Influence of syringic acid on schizophrenia in mice: Modulation of PI3K/AKT1/GSK3β signaling pathway, galectin-3 and MBP.

Abstract

Schizophrenia is a highly debilitating mental disorder characterized by a variety of neurodevelopmental and behavioral issues. There is mounting evidence that neuroinflammation and myelin deficiency are the coexisting pathological features that lead to schizophrenia. Thus, the current work investigated the therapeutic potential of syringic acid (SA) in ameliorating neuroinflammation and demyelination in a mouse model of cuprizone (CPZ)-induced schizophrenia. Schizophrenia in mice was induced by 0.2% CPZ in diet for 6 weeks. Male Swiss mice were randomly divided into four groups: 1st group: Normal control group received normal chow for 6 weeks, 2nd group: CPZ, 3rd Group: Mice received CPZ + SA (50 mg/kg; orally). 4th group: Mice received CPZ + SA (100 mg/kg; orally). Our results showed that CPZ induced behavioral, biochemical, molecular and histopathological changes, while SA significantly alleviated behavioral abnormalities induced by CPZ. Furthermore, SA increased Pi form of glutathione-S-transferase (GST-π), myelin basic protein (MBP), neuregulin-1 (NRG-1), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3k), and protein kinase B (Akt1). Additionally, it lessened glial fibrillary acidic protein (GFAP), galectin-3, glycogen synthase kinase 3 beta (GSK-3β), and tumor necrosis factor-α (TNF-α). Moreover, SA relieved histopathological alterations in the brain induced by CPZ. The above findings suggest that SA could ameliorate CPZ-induced psychotic symptoms in mice via suppressing neuroinflammation and promoting myelin integrity, perhaps providing further benefits to people suffering from schizophrenia.