Journal Article

Research on the correlation of nitric oxide-induced neuronal cell pyroptosis with schizophrenia and its cognitive impairment

Teng, Zhaowei, Dai, Yu, Lei, Meijun, Yin, Rong, Tian, Yu, Liu, Fang, Wang, Xiaoqing, Yan, Ying

2025

Overview

Background Schizophrenia (SZ) is a severe mental illness that significantly impairs patients' quality of life and cognitive functioning. Objective This study investigates the role of nitric oxide (NO) in SZ pathogenesis by examining its induction of neuronal pyroptosis and its correlation with cognitive impairment. We aimed to identify potential therapeutic targets by analyzing the expression of pyroptosis-related genes (NLRP3, Caspase-1, GSDMD), inflammatory factors (IL-1β, IL-18), and SZ susceptibility genes (CUX2, DTNBP1). Methods (1) SH-SY5Y cells were treated with sodium nitroprusside (NO donor) at varying concentrations. Cell viability, NO levels, and gene expression were assessed using Cell Counting Kit-8(CCK-8), Griess reagent, and qPCR assays. (2) Clinical analysis included 58 SZ patients and 62 healthy controls. Cognitive function was evaluated using RBANS, and NO levels and gene expression were measured in blood samples. Results (1) NO treatment reduced SH-SY5Y cell viability and altered the expression of pyroptosis-related and susceptibility genes, and the IC 50 value of sodium nitroprusside on SH-SY5Y cells was 1.4 mM. (2) SZ patients exhibited elevated NO levels, reduced cognitive scores, and dysregulated gene expression compared to controls. NLRP3 and IL-18 were strongly associated with cognitive impairment. Conclusion NO serves an essential role in the pathological mechanisms of schizophrenia by inducing neuronal pyroptosis, potentially through the key factor NLRP3. Additionally, NLRP3 and IL-18 are strongly linked with cognitive impairment in schizophrenia.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Alzheimer's disease / Caspase-1 / Causes of / Cell culture / Cell death / Cell viability / Cholecystokinin / Cognition disorders / Cognitive ability / Cognitive impairment / Complications and side effects / Development and progression / Disease / Electroconvulsive therapy / Gene expression / Health aspects / Interleukin 18 / Medical research / Medicine / Medicine & Public Health / Mental disorders / Nervous system / Neuroblastoma / Neuropsychology / Nitric oxide / Pathogenesis / Patient Involvement in Psychiatric Research / Patients / Physiological aspects / Psychiatry / Psychotherapy / Pyroptosis / Quality of life / Schizophrenia / Sodium nitroprusside / Therapeutic targets