Background and Hypothesis This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. Study Design This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. Study Results Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. Conclusions Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.

中文翻译：

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揭示前额皮质-基底外侧杏仁核通路对精神分裂症认知障碍的作用：患者和小鼠模型的多模式研究


背景和假设本研究使用各种技术研究了内侧前额皮质（mPFC）-基底外侧杏仁核（BLA）通路在精神分裂症（SCZ）相关认知障碍中的作用。研究设计本研究利用临床量表、磁共振成像、单细胞 RNA 测序和光遗传学来研究 SCZ 患者的 mPFC-BLA 通路。在小鼠模型中，6 周大的醋酸甲基偶氮甲醇诱导的小鼠表现出明显的认知缺陷，通过立体定位注射腺相关病毒载体来揭示 mPFC 和 BLA 之间的神经联系来解决这一问题。研究结果发现 SCZ 患者和健康对照组之间的脑容量和神经活动存在显着差异，特别是在背外侧前额叶皮层 (DLPFC) 和 BLA 区域。此外，我们观察到相关性表明 DLPFC 和 BLA 体积的减少与较低的认知功能得分相关。 mPFC-BLA 通路的激活显着改善了 SCZ 模型小鼠的认知表现，但单独针对兴奋性或抑制性神经元无法复制这种效果。单细胞转录组分析揭示了 SCZ 模型小鼠 BLA 兴奋性和抑制性神经元的基因表达差异。值得注意的是，在 SCZ 患者的血液外泌体中也发现了这些模型小鼠 BLA 中差异表达的基因。结论 我们的研究全面了解了 PFC-BLA 通路在 SCZ 中的作用，强调了其在认知障碍中的重要性，并提供了新的诊断和治疗途径。 此外，我们的研究强调了血液外泌体 mRNA 作为 SCZ 诊断无创生物标志物的潜力，强调了该方法的临床可行性和实用性。