| Field |
Value |
| Identifier |
nemo:dat-zngw2c8 |
| Dataset Name |
Transcriptional impacts of substance use disorder and HIV on human ventral midbrain neurons and microglia |
| Version |
NA |
| Release Date |
NA |
| DOI |
NA |
| Source Data URL |
NA |
| Dataset Collection URL |
NA |
| Description |
For people with HIV, substance use disorders (SUDs) are a prominent neurological risk factor, and impacts of both on dopaminergic pathways are a potential point of deleterious convergence. Insight about cellular changes related to HIV and/or SUD is limited, but would be valuable for informing interventions. We explore cell-type-specific transcriptional alterations in chronic HIV and opioid/cocaine SUD in postmortem substantia nigra, performing single-nucleus RNA sequencing for 90 donors. Using abnormality-tolerant analysis, we identify changes in dopaminergic/GABAergic neurons and microglia, and functional gene groups with highly coordinated altered expression across donors. We find that HIV but not SUD is associated with reduced dopamine transporter transcription in dopaminergic neurons, whereas SUD involves increased excitability, impaired postsynaptic function, and reduced-frequency presynaptic release. We observe HIV/SUD synergies that emerge only with both conditions present. For controlled HIV, synergies may permit HIV viral replication and mediate cytotoxic dopaminergic neuron damage. In uncontrolled HIV, synergies include SUD-mediated impacts on GABAergic/dopaminergic neurons that promote dopaminergic disinhibition. |
| Keywords |
Substantia nigra; postmortem; HIV; substance use disorder; opioids; cocaine; single-nucleus RNA sequencing; SCORCH |
| Total Files in Collection |
0 |
| Total Size in Collection (in GB) |
0.0 |
| Authors |
Alyssa M. Wilson, Michelle M. Jacobs, Tova Y. Lambert, Aditi Valada, Gregory Meloni, Evan Gilmore, Jacinta Murray, Schahram Akbarian, Susan Morgello |
| Organization |
Icahn School of Medicine at Mount Sinai |
| Contact Person |
Alyssa M. Wilson |
| Contact E-Mail |
alyssa.wilson@mssm.edu |
| External Identifier |
NA |
| Grant Name |
National Institutes of Health grant U01DA053600 (SA, SM), National Institutes of Health grant R61DA048207 (SA, SM), National Institutes of Health grant R01NS108801 (SM), National Institutes of Health grant RFAG060961 (SM), National Institutes of Health grant U24MH100931 (SM), National Institutes of Health contract 75N95023C00015 (SM), National Institutes of Health Office of Research Infrastructure grant S10OD026880 (Patricia Kovach, ISMMS), National Institutes of Health Office of Research Infrastructure grant S10OD030463 (Patricia Kovach, ISMMS)
National Center for Advancing Translational Sciences Clinical and Translational Science Awards grant UL1TR004419 (Rosalind Wright, ISMMS) |
| Consortium |
SCORCH |
| Data Repository |
NeMO and dbGaP |
| Data Repository RRID |
RRID:SCR_016152 |
| Data License |
Public data available under CC BY 4.0 |
| Data Access |
This data is controlled-access. The following data use limitations apply to this data and are based on the original informed consent from the participant. First, use of the data is limited to health/medical/biomedical purposes and does not include the study of population origins or ancestry. Second, the data requestor must provide documentation of local IRB approval. Third, the requestor agrees to make results of studies using the data available to the larger scientific community. |
| Community Standards |
NA |
| Study Organism |
Human |
| Protocol ID |
NA |
