Background and Hypothesis Schizophrenia (SCZ) is a multifaceted mental disorder marked by a spectrum of symptoms, including hallucinations, delusions, cognitive deficits, and negative symptoms. Its etiology involves intricate interactions between genetic and environmental factors, posing significant challenges for effective treatment. We hypothesized that intranasal administration of exosomes derived from nasal olfactory mucosal mesenchymal stem cells (OM-MSCs-exos) could alleviate SCZ-like behaviors in a murine model induced by methylazoxymethanol (MAM). Study Design We conducted a comprehensive investigation to assess the impact of intranasally delivered OM-MSC-exos on SCZ-like behaviors in MAM-induced mice. This study encompassed behavioral assessments, neuroinflammatory markers, glial activation, synaptic protein expression, and neurogenesis within the hippocampus. Study Results Our findings demonstrated that intranasal administration of OM-MSC-exos effectively ameliorated SCZ-like behaviors, specifically addressing social withdrawal and sensory gating deficits in the MAM-induced murine model. Furthermore, OM-MSC-exos intervention yielded a reduction in neuroinflammatory markers and a suppression of microglial activation within the hippocampus. Simultaneously, we observed an upregulation of key synaptic protein expression, including PSD95 and TH, the rate-limiting enzyme for dopamine biosynthesis. Conclusions Our study underscores the therapeutic potential of OM-MSC-exos in mitigating SCZ-like behavior. The OM-MSC-exos have the capacity to modulate glial cell activation, diminish neuroinflammation, and promote BDNF-associated synaptic plasticity and neurogenesis, thus ameliorating SCZ-like behaviors. In summary, intranasal administration of OM-MSC-exos offers a multifaceted approach to address SCZ mechanisms, promising innovative treatments for this intricate disorder.

中文翻译：

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释放鼻嗅粘膜间充质干细胞来源的外泌体的治疗潜力：恢复精神分裂症的突触可塑性、神经发生和神经炎症


背景和假设 精神分裂症 (SCZ) 是一种多方面的精神障碍，具有一系列症状，包括幻觉、妄想、认知缺陷和阴性症状。其病因涉及遗传和环境因素之间复杂的相互作用，对有效治疗提出了重大挑战。我们假设，鼻内施用源自鼻嗅粘膜间充质干细胞 (OM-MSCs-exos) 的外泌体可以减轻甲基偶氮甲醇 (MAM) 诱导的小鼠模型中的 SCZ 样行为。研究设计我们进行了一项全面的调查，以评估鼻内递送的 OM-MSC-exos 对 MAM 诱导的小鼠 SCZ 样行为的影响。这项研究包括行为评估、神经炎症标志物、神经胶质激活、突触蛋白表达和海马内的神经发生。研究结果我们的研究结果表明，鼻内施用 OM-MSC-exos 可以有效改善 SCZ 样行为，特别是解决 MAM 诱导的小鼠模型中的社交退缩和感觉门控缺陷。此外，OM-MSC-exos 干预减少了神经炎症标志物，并抑制了海马内的小胶质细胞活化。同时，我们观察到关键突触蛋白表达的上调，包括 PSD95 和 TH（多巴胺生物合成的限速酶）。结论 我们的研究强调了 OM-MSC-exos 在减轻 SCZ 样行为方面的治疗潜力。 OM-MSC-exos 能够调节神经胶质细胞活化、减少神经炎症、促进 BDNF 相关的突触可塑性和神经发生，从而改善 SCZ 样行为。 总之，鼻内施用 OM-MSC-exos 提供了一种解决 SCZ 机制的多方面方法，有望为这种复杂疾病提供创新治疗。