Schizophrenia bulletin · 2026
Robo2-Nrxn3 Deficiency: A Molecular Hub Linking Excitation-Inhibition Imbalance to the Pathogenesis of Schizophrenia.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liu Senqi, Zhang Yujuan, Liu Kang, Guo Xiaoge, Li Jinming, Li Ranran, Yang Yongfeng, Zhao Jingyuan, Zhang Jianhong, Wang Xiujuan, Ding Shuang, Luo Binbin, Han Yong, Zhang Luwen, Lv Luxian, Su Xi
Аннотация
BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is characterized by excitation-inhibition (E-I) imbalance as a core pathophysiological feature, but its molecular underpinnings remain elusive. Susceptibility gene Roundabout2 (Robo2), which regulates E-I balance in the central nervous system, may play a critical role in the pathogenesis of SZ by contributing to this dysregulation.
STUDY DESIGN: We conducted a transcriptomic analysis of Robo2 in postmortem brain tissues from patients with SZ and controls using the GEO/GSE datasets. The plasma levels of Robo2 were quantified in clinical cohorts via ELISA. We assessed the correlation between plasma Robo2 levels and clinical assessments (Positive and Negative Syndrome Scale [PANSS] and MATRICS Consensus Cognitive Battery [MCCB]) or neurophysiological measures (functional near-infrared spectroscopy [fNIRS] and event-related potentials). Rats with hippocampal Robo2 knockdown underwent comprehensive behavioral, electrophysiological, and ultrastructural (Golgi staining) assessments. Proteomic sequencing with pathway enrichment analysis was conducted to identify downstream molecular mediators.
STUDY RESULTS: Hippocampal and plasma Robo2 expression were significantly downregulated in patients with SZ. The plasma levels of Robo2 were inversely correlated with PANSS scores and positively associated with MCCB performance. Neurophysiological correlations revealed positive associations between Robo2 and dorsolateral prefrontal cortex activation (fNIRS and P300 peak amplitude). Robo2-deficient rats exhibited anxiety-like behaviors, cognitive impairments, social withdrawal, and sensory gating abnormalities, accompanied by decreased dendritic spine density and increased hippocampal field potential power. Proteomics identified disrupted GABAergic/glutamatergic synaptic pathways, with neurexin-3 (Nrxn3) downregulation emerging as a potential downstream candidate.
CONCLUSIONS: Our findings established Robo2-Nrxn3 deficiency as a potential molecular hub linking E-I imbalance to SZ-associated behavioral and neurophysiological deficits, highlighting novel therapeutic targets for E-I modulation.
STUDY DESIGN: We conducted a transcriptomic analysis of Robo2 in postmortem brain tissues from patients with SZ and controls using the GEO/GSE datasets. The plasma levels of Robo2 were quantified in clinical cohorts via ELISA. We assessed the correlation between plasma Robo2 levels and clinical assessments (Positive and Negative Syndrome Scale [PANSS] and MATRICS Consensus Cognitive Battery [MCCB]) or neurophysiological measures (functional near-infrared spectroscopy [fNIRS] and event-related potentials). Rats with hippocampal Robo2 knockdown underwent comprehensive behavioral, electrophysiological, and ultrastructural (Golgi staining) assessments. Proteomic sequencing with pathway enrichment analysis was conducted to identify downstream molecular mediators.
STUDY RESULTS: Hippocampal and plasma Robo2 expression were significantly downregulated in patients with SZ. The plasma levels of Robo2 were inversely correlated with PANSS scores and positively associated with MCCB performance. Neurophysiological correlations revealed positive associations between Robo2 and dorsolateral prefrontal cortex activation (fNIRS and P300 peak amplitude). Robo2-deficient rats exhibited anxiety-like behaviors, cognitive impairments, social withdrawal, and sensory gating abnormalities, accompanied by decreased dendritic spine density and increased hippocampal field potential power. Proteomics identified disrupted GABAergic/glutamatergic synaptic pathways, with neurexin-3 (Nrxn3) downregulation emerging as a potential downstream candidate.
CONCLUSIONS: Our findings established Robo2-Nrxn3 deficiency as a potential molecular hub linking E-I imbalance to SZ-associated behavioral and neurophysiological deficits, highlighting novel therapeutic targets for E-I modulation.