Integrative glycomic and proteomic analysis of mouse striatum and lateral hypothalamus following cocaine and methamphetamine treatment
Ontology highlight
ABSTRACT: Drug abuse is a major concern with few therapeutic options. Heparan sulfate (HS) and chondroitin sulfate (CS) interact with a plethora of growth factors and their receptors, and have profound effects on cellular signaling. Thus, targeting these dynamic interactions represents a novel therapeutic modality. Our previous studies have indicated increased HS proteoglycan syndecan-3 and identified HS as a resilience factor for cocaine abuse. Here, we utilized mass spectrometry-based glycomics and proteomics to understand the effects of cocaine (C) and methamphetamine (M) on HS, CS, and proteins from two brain regions: lateral hypothalamus (LH) and striatum (ST) from mice. We observed significant differences in HS and CS total abundances and percent sulfate contents and reduction in CS 4-O-sulfation, and increase in CS 6-O-sulfation for drug-treated (C and M) vs. saline samples. The proteomics data revealed a number of aberrant proteins in drug-treated vs. saline samples, including MYPR, KCC2A, SYN2, TENR, CALX, ANXA7, HDGF, NCAN, and CSPG5, and oxidative phosphorylation among the top perturbed pathway. Taken together, our study shows for the first time the novel relationship of HS, CS, and associated proteins with the drug abuse, and shed light on, the underlying neurobiological mechanism of drug dependence and novel therapeutic options.
INSTRUMENT(S): Q Exactive
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Brain
SUBMITTER: Manveen Sethi
LAB HEAD: Joseph Zaia
PROVIDER: PXD038576 | Pride | 2024-09-04
REPOSITORIES: Pride
ACCESS DATA