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

Area of Science:

• Neuroscience
• Developmental Biology
• Pharmacology

Background:

• The ongoing opioid crisis presents a significant public health challenge.
• Prenatal and postnatal exposure to prescription opioids like oxycodone can adversely affect offspring brain development, particularly synaptic function.
• There is a critical need to identify specific synaptic markers associated with such exposures.

Purpose of the Study:

• To identify distinct synaptic vesicle (SV) protein signatures in offspring exposed to oxycodone in utero (IUO) and postnatally (PNO).
• To investigate the impact of maternal and early-life oxycodone exposure on the synaptic vesicle proteome.

Main Methods:

• Utilized a preclinical animal model mimicking in utero and postnatal oxycodone exposure.
• Employed quantitative mass spectrometry-based proteomics to analyze synaptic vesicle proteomes in offspring at post-natal day 14.
• Validated differential protein expression using Western blot analysis.

Main Results:

• Identified downregulation of MEGF8 (associated with Carpenter syndrome) in IUO offspring.
• Observed upregulation of LAMTOR4 (involved in lysosomal signaling) in PNO offspring.
• Confirmed distinct changes in the synaptic vesicle proteome due to oxycodone exposure.

Conclusions:

• Oxycodone exposure in utero and postnatally alters the synaptic vesicle proteome in offspring.
• The identified synaptic vesicle protein signatures may help elucidate downstream mechanisms.
• These signatures could serve as potential therapeutic targets for mitigating opioid exposure effects.