Dataset Information

Investigating the Succinylome and Malonylome of Schizophrenia

ABSTRACT: The succinylome and malonylome of human oligodendrocyte precursors (MO3.13 line) and postmortem brain tissue (whole lysates and mitochondrial enrichments) were studied with shotgun mass spectrometry. The goal was to determine what changes in oligodendrocytes are induced with the addition of the NMDA receptor antagonist MK-801 and compare this with schizophrenia brain tissue; to visualize the changes that antipsychotics have on the succinylome and malonylome and how this may relate to their side effects; to see what changes induced by MK-801 are returned to more control-like levels and how this may relate to mechanisms of drug action; and to see what changes in these PTMs may exist in vivo in patients with schizophrenia compared to healthy controls.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Oligodendrocyte Precursor Cell, Cell Culture

DISEASE(S): Schizophrenia

SUBMITTER: Bradley Smith

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD014188 | Pride | 2022-10-13

REPOSITORIES: Pride

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Publications

Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia.

Smith Bradley Joseph BJ Brandão-Teles Caroline C Zuccoli Giuliana S GS Reis-de-Oliveira Guilherme G Fioramonte Mariana M Saia-Cereda Verônica M VM Martins-de-Souza Daniel D

Journal of personalized medicine 20220830 9

Two protein post-translational modifications, lysine succinylation and malonylation, are implicated in protein regulation, glycolysis, and energy metabolism. The precursors of these modifications, succinyl-CoA and malonyl-CoA, are key players in central metabolic processes. Both modification profiles have been proven to be responsive to metabolic stimuli, such as hypoxia. As mitochondrial dysfunction and metabolic dysregulation are implicated in schizophrenia and other psychiatric illnesses, the ...[more]

PMID: 36143193

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Project description:N-Methyl-D-aspartate receptors (NMDAr), widely located around the central nervous system, are known to be involved in behavioral disorders. Dizocilpine (commonly referred to as MK-801) is a well known non-competitive NMDAr antagonist. We treated rats with intraperitoneal injection [0.08 (low-dose) and 0.16 (high-dose) mg/kg] of MK-801. In one experiment, 40 min after NaCl (vehicle control) and MK-801 (0.08 mg/kg) injection, electrocorticogram (ECoG) signals were analyzed. In the second experiment, 40 min post-injection, the whole brain of each animal was rapidly removed and separated into amyglada, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum) on ice, followed by analysis using a 4x44K DNA microarray chip. Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline (30-80 Hz) frequency oscillations. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose of MK-801. Under high-dose, ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. MK-801 increases the synchrony of baseline oscillations, causing very early changes in gene expressions in rat brain after acute MK-801 treatment, a first report. The overall goal of the present study was to identify gene expression patterns along rat chromosomes in different brain regions after a single injection of MK-801, which exerts a longer acute effect than ketamine on ongoing brain activities. Two approaches were taken, first electrophysiological and send molecular analysis, where the brain of MK-801-treated rats was subjected to a genome-wide transcriptome mapping analysis (~4400 genes) in the cerebral cortex, midbrain, hippocampus, ventral striatum, amygdala, and hypothalamus regions.

Dataset Information

Investigating the Succinylome and Malonylome of Schizophrenia

Publications

Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia.

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