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Open AccessArticle

Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration

1
Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
2
Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
3
Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA
4
Mass Spectrometry and Proteomics Core Facility, University of Nebraska Medical Center, Omaha, NE 68198, USA
*
Author to whom correspondence should be addressed.
Current address: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
Cells 2020, 9(8), 1883; https://doi.org/10.3390/cells9081883
Received: 20 June 2020 / Revised: 4 August 2020 / Accepted: 6 August 2020 / Published: 11 August 2020
(This article belongs to the Special Issue Sex Differences in Signaling Pathways)
Smoking remains a significant health and economic concern in the United States. Furthermore, the emerging pattern of nicotine intake between sexes further adds a layer of complexity. Nicotine is a potent psychostimulant with a high addiction liability that can significantly alter brain function. However, the neurobiological mechanisms underlying nicotine’s impact on brain function and behavior remain unclear. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation. To fill in this critical knowledge gap, our current study focused on identifying sex-specific brain-derived extracellular vesicles (BDEV) signatures in male and female rats post nicotine self-administration. Extracellular vesicles (EVs) are comprised of phospholipid nanovesicles such as apoptotic bodies, microvesicles (MVs), and exosomes based on their origin or size. EVs are garnering significant attention as molecules involved in cell–cell communication and thus regulating the pathophysiology of several diseases. Interestingly, females post nicotine self-administration, showed larger BDEV sizes, along with impaired EV biogenesis compared to males. Next, using quantitative mass spectrometry-based proteomics, we identified BDEV signatures, including distinct molecular pathways, impacted between males and females. In summary, this study has identified sex-specific changes in BDEV biogenesis, protein cargo signatures, and molecular pathways associated with long-term nicotine self-administration. View Full-Text
Keywords: nicotine; extracellular vesicles; sex differences; proteomics; bioinformatics nicotine; extracellular vesicles; sex differences; proteomics; bioinformatics
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    Description: ST1A&B - Normalized mass spectrometry files of total identified proteins for males and salines ST2A&B- Differentially expressed proteins identified in the males and females based on a criterion of 1.5 fold up/down and p<0.05
MDPI and ACS Style

Koul, S.; Schaal, V.L.; Chand, S.; Pittenger, S.T.; Nanoth Vellichirammal, N.; Kumar, V.; Guda, C.; Bevins, R.A.; Yelamanchili, S.V.; Pendyala, G. Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration. Cells 2020, 9, 1883. https://doi.org/10.3390/cells9081883

AMA Style

Koul S, Schaal VL, Chand S, Pittenger ST, Nanoth Vellichirammal N, Kumar V, Guda C, Bevins RA, Yelamanchili SV, Pendyala G. Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration. Cells. 2020; 9(8):1883. https://doi.org/10.3390/cells9081883

Chicago/Turabian Style

Koul, Sneh; Schaal, Victoria L.; Chand, Subhash; Pittenger, Steven T.; Nanoth Vellichirammal, Neetha; Kumar, Vikas; Guda, Chittibabu; Bevins, Rick A.; Yelamanchili, Sowmya V.; Pendyala, Gurudutt. 2020. "Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration" Cells 9, no. 8: 1883. https://doi.org/10.3390/cells9081883

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