A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior

Odegaard, Katherine E.; Schaal, Victoria L.; Clark, Alexander R.; Koul, Sneh; Sankarasubramanian, Jagadesan; Xia, Zhiqiu; Mellon, Melissa; Uberti, Mariano; Liu, Yutong; Stothert, Andrew R.; Hook, Matthew J. Van; Wang, Hanjun; Guda, Chittibabu; Lisco, Steven J.; Pendyala, Gurudutt; Yelamanchili, Sowmya V.

doi:10.3389/fcell.2020.619199

Cited by 14 publications

(36 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, a mouse self-administration model of oxy showed that chronic oxy use altered the expression of several ephrin and semaphoring genes associated with axon guidance [32]. We have also previously shown alterations in axon guidance systems in our study of pre-and postnatal oxy exposure [7]. The differential regulation of these pathways may contribute to impaired neuronal structure and synaptic transmission in oxy-exposed individuals.…”

Section: Discussionmentioning

confidence: 51%

“…The cell pellet was lysed in RIPA buffer containing 1× protease and phosphatase cocktail inhibitor, followed by incubation on ice for 15 min. The samples were then sonicated three times at five-second intervals, followed by centrifugation at 10,000 RPM for 15 min at 4 • C. Protein quantification was carried out using Pierce BCA protein assay (Thermo Scientific, Rockford, IL, USA) as described in our earlier studies [6,7,[42][43][44][45][46]. A total of 50 µg of protein per sample per group was taken, and detergent was removed by chloroform/methanol extraction.…”

Section: Quantitative Proteomicsmentioning

confidence: 99%

“…Additionally, pre-and postnatal oxy exposure has been shown to have a generational impact on behavioral alterations and the expression of key genes associated with synaptic signaling [6]. Recently, our group has utilized electrophysiological studies to elucidate synaptic alterations associated with pre-and postnatal oxy exposure, identifying changes in excitatory postsynaptic signaling in the postnatal exposure group [7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Integrated Systems Analysis of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure

Guda

Odegaard

Tan

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Opioid abuse has become a major public health crisis that affects millions of individuals across the globe. This widespread abuse of prescription opioids and dramatic increase in the availability of illicit opioids have created what is known as the opioid epidemic. Pregnant women are a particularly vulnerable group since they are prescribed for opioids such as morphine, buprenorphine, and methadone, all of which have been shown to cross the placenta and potentially impact the developing fetus. Limited information exists regarding the effect of oxycodone (oxy) on synaptic alterations. To fill this knowledge gap, we employed an integrated system approach to identify proteomic signatures and pathways impacted on mixed neuroglial cultures treated with oxy for 24 h. Differentially expressed proteins were mapped onto global canonical pathways using ingenuity pathway analysis (IPA), identifying enriched pathways associated with ephrin signaling, semaphorin signaling, synaptic long-term depression, endocannabinoid signaling, and opioid signaling. Further analysis by ClueGO identified that the dominant category of differentially expressed protein functions was associated with GDP binding. Since opioid receptors are G-protein coupled receptors (GPCRs), these data indicate that oxy exposure perturbs key pathways associated with synaptic function.

show abstract

Section: Discussionmentioning

confidence: 51%

Section: Quantitative Proteomicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Integrated Systems Analysis of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure

Guda

Odegaard

Tan

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Using a pre- and post-natal oxy exposure rat model previously established in our lab, we employed a mass spectrometry-based proteomic approach to examine changes in the SV proteome from postnatal day 14 (P14) offspring from the in utero and post-natal oxy exposed offspring [ 11 , 17 , 18 ]. Subsequent pathway analysis of SV signatures highlighted several functional pathways affected by the differential expression of these SV signatures.…”

Section: Introductionmentioning

confidence: 99%

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

Odegaard

Gallegos

Koul

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Protein quantification was performed using Pierce BCA protein assay (Thermo Scientific, Rockford, IL, USA), as described in our earlier studies [51][52][53][54][55]. The mass spectrometry analysis was performed by a UNMC Mass Spectrometry Core (Omaha, NE, USA), and the protocol was based on the label-free quantitative mass spectrometry protocol described in our recently published studies [55][56][57].…”

Section: Mass Spectrometry Analysismentioning

confidence: 99%

Decoding the Synaptic Proteome with Long-Term Exposure to Midazolam during Early Development

Nguyen

Vellichirammal

Guda

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

The intensive use of anesthetic and sedative agents in the neonatal intensive care unit (NICU) has raised controversial concerns about the potential neurodevelopmental risks. This study focused on midazolam (MDZ), a common benzodiazepine regularly used as a sedative on neonates in the NICU. Mounting evidence suggests a single exposure to MDZ during the neonatal period leads to learning disturbances. However, a knowledge gap that remains is how long-term exposure to MDZ during very early stages of life impacts synaptic alterations. Using a preclinical rodent model system, we mimicked a dose-escalation regimen on postnatal day 3 (P3) pups until day 21. Next, purified synaptosomes from P21 control and MDZ animals were subjected to quantitative mass-spectrometry-based proteomics, to identify potential proteomic signatures. Further analysis by ClueGO identified enrichment of proteins associated with actin-binding and protein depolymerization process. One potential hit identified was alpha adducin (ADD1), belonging to the family of cytoskeleton proteins, which was upregulated in the MDZ group and whose expression was further validated by Western blot. In summary, this study sheds new information on the long-term exposure of MDZ during the early stages of development impacts synaptic function, which could subsequently perturb neurobehavioral outcomes at later stages of life.

show abstract

A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior

Cited by 14 publications

References 55 publications

Integrated Systems Analysis of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure

Integrated Systems Analysis of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure

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

Decoding the Synaptic Proteome with Long-Term Exposure to Midazolam during Early Development

Contact Info

Product

Resources

About