Developing Brain Glucose Transporters, Serotonin, Serotonin Transporter, and Oxytocin Receptor Expression in Response to Early-Life Hypocaloric and Hypercaloric Dietary, and Air Pollutant Exposures

• Published in: Developmental neuroscience Vol. 43; no. 1; pp. 27 - 42
• Main Authors: Ye, Xin, Shin, Bo-Chul, Baldauf, Claire, Ganguly, Amit, Ghosh, Shubhamoy, Devaskar, Sherin U.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.01.2021
• Subjects: Air Pollutants; Animals; Brain; Diet; Female; Glucose Transport Proteins, Facilitative; Glucose Transporter Type 1; Glucose Transporter Type 3; Male; Mice; Oxytocin; Pregnancy; Receptors, Oxytocin; Research Article; Serotonin; Serotonin Plasma Membrane Transport Proteins; Neurodevelopment; Environmental exposure; Intrauterine growth restriction; Neurotransmitters; Fetal brain
• DOI: 10.1159/000514709
• ISSN: 0378-5866

Perturbed maternal diet and prenatal exposure to air pollution (AP) affect the fetal brain, predisposing to postnatal neurobehavioral disorders. Glucose transporters (GLUTs) are key in fueling neurotransmission; deficiency of the neuronal isoform GLUT3 culminates in autism spectrum disorders. Along with the different neurotransmitters, serotonin (5-HT) and oxytocin (OXT) are critical for the development of neural connectivity. Serotonin transporter (SERT) modulates synaptic 5-HT levels, while the OXT receptor (OXTR) mediates OXT action. We hypothesized that perturbed brain GLUT1/GLUT3 regulated 5-HT-SERT imbalance, which serves as a contributing factor to postnatal neuropsychiatric phenotypes, with OXT/OXTR providing a counterbalance. Employing maternal diet restriction (intrauterine growth restriction [IUGR]), high-fat (HF) dietary modifications, and prenatal exposure to simulated AP, fetal (E19) murine brain 5-HT was assessed by ELISA with SERT and OXTR being localized by immunohistochemistry and measured by quantitative Western blot analysis. IUGR with lower head weights led to a 48% reduction in male and female fetal brain GLUT3 with no change in GLUT1, when compared to age- and sex-matched controls, with no significant change in OXTR. In addition, a ∼50% (p = 0.005) decrease in 5-HT and SERT concentrations was displayed in fetal IUGR brains. In contrast, despite emergence of microcephaly, exposure to a maternal HF diet or AP caused no significant changes. We conclude that in the IUGR during fetal brain development, reduced GLUT3 is associated with an imbalanced 5-HT-SERT axis. We speculate that these early changes may set the stage for altering the 5HT-SERT neural axis with postnatal emergence of associated neurodevelopmental disorders.