Dysregulation of Serum Exosomal Lipid Metabolism in Schizophrenia: A Biomarker Perspective.

Exosomes, crucial extracellular vesicles, have emerged as potential biomarkers for neurological conditions, including schizophrenia (SCZ). However, the exploration of exosomal lipids in the context of SCZ remains scarce, necessitating in-depth investigation. Leveraging ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), this study aimed to characterize the lipidomic profile of serum exosomes from SCZ patients, assessing their potential as novel biomarkers for SCZ diagnosis through absolute quantitative lipidomics. Our comprehensive lipidomic analysis unveiled 39 serum exosomal lipids that were differentially expressed between SCZ patients (n = 20) and healthy controls (HC, n = 20). These findings revealed a profound dysregulation in lipid metabolism pathways, notably in sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. Among these, seven exosomal lipids stood out for their diagnostic potential, exhibiting remarkable ability to differentiate SCZ patients from HCs with an unparalleled classification performance, evidenced by an area under the curve (AUC) of 0.94 (95% CI, 0.82-1.00). These lipids included specific ceramides and phosphoethanolamines, pointing to a distinct lipid metabolic fingerprint associated with SCZ. Furthermore, bioinformatic analyses reinforced the pivotal involvement of these lipids in SCZ-related lipid metabolic processes, suggesting their integral role in the disorder's pathophysiology. This study significantly advances our understanding of SCZ by pinpointing dysregulated exosomal lipid metabolism as a key factor in its pathology. The identified serum exosome-derived lipids emerge as compelling biomarkers for SCZ diagnosis, offering a promising avenue towards the development of objective and reliable diagnostic tools.

Paeoniflorin Rescued MK-801-Induced Schizophrenia-Like Behaviors in Mice via Oxidative Stress Pathway.

Schizophrenia (SCZ) affects approximately 1% population worldwide, and the first-line antipsychotics have partial reactivity or non-reactivity with side effects. Therefore, there is an urgent need to find more effective drugs. Paeoniflorin (PF) is the main effective component of traditional Chinese medicine from white peony, red peony and peony bark, which acts as a neuroprotective agent. The purpose of this study was to investigate whether PF can rescue MK-801 induced schizophrenia-like behavior in mice. Our results demonstrated that intragastric administration of PF ameliorated MK-801 induced schizophrenia-like behaviors in mice as demonstrated by prepulse inhibition of acoustic startle response, fear conditioning test for memory and open field test for activity. In contrast, the first-line antipsychotics-olanzapine reversed the prepulse inhibition deficits and hyperactivities, but not memory deficits, in the model mice. Further analysis showed that PF reduced oxidative stress in the MK-801-treated mice, as evidenced by the increased superoxide dismutase levels and decreased malondialdehyde levels in the blood of the model mice. In addition, PF treatment inhibited the expression of the apoptotic protein Bax and restored the expression of tyrosine hydroxylase in the brains of the model mice. in vitro data indicated that PF protected against oxidative stress induced neurotoxicity in the primary cultured hippocampal neurons. In conclusion, our results were the first to provide evidence that PF rescued schizophrenia-like behaviors (both positive symptoms and cognitive impairments) in rodents through oxidative stress pathway, and therefore provide a novel strategy for treatment of SCZ. However, more pre-clinical and clinical research are needed to translate the present findings into clinics for a treatment of schizophrenia.

Serum Exosome-Derived miR-139-5p as a Potential Biomarker for Major Depressive Disorder.

BACKGROUND: MicroRNAs (miRs) have been suggested to be biomarkers to inform the diagnosis of major depressive disorder (MDD). We have previously shown that exosome-derived miR-139-5p had potential in differentiating between patients with MDD and healthy control (HC) subjects. MATERIALS AND METHODS: To validate the potential of exosome-derived miR-139-5p as a biomarker for MDD, here we recruited 30 patients with MDD and 30 HC subjects, and used TaqMan probes to detect serum exosomal miR-139-5p levels. RESULTS: The data showed that patients with MDD had significantly increased exosomal miR-139-5p levels when compared with controls. Correlation analysis suggested that sex, age, and body mass index did not significantly affect blood exosomal miR-139-5p levels in the tested subjects. The ROC curve showed that serum-derived miR-139-5p had reasonable performance in discriminating patients with MDD and HC subjects, with a sensitivity of 0.867 and specificity of 0.767, and the AUC was 0.807. DISCUSSION: Taken together, these results demonstrated that patients with MDD were accompanied by significantly increased blood exosomal miR-139-5p levels, and exosomal miR-139-5p is a promising biomarker for the diagnosis of MDD.