1. Angiogenic gene networks are dysregulated in opioid use disorder: evidence from multi-omics and imaging of postmortem human brain
- Author
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Gabriel Rodrigo Fries, Emily Mendez, Junqian Xu, Zhongming Zhao, Sudhakar Selvaraj, Jia Qian Wu, Joo Won Kim, Thomas Meyer, Katherine Najera, Xizi Wu, Consuelo Walss-Bass, Laura Stertz, Christie M. Lincoln, Haichao Wei, Ruifeng Hu, Antônio Lúcio Teixeira, Karla Moriel, and Michael D Monterey
- Subjects
Proteomics ,Gene regulatory network ,Biology ,Cellular and Molecular Neuroscience ,medicine ,Humans ,Gene Regulatory Networks ,Molecular Biology ,Gene ,VAMP1 ,Microglia ,Neovascularization, Pathologic ,RNA ,Brain ,High-Throughput Nucleotide Sequencing ,Human brain ,Opioid-Related Disorders ,Psychiatry and Mental health ,medicine.anatomical_structure ,Cytokines ,RNA, Long Noncoding ,Autopsy ,Drug Overdose ,Neuroscience ,Astrocyte ,Signal Transduction - Abstract
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.
- Published
- 2021