Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

Autor: Hornburg KJ; Department of Radiology, School of Medicine, Duke University, Durham, North Carolina, USA., Slosky LM; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina, USA.; Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA., Cofer G; Department of Radiology, School of Medicine, Duke University, Durham, North Carolina, USA., Cook J; Department of Radiology, School of Medicine, Duke University, Durham, North Carolina, USA., Qi Y; Department of Radiology, School of Medicine, Duke University, Durham, North Carolina, USA., Porkka F; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina, USA., Clark NB; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina, USA., Pires A; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina, USA., Petrella JR; Department of Radiology, School of Medicine, Duke University, Durham, North Carolina, USA., White LE; Department of Neurology, School of Medicine, Duke University, Durham, North Carolina, USA., Wetsel WC; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina, USA.; Department of Neurology, School of Medicine, Duke University, Durham, North Carolina, USA.; Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, North Carolina, USA., Barak L; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina, USA., Caron MG; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina, USA.; Department of Neurology, School of Medicine, Duke University, Durham, North Carolina, USA., Johnson GA; Department of Radiology, School of Medicine, Duke University, Durham, North Carolina, USA.; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina, USA.
Jazyk: angličtina
Zdroj: NMR in biomedicine [NMR Biomed] 2023 Feb; Vol. 36 (2), pp. e4842. Date of Electronic Publication: 2022 Nov 23.
DOI: 10.1002/nbm.4842
Abstrakt: The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 μm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: