Biomarker, neuroimaging, and genetic findings implicate the serotonin transporter (SERT) in autism spectrum disorder (ASD). Previously, we found that adult male mice expressing the autism-associated SERT Ala56 variant have altered central serotonin (5-HT) system function, as well as elevated peripheral blood 5-HT levels. Early in gestation, before midbrain 5-HT projections have reached the cortex, peripheral sources supply 5-HT to the forebrain, suggesting that altered maternal or placenta 5-HT system function could impact the developing embryo. We therefore used different combinations of maternal and embryo SERT Ala56 genotypes to examine effects on blood, placenta and embryo serotonin levels and neurodevelopment at embryonic day E14.5, when peripheral sources of 5-HT predominate, and E18.5, when midbrain 5-HT projections have reached the forebrain. Maternal SERT Ala56 genotype was associated with decreased placenta and embryonic forebrain 5-HT levels at E14.5. Low 5-HT in the placenta persisted, but forebrain levels normalized by E18.5. Maternal SERT Ala56 genotype effects on forebrain 5-HT levels were accompanied by a broadening of 5-HT-sensitive thalamocortical axon projections. In contrast, no effect of embryo genotype was seen in concepti from heterozygous dams. Blood 5-HT levels were dynamic across pregnancy and were increased in SERT Ala56 dams at E14.5. Placenta RNA sequencing data at E14.5 indicated substantial impact of maternal SERT Ala56 genotype, with alterations in immune and metabolic-related pathways. Collectively, these findings indicate that maternal SERT function impacts offspring placental 5-HT levels, forebrain 5-HT levels, and neurodevelopment.

Purpose Brief, high-intensity cycling is popular because physiological benefits accrue with a short workout time, but burning pain in the quadriceps is a potential barrier to engaging in this type of exercise. Virtual reality (VR) can temporarily decrease pain, but its effect on muscle pain during high-intensity exercise is unknown. The primary purpose of this experiment was to test whether adding interactive VR (I-VR) to high-intensity cycling could reduce quadriceps pain or improve performance. Methods Ninety-four adults who were physically active in their leisure time and age 18 to 29 yr completed three 30-s sprint interval cycling trials at a high resistance (0.085- and 0.075-kg resistance to the flywheel per kilogram body weight for men and women, respectively). In this randomized between-subject experiment, participants cycled while wearing a head-mounted display and viewing either (i) a dynamically changing cityscape perceived as interactively cycling through a virtual city (I-VR group) or (ii) a static picture of the cityscape with instructions to mentally imagine cycling through that city (static VR/motor imagery control group). Results Sphericity-adjusted 2 × 3 (group–time) ANOVA revealed a significant group–time interaction (F = 4.568; df = 1.499, 133.301; η p 2 = 0.047, P = 0.021) for pain intensity. With I-VR, pain intensities were 13.3% (mean, 4.60 vs 5.31; d = 0.28) and 11.8% (mean, 5.68 vs 6.44; d = 0.27) lower at sprint trials 2 and 3, respectively. The group–time interaction (P = 0.412) was not significant for total work. Conclusion Compared with a static VR/motor imagery control condition, I-VR during brief, high-intensity, fatigue-inducing leg cycling attenuates quadriceps pain intensity without reducing performance.

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