that L1-expressing axons exhibited increased axon crossing in females with the opposite effect in males and no difference in Netrin-G1-expressing axons. We also found PAE increased Robo1 mRNA. Taken together, our results indicate that PAE elicits specific effects on axon trajectories, potentially via the Slit/Robo guidance family of repellents and receptors. These findings add to the growing body of evidence demonstrating alcohol disruptions of axon growth and guidance during embryonic development that may contribute to connectivity errors that characterize Fetal Alcohol Spectrum Disorders.

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“…Molecular mechanisms remained unclear. In the developing brain, alcohol impairs gene expression of the guidance cue and receptor families required for axon growth [66].…”

Section: Pathogenetic Mechanismmentioning

confidence: 99%

Ignored Papers, Invented Quotations: A History of Fetal Alcohol Syndrome

Obladen¹

2021

Neonatology

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Given the high rate of alcoholism throughout history, its effects on the fetus may have existed for millennia. But, the claim that Greeks and Romans were aware of fetal alcohol syndrome rests on incorrect citations. From 1725, maternal alcohol consumption was associated with retarded fetal growth and neurological anomalies. From 1809, scientists followed Lamarck’s theory that the disorders parents acquire during their lifetime are passed on to their offspring. Fetal effects were thought to be inherited mainly from the father. During the 19th century, parental alcoholism became associated with malformations. In 1915, Ballantyne distinguished genetic influence via germ cells from toxin’s effect on the embryo. Fetal alcohol syndrome was characterized by Rouquette [Influence de la toxicomanie alcoolique parentale sur le développement physique et psychique des jeunes enfants] in 1957 and Lemoine et al. [Ouest Medical. 1968;21:476–482] in 1968 as consisting of 4 features: (A) facial anomalies (narrow forehead, retracted upper lip, and cupped ears), (B) severe growth retardation (prenatal and postnatal), (C) malformations (limbs, cardiac, and visceral), and (D) central nervous system anomalies (hyperexcitability and mental retardation). But, their studies, written in French, remained disregarded. In 1973, Jones et al. [Lancet. 1973;302:999–1001] reported “the first association between maternal alcoholism and aberrant morphogenesis in the offspring.” The history of fetal alcohol syndrome reveals shortcomings in citation practice. Alleged quotations remained unverified, non-English publications neglected, and short quotations taken out of context. Prejudiced by religious and abstinence groups, reports on alcohol damage to the unborn were fraught with emotions, moralizing, social implications, and presentism, the interpretation of past events with present knowledge.

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White matter abnormalities in fetal alcohol spectrum disorders: Focus on axon growth and guidance

Cited by 10 publications

References 86 publications

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure

Prenatal alcohol exposure alters axon formation and Robo/Slit guidance cue expression in the internal capsule at E15.5

Ignored Papers, Invented Quotations: A History of Fetal Alcohol Syndrome

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