Dataset Information

Brain cell-derived exosomes in plasma serve as neurodegeneration biomarkers in male cynomolgus monkeys self-administrating oxycodone.

ABSTRACT:

Background

The United States is currently facing an opioid crisis. Novel tools to better comprehend dynamic molecular changes in the brain associated with the opioid abuse are limited. Recent studies have suggested the usefulness of plasma exosomes in better understanding CNS disorders. However, no study has ever characterized exosomes (small extracellular vesicles of endocytic origin) secreted by brain cells to understand the potential neurodegenerative effects of long-term oxycodone self-administration (SA).

Methods

MRI of Cynomolgus monkeys (Macaca fascicularis) was performed to assess alterations in gray matter volumes with oxycodone SA. We isolated total exosomes (TE) from the plasma of these monkeys; from TE, we pulled-out neuron-derived exosomes (NDE), astrocytes-derived exosomes (ADE), and microglia-derived exosomes (MDE) using surface biomarkers L1CAM (L1 cell adhesion molecule), GLAST (Glutamate aspartate transporter) and TMEM119 (transmembrane protein119), respectively.

Findings

We observed a significantly lower gray matter volume of specific lobes of the brain (frontal and parietal lobes, and right putamen) in monkeys with ?3 years of oxycodone SA compared to controls. Higher expression of neurodegenerative biomarkers (NFL and ?-synuclein) correlates well with the change in brain lobe volumes in control and oxycodone SA monkeys. We also identified a strong effect of oxycodone SA on the loading of specific miRNAs and proteins associated with neuro-cognitive disorders. Finally, exosomes subpopulation from oxycodone SA group activated NF-?B activity in THP1- cells.

Interpretation

These results provide evidence for the utility of brain cells-derived exosomes from plasma in better understanding and predicting the pro-inflammatory and neurodegenerative consequence of oxycodone SA.

Funding

NIH.

SUBMITTER: Kumar A

PROVIDER: S-EPMC7804975 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brain cell-derived exosomes in plasma serve as neurodegeneration biomarkers in male cynomolgus monkeys self-administrating oxycodone.

Kumar Ashish A Kim Susy S Su Yixin Y Sharma Mitu M Kumar Pawan P Singh Sangeeta S Lee Jingyun J Furdui Cristina M CM Singh Ravi R Hsu Fang-Chi FC Kim Jeongchul J Whitlow Christopher T CT Nader Michael A MA Deep Gagan G

EBioMedicine 20210106

<h4>Background</h4>The United States is currently facing an opioid crisis. Novel tools to better comprehend dynamic molecular changes in the brain associated with the opioid abuse are limited. Recent studies have suggested the usefulness of plasma exosomes in better understanding CNS disorders. However, no study has ever characterized exosomes (small extracellular vesicles of endocytic origin) secreted by brain cells to understand the potential neurodegenerative effects of long-term oxycodone se ...[more]

PMID: 33418508

Similar Datasets

Project description:BACKGROUND: Non-human primates (NHP) are now being considered as models for investigating human metabolic diseases including diabetes. Analyses of cholesterol and triglycerides in plasma derived from NHPs can easily be achieved using methods employed in humans. Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the plasma lipidome from 16 cynomolgus monkey, Macaca fascicularis, using liquid chromatography coupled with mass spectrometry (LC/MS). We established novel analytical approaches, which are based on a simple gradient elution, to quantify polar lipids in plasma including (i) glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA); (ii) sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucocyl-ceramide, GluCer; ganglioside mannoside 3, GM3). Lipidomic analysis had revealed that the plasma of human and cynomolgus monkey were of similar compositions, with PC, SM, PE, LPC and PI constituting the major polar lipid species present. Human plasma contained significantly higher levels of plasmalogen PE species (p<0.005) and plasmalogen PC species (p<0.0005), while cynomolgus monkey had higher levels of polyunsaturated fatty acyls (PUFA) in PC, PE, PS and PI. Notably, cynomolgus monkey had significantly lower levels of glycosphingolipids, including GluCer (p<0.0005) and GM(3) (p<0.0005), but higher level of Cer (p<0.0005) in plasma than human. We next investigated the biochemical alterations in blood lipids of 8 naturally occurring diabetic cynomolgus monkeys when compared with 8 healthy controls. CONCLUSIONS: For the first time, we demonstrated that the plasma of human and cynomolgus monkey were of similar compositions, but contained different mol distribution of individual molecular species. Diabetic monkeys exhibited decreased levels of sphingolipids, which are microdomain-associated lipids and are thought to be associated with insulin sensitivity. Significant increases in PG species, which are precursors for cardiolipin biosynthesis in mitochondria, were found in fasted diabetic monkeys (n?=?8).

Dataset Information

Brain cell-derived exosomes in plasma serve as neurodegeneration biomarkers in male cynomolgus monkeys self-administrating oxycodone.

Background

Methods

Findings

Interpretation

Funding

Publications

Brain cell-derived exosomes in plasma serve as neurodegeneration biomarkers in male cynomolgus monkeys self-administrating oxycodone.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets