Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure

Authors

Katherine E. Odegaard, University of Nebraska Medical Center
Gabriel Gallegos, University of Nebraska Medical Center
Sneh Koul, University of Nebraska Medical Center
Victoria L. Schaal, University of Nebraska Medical CenterFollow
Neetha N. Vellichirammal, University of Nebraska Medical Center
Chittibabu Guda, University of Nebraska Medical CenterFollow
Andrea P. Dutoit, University of Nebraska Medical CenterFollow
Steven J. Lisco, University of Nebraska Medical CenterFollow
Sowmya V. Yelamanchili, University of Nebraska Medical CenterFollow
Gurudutt Pendyala, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Cells

Publication Date

2022

Volume

11

Abstract

The current opioid crisis, which has ravaged all segments of society, continues to pose a rising public health concern. Importantly, dependency on prescription opioids such as oxycodone (oxy) during and after pregnancy can significantly impact the overall brain development of the exposed offspring, especially at the synapse. A significant knowledge gap that remains is identifying distinct synaptic signatures associated with these exposed offspring. Accordingly, the overall goal of this current study was to identify distinct synaptic vesicle (SV) proteins as signatures for offspring exposed to oxy in utero (IUO) and postnatally (PNO). Using a preclinical animal model that imitates oxycodone exposure in utero (IUO) and postnatally (PNO), we used a quantitative mass spectrometry-based proteomics platform to examine changes in the synaptic vesicle proteome on post-natal day 14 (P14) IUO and PNO offspring. We identified MEGF8, associated with carpenter syndrome, to be downregulated in the IUO offspring while LAMTOR4, associated with the regulator complex involved in lysosomal signaling and trafficking, was found to be upregulated in the PNO groups, respectively. Their respective differential expression was further validated by Western blot. In summary, our current study shows exposure to oxy in utero and postnatally can impact the SV proteome in the exposed offspring and the identification of these distinct SV signatures could further pave the way to further elucidate their downstream mechanisms including developing them as potential therapeutic targets.

MeSH Headings

Animals, Female, Guanine Nucleotide Exchange Factors, Humans, Membrane Proteins, Oxycodone, Pregnancy, Prenatal Exposure Delayed Effects, Proteome, Proteomics, Synapses, Synaptic Vesicles

DOI Link

10.3390/cells11111740

ISSN

2073-4409

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Odegaard, Katherine E.; Gallegos, Gabriel; Koul, Sneh; Schaal, Victoria L.; Vellichirammal, Neetha N.; Guda, Chittibabu; Dutoit, Andrea P.; Lisco, Steven J.; Yelamanchili, Sowmya V.; and Pendyala, Gurudutt, "Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure" (2022). Journal Articles: Anesthesiology. 20.
https://digitalcommons.unmc.edu/com_anesth_articles/20