TY - JOUR
T1 - Angiogenic gene networks are dysregulated in opioid use disorder
T2 - evidence from multi-omics and imaging of postmortem human brain
AU - Mendez, Emily F.
AU - Wei, Haichao
AU - Hu, Ruifeng
AU - Stertz, Laura
AU - Fries, Gabriel R.
AU - Wu, Xizi
AU - Najera, Katherine E.
AU - Monterey, Michael D.
AU - Lincoln, Christie M.
AU - Kim, Joo won
AU - Moriel, Karla
AU - Meyer, Thomas D.
AU - Selvaraj, Sudhakar
AU - Teixeira, Antonio L.
AU - Zhao, Zhongming
AU - Xu, Junqian
AU - Wu, Jiaqian
AU - Walss-Bass, Consuelo
N1 - Funding Information:
We are grateful for the invaluable donations and participation from families, as well as for the generous collaboration of the medical examiners at the Harris County Institute of Forensic Sciences. This study was supported by R01DA044859 to CWB. ZZ was supported by R01LM012806. The University of Texas System provided funding for the Neuropsychiatric Proteome Database, for which proteomics data from brain tissue was generated by the Mass Spectrometry Core at the University of Texas Medical Branch.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/12
Y1 - 2021/12
N2 - Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose. Using next-generation RNA sequencing and proteomics techniques, we identified 394 differentially expressed (DE) coding and long noncoding (lnc) RNAs as well as 213 DE proteins in Brodmann Area 9 of OUD subjects. The RNA and protein changes converged on pro-angiogenic gene networks and cytokine signaling pathways. Four genes (LGALS3, SLC2A1, PCLD1, and VAMP1) were dysregulated in both RNA and protein. Dissecting these DE genes and networks, we found cell type-specific effects with enrichment in astrocyte, endothelial, and microglia correlated genes. Weighted-genome correlation network analysis (WGCNA) revealed cell-type correlated networks including an astrocytic/endothelial/microglia network involved in angiogenic cytokine signaling as well as a neuronal network involved in synaptic vesicle formation. In addition, using ex vivo magnetic resonance imaging, we identified increased vascularization in postmortem brains from a subset of subjects with OUD. This is the first study integrating dysregulation of angiogenic gene networks in OUD with qualitative imaging evidence of hypervascularization in postmortem brain. Understanding the neurovascular effects of OUD is critical in this time of widespread opioid use.
AB - Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose. Using next-generation RNA sequencing and proteomics techniques, we identified 394 differentially expressed (DE) coding and long noncoding (lnc) RNAs as well as 213 DE proteins in Brodmann Area 9 of OUD subjects. The RNA and protein changes converged on pro-angiogenic gene networks and cytokine signaling pathways. Four genes (LGALS3, SLC2A1, PCLD1, and VAMP1) were dysregulated in both RNA and protein. Dissecting these DE genes and networks, we found cell type-specific effects with enrichment in astrocyte, endothelial, and microglia correlated genes. Weighted-genome correlation network analysis (WGCNA) revealed cell-type correlated networks including an astrocytic/endothelial/microglia network involved in angiogenic cytokine signaling as well as a neuronal network involved in synaptic vesicle formation. In addition, using ex vivo magnetic resonance imaging, we identified increased vascularization in postmortem brains from a subset of subjects with OUD. This is the first study integrating dysregulation of angiogenic gene networks in OUD with qualitative imaging evidence of hypervascularization in postmortem brain. Understanding the neurovascular effects of OUD is critical in this time of widespread opioid use.
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U2 - 10.1038/s41380-021-01259-y
DO - 10.1038/s41380-021-01259-y
M3 - Article
C2 - 34385598
AN - SCOPUS:85112678914
SN - 1359-4184
VL - 26
SP - 7803
EP - 7812
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 12
ER -