{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:21:01Z","timestamp":1783441261936,"version":"3.54.6"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Research on Substance Use and Addiction, Wake Forest School of Medicine and NIH","award":["R01 DA049267 and R01 DA025120"],"award-info":[{"award-number":["R01 DA049267 and R01 DA025120"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cocaine use disorder has been reported to cause transgenerational effects. However, due to the lack of standardized biomarkers, the effects of cocaine use during pregnancy on postnatal development and long-term neurobiological and behavioral outcomes have not been investigated thoroughly. Therefore, in this study, we examined extracellular vesicles (EVs) in adult (~12 years old) female and male rhesus monkeys prenatally exposed to cocaine (n = 11) and controls (n = 9). EVs were isolated from the cerebrospinal fluid (CSF) and characterized for the surface expression of specific tetraspanins, concentration (particles\/mL), size distribution, and cargo proteins by mass spectrometry (MS). Transmission electron microscopy following immunogold labeling for tetraspanins (CD63, CD9, and CD81) confirmed the successful isolation of EVs. Nanoparticle tracking analyses showed that the majority of the particles were &lt;200 nm in size, suggesting an enrichment for small EVs (sEV). Interestingly, the prenatally cocaine-exposed group showed ~54% less EV concentration in CSF compared to the control group. For each group, MS analyses identified a number of proteins loaded in CSF-EVs, many of which are commonly listed in the ExoCarta database. Ingenuity pathway analysis (IPA) demonstrated the association of cargo EV proteins with canonical pathways, diseases and disorders, upstream regulators, and top enriched network. Lastly, significantly altered proteins between groups were similarly characterized by IPA, suggesting that prenatal cocaine exposure could be potentially associated with long-term neuroinflammation and risk for neurodegenerative diseases. Overall, these results indicate that CSF-EVs could potentially serve as biomarkers to assess the transgenerational adverse effects due to prenatal cocaine exposure.<\/jats:p>","DOI":"10.3390\/biom12040510","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:40:14Z","timestamp":1648590014000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-917X","authenticated-orcid":false,"given":"Hilal A.","family":"Rather","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2589-6539","authenticated-orcid":false,"given":"Biswapriya B.","family":"Misra","sequence":"additional","affiliation":[{"name":"Independent Researcher, Pine-211, Raintree Park Dwaraka Krishna, Namburu 522508, Andhra Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina M.","family":"Furdui","sequence":"additional","affiliation":[{"name":"Wake Forest Baptist Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"},{"name":"Department of Internal Medicine, Section on Molecular Medicine; Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey R.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-1874","authenticated-orcid":false,"given":"Robert W.","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"},{"name":"Center for Addiction Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan H.","family":"Nader","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Nader","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"},{"name":"Center for Addiction Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4445-8796","authenticated-orcid":false,"given":"Gagan","family":"Deep","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"},{"name":"Wake Forest Baptist Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"},{"name":"Center for Addiction Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ref_1","unstructured":"Substance Abuse and Mental Health Services Administration (2020). 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