MIRI investigator Dr. Elizabeth Yen, received the 2021 Outstanding Young Investigator Award from the International Behavioural and Neural Genetics Society (IBANGS). Her research titled "The Role of Sex and Inflammation on the Developing Brain in Neonatal Abstinence Syndrome" was also selected for a talk at the "Neonatal Opioid Withdrawal Syndrome in Mice and Humans" Symposium in the annual 22nd Annual Genes, Brain, and Behavior Meeting organized by IBANGS.
Read the abstract for the talk below.
Sex-specific Reward Modulation and Inflammatory Impact of Prenatal Opioid Exposure on the Developing Brain
Elizabeth Yen1,2, Tomoko Kaneko-Tarui2, Neel Madan1, Samuel Carpenter3, Alice Graham3, Tomo Tarui1,2, Jonathan Davis1, Jill Maron1,2
1 Department of Pediatrics, Tufts University School of Medicine, Tufts Children’s Hospital, Boston, USA
2 Mother Infant Research Institute, Tufts Medical Center, Boston, USA
3 Department of Psychiatry, Oregon and Health Science University, Portland, USA
Opioid-exposed males are at risk of developing severe withdrawal called neonatal abstinence syndrome (NAS) and require pharmacotherapy (NAS-Tx). The underlying mechanism for this sex-specific risk is unknown. Our laboratory showed that males with NAS-Tx had significantly higher expression of DRD2 (key reward gene) than females, evidence that heightened reward signaling may play a sex-specific role in the severity of NAS. Emerging animal data show that inflammation may modulate the reward property of opioids. Opioid binding to TLR4 on glial cells creates an inflammatory cascade that reinforces its reward/addictive properties with deleterious effects on cognition. Using saliva and brain MRI we aim to understand the potential sex-specific impact of prenatal opioids on pro-inflammatory pathways and the developing brain. Saliva samples collected within 48 hours of birth from 16 neonates with NAS and 16 sex- and age-matched non-exposed controls underwent transcriptomic analyses of IL1B, IL6, TNFα, CXCL1, MCP1 IL10, and DRD2. Compared to controls, neonates with NAS had a 3-fold expression of IL6 and MCP1, with even higher expression (5-fold) in NAS-Tx (p≤0.05). Females with NAS-Tx had a 4-fold expression of IL1B, IL6, MCP1, and downregulation of IL10 than males (p≤0.05); expression of IL6 and MCP1 correlated with DRD2 (r=0.99, p<0.05). Structural MRI showed white matter hyperintensity in four of five females with NAS. All controls had normal MRIs. Functional MRI is ongoing. Prenatal opioids modulate inflammation and reward signaling in a sex-specific manner. Whether prenatal opioids contribute to the white matter changes on the developing brain is subject to further studies.
Funded by: Natalie V. Zucker Research Center for Women’s Scholars Grant, K12 BIRCWH Grant (5K12HD092535-04), Charles H. Hood Foundation Child Health Research Award