Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation
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,...
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MDPI AG
2022-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/4/510 |
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| author | Hilal A. Rather Shalini Mishra Yixin Su Ashish Kumar Sangeeta Singh Biswapriya B. Misra Jingyun Lee Cristina M. Furdui Lindsey R. Hamilton Robert W. Gould Susan H. Nader Michael A. Nader Gagan Deep |
| author_facet | Hilal A. Rather Shalini Mishra Yixin Su Ashish Kumar Sangeeta Singh Biswapriya B. Misra Jingyun Lee Cristina M. Furdui Lindsey R. Hamilton Robert W. Gould Susan H. Nader Michael A. Nader Gagan Deep |
| author_sort | Hilal A. Rather |
| collection | DOAJ |
| description | 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 (<i>n</i> = 11) and controls (<i>n</i> = 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 <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. |
| first_indexed | 2024-03-09T11:06:17Z |
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| id | doaj.art-8fc41901ac49420abc693edd1dea16fe |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T11:06:17Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8fc41901ac49420abc693edd1dea16fe2023-12-01T00:55:35ZengMDPI AGBiomolecules2218-273X2022-03-0112451010.3390/biom12040510Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout GestationHilal A. Rather0Shalini Mishra1Yixin Su2Ashish Kumar3Sangeeta Singh4Biswapriya B. Misra5Jingyun Lee6Cristina M. Furdui7Lindsey R. Hamilton8Robert W. Gould9Susan H. Nader10Michael A. Nader11Gagan Deep12Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USAIndependent Researcher, Pine-211, Raintree Park Dwaraka Krishna, Namburu 522508, Andhra Pradesh, IndiaWake Forest Baptist Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USAWake Forest Baptist Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USADepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USACocaine 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 (<i>n</i> = 11) and controls (<i>n</i> = 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 <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.https://www.mdpi.com/2218-273X/12/4/510cocaineextracellular vesiclescerebrospinal fluidbiomarkermass spectrometry |
| spellingShingle | Hilal A. Rather Shalini Mishra Yixin Su Ashish Kumar Sangeeta Singh Biswapriya B. Misra Jingyun Lee Cristina M. Furdui Lindsey R. Hamilton Robert W. Gould Susan H. Nader Michael A. Nader Gagan Deep Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation Biomolecules cocaine extracellular vesicles cerebrospinal fluid biomarker mass spectrometry |
| title | Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation |
| title_full | Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation |
| title_fullStr | Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation |
| title_full_unstemmed | Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation |
| title_short | Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation |
| title_sort | mass spectrometry based proteome profiling of extracellular vesicles derived from the cerebrospinal fluid of adult rhesus monkeys exposed to cocaine throughout gestation |
| topic | cocaine extracellular vesicles cerebrospinal fluid biomarker mass spectrometry |
| url | https://www.mdpi.com/2218-273X/12/4/510 |
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