Regional Patterns of Alcohol-Induced Neuronal Loss Depend on Genetics: Implications for Fetal Alcohol Spectrum Disorder.

BACKGROUND: Alcohol exposure during pregnancy can kill developing neurons and lead to fetal alcohol spectrum disorder (FASD). However, affected individuals differ in their regional patterns of alcohol-induced neuropathology. Because neuroprotective genes are expressed in spatially selective ways, their mutation could increase the vulnerability of some brain regions, but not others, to alcohol teratogenicity. The objective of this study was to determine whether a null mutation of neuronal nitric oxide synthase (nNOS) can increase the vulnerability of some brain regions, but not others, to alcohol-induced neuronal losses. METHODS: Immunohistochemistry identified brain regions in which nNOS is present or absent throughout postnatal development. Mice genetically deficient for nNOS (nNOS-/- ) and wild-type controls received alcohol (0.0, 2.2, or 4.4 mg/g/d) over postnatal days (PD) 4 to 9. Mice were sacrificed in adulthood (~PD 115), and surviving neurons in the olfactory bulb granular layer and brain stem facial nucleus were quantified stereologically. RESULTS: nNOS was expressed throughout postnatal development in olfactory bulb granule cells but was never expressed in the facial nucleus. In wild-type mice, alcohol reduced neuronal survival to similar degrees in both cell populations. However, null mutation of nNOS more than doubled alcohol-induced cell death in the olfactory bulb granule cells, while the mutation had no effect on the facial nucleus neurons. As a result, in nNOS-/- mice, alcohol caused substantially more cell loss in the olfactory bulb than in the facial nucleus. CONCLUSIONS: Mutation of the nNOS gene substantially increases vulnerability to alcohol-induced cell loss in a brain region where the gene is expressed (olfactory bulb), but not in a separate brain region, where the gene is not expressed (facial nucleus). Thus, differences in genotype may explain why some individuals are vulnerable to FASD, while others are not, and may determine the specific patterns of neuropathology in children with FASD.

Neuropsychological Profiles of Athletes and Views of Parents Choosing Flag Versus Tackle Football Participation.

Background: Previous studies have found that injury rates are slightly higher in children who play flag football versus tackle football. It is unclear if this difference is due to the way each type is played or taught or whether there are intrinsic differences in attitudes or neuropsychological characteristics in children and their parents. Purpose: To determine whether children who play flag football score differently from those who play tackle football on validated neuropsychological tests. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Each participating athlete (aged 8-12 years) was recruited in 2018 and 2019 by email through local youth football leagues and the local university. Each athlete was administered a 1-time multidimensional assessment battery. The battery included the Wechsler Abbreviated Scale of Intelligence-2nd Edition, the children's version of the Trail Making Test, the Integrated Digit Span and Spatial Span subtests of the Wechsler Intelligence Scale for Children-4th Edition (WISC-IV), and the Beck Self-Concept Inventory for Youth. The parent/guardian of each athlete completed the Achenbach Child Behavior Checklist-Parent Report Form, the Behavior Rating Inventory of Executive Function (BRIEF)-Parent Form, and a custom survey. These tests were used to determine IQ estimates and standardized scores, measuring verbal comprehension, matrix reasoning, mental set-shifting, attention, cognitive processing speed, working memory, spatial processing, perception of self-concept, behavioral regulation index, metacognition index, and global executive composite. Scores were compared between flag football and tackle football groups by 2-sample t test, with the Wilcoxon rank-sum test used for nonparametric data. Results: A total of 64 athletes (41 tackle football, 23 flag football) were enrolled from youth football leagues (grades 4-6). Flag players scored significantly higher on the WISC-IV Spatial Span-Backward subtest (scaled mean, 12.0 vs 10.6; P = .046), while tackle players had significantly higher BRIEF-Inhibit subscores (mean t-score, 45 vs 42; P = .026). There were no significant differences in any of the other tests, including socioeconomic status and perceived concussion risks. Conclusion: Concerns that injury epidemiologic studies comparing flag with tackle football could be confounded by intrinsic differences in the children who choose to play each type seem to be unfounded.