Dataset Information

Combined Face-Brain Morphology and Associated Neurocognitive Correlates in Fetal Alcohol Spectrum Disorders.

ABSTRACT: BACKGROUND:Since the 1970s, a range of facial, neurostructural, and neurocognitive adverse effects have been shown to be associated with prenatal alcohol exposure. Typically, these effects are studied individually and not in combination. Our objective is to improve the understanding of the teratogenic effects of prenatal alcohol exposure by simultaneously considering face-brain morphology and neurocognitive measures. METHODS:Participants were categorized as control (n = 47), fetal alcohol syndrome (FAS, n = 22), or heavily exposed (HE) prenatally, but not eligible for a FAS diagnosis (HE, n = 50). Structural brain MRI images and high-resolution 3D facial images were analyzed using dense surface models of features of the face and surface shape of the corpus callosum (CC) and caudate nucleus (CN). Asymmetry of the CN was evaluated for correlations with neurocognitive measures. RESULTS:(i) Facial growth delineations for FAS, HE, and controls are replicated for the CN and the CC. (ii) Concordance of clinical diagnosis and face-based control-FAS discrimination improves when the latter is combined with specific brain regions. In particular, midline facial regions discriminate better when combined with a midsagittal profile of the CC. (iii) A subset of HE individuals was identified with FAS-like CN dysmorphism. The average of this HE subset was FAS-like in its facial dysmorphism. (iv) Right-left asymmetry found in the CNs of controls is not apparent for FAS, is diminished for HE, and correlates with neurocognitive measures in the combined FAS and HE population. CONCLUSIONS:Shape analysis which combines facial regions with the CN, and with the CC, better identify those with FAS. CN asymmetry was reduced for FAS compared to controls and is strongly associated with general cognitive ability, verbal learning, and recall in those with prenatal alcohol exposure. This study further extends the brain-behavior relationships known to be vulnerable to alcohol teratogenesis.

SUBMITTER: Suttie M

PROVIDER: S-EPMC6120799 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Combined Face-Brain Morphology and Associated Neurocognitive Correlates in Fetal Alcohol Spectrum Disorders.

Suttie Michael M Wozniak Jeffrey R JR Parnell Scott E SE Wetherill Leah L Mattson Sarah N SN Sowell Elizabeth R ER Kan Eric E Riley Edward P EP Jones Kenneth L KL Coles Claire C Foroud Tatiana T Hammond Peter P

Alcoholism, clinical and experimental research 20180720 9

<h4>Background</h4>Since the 1970s, a range of facial, neurostructural, and neurocognitive adverse effects have been shown to be associated with prenatal alcohol exposure. Typically, these effects are studied individually and not in combination. Our objective is to improve the understanding of the teratogenic effects of prenatal alcohol exposure by simultaneously considering face-brain morphology and neurocognitive measures.<h4>Methods</h4>Participants were categorized as control (n = 47), fetal ...[more]

PMID: 29935097

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Project description:The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination. Recent studies have shed light on the molecular mechanisms underlying these white matter abnormalities. Rodent models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor cells. Ethanol exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological specimens. Several studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system, including multiple sclerosis and fetal alcohol syndrome. Acute ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues, while ethanol increased the expression of tumor necrosis factor α in mouse and human neurons. White matter lesions have been induced in the developing sheep brain by alcohol exposure in early gestation. Rat fetal alcohol syndrome models have shown reduced axon diameters, with thinner myelin sheaths, as well as reduced numbers of oligodendrocytes, which were also morphologically aberrant oligodendrocytes. Expressions of markers for mature myelination, including myelin basic protein, also were reduced. The accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal development. Future studies using fetal oligodendrocyte- and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in adulthood. By combining various imaging modalities with molecular studies, it may be possible to determine which fetuses are at risk and to intervene therapeutically early in the pregnancy.

Project description:Fetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD model.Pregnant rats were orogastrically treated daily with alcohol (4.5 g/kg, gestational day [GD] 5 to 10; 6.0 g/kg, GD 11 to 19) or 50% maltose dextrin (isocalorically matched pair-fed controls). On GD 20, placentae were collected, flash-frozen, and stored until tissues were homogenized. Protein lysates were denatured, reduced, captured on a 10-kDa spin filter, and digested. Peptides were eluted, reconstituted, and analyzed by a Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometer.Mass spectrometry (MS) analysis identified 2,285 placental proteins based on normalized spectral counts and 2,000 proteins by intensity-based absolute quantification. Forty-five placental proteins were significantly (p < 0.05) altered by gestational alcohol exposure by both quantification approaches. These included proteins directly related to alcohol metabolism; specific isoforms of alcohol dehydrogenase and aldehyde dehydrogenase were up-regulated in the alcohol group. Ingenuity analysis identified ethanol degradation as the most significantly altered canonical pathway in placenta, and fetal/organ development as most altered function, with increased risk for metabolic, neurological, and cardiovascular diseases. Physiological roles of the significantly altered proteins were related to early pregnancy adaptations, implantation, gestational diseases, fetal organ development, neurodevelopment, and immune functions.We conclude that the placenta is a valuable organ not only to understand FASD etiology but it may also serve as a diagnostic tool to identify novel biomarkers for detecting the outcome of fetal alcohol exposure. Placental MS analysis can offer sophisticated insights into identifying alcohol metabolism-related enzymes and regulators of fetal development.

Dataset Information

Combined Face-Brain Morphology and Associated Neurocognitive Correlates in Fetal Alcohol Spectrum Disorders.

Publications

Combined Face-Brain Morphology and Associated Neurocognitive Correlates in Fetal Alcohol Spectrum Disorders.

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