Lipidomic and Proteomic Insights from Extracellular Vesicles in Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes DOI Open Access
Chioma M. Okeoma, Wasifa Naushad, Bryson C. Okeoma

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 10, 2024

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation inflammatory pathways by substances may lead to glial chronic neuroinflammation, potentially mediated release extracellular particles (EPs), such as condensates (ECs) vesicles (EVs). These particles, which reflect physiological, pathophysiological, metabolic states their cells origin, might carry molecular signatures indicative SUD. In particular, our study investigated neuroinflammatory in SUD isolating EVs from dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) postmortem subjects. We isolated BA9-derived brain tissues eight individuals (controls: n=4, SUD: n=4). were analyzed for physical properties (concentration, size, zeta potential, morphology) subjected integrative multi-omics analysis profile lipidomic proteomic characteristics. assessed interactions bioactivity evaluating uptake cells. further effects on complement mRNA expression well microglial migration. No significant differences EV concentration, or surface markers observed between control groups. However, revealed enrichment glycerophosphoinositol bisphosphate (PIP2) EVs. Proteomic indicates downregulation SERPINB12, ACYP2, CAMK1D, DSC1, FLNB, upregulation C4A, C3, ALB Gene ontology protein-protein interactome analyses highlight functions cell motility, focal adhesion, acute phase response signaling that is associated with identified proteins. Both increased C3 C4 microglia, but only upregulated these genes astrocytes. also enhanced migration a wound healing assay.This successfully brains used approach identify EV-associated lipids proteins Elevated distinct suggest crucial role neuroinflammation.

Language: Английский

Lipidomic and Proteomic Insights from Extracellular Vesicles in Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes DOI Open Access
Chioma M. Okeoma, Wasifa Naushad, Bryson C. Okeoma

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 10, 2024

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation inflammatory pathways by substances may lead to glial chronic neuroinflammation, potentially mediated release extracellular particles (EPs), such as condensates (ECs) vesicles (EVs). These particles, which reflect physiological, pathophysiological, metabolic states their cells origin, might carry molecular signatures indicative SUD. In particular, our study investigated neuroinflammatory in SUD isolating EVs from dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) postmortem subjects. We isolated BA9-derived brain tissues eight individuals (controls: n=4, SUD: n=4). were analyzed for physical properties (concentration, size, zeta potential, morphology) subjected integrative multi-omics analysis profile lipidomic proteomic characteristics. assessed interactions bioactivity evaluating uptake cells. further effects on complement mRNA expression well microglial migration. No significant differences EV concentration, or surface markers observed between control groups. However, revealed enrichment glycerophosphoinositol bisphosphate (PIP2) EVs. Proteomic indicates downregulation SERPINB12, ACYP2, CAMK1D, DSC1, FLNB, upregulation C4A, C3, ALB Gene ontology protein-protein interactome analyses highlight functions cell motility, focal adhesion, acute phase response signaling that is associated with identified proteins. Both increased C3 C4 microglia, but only upregulated these genes astrocytes. also enhanced migration a wound healing assay.This successfully brains used approach identify EV-associated lipids proteins Elevated distinct suggest crucial role neuroinflammation.

Language: Английский

Citations

0