Unlocking the Therapeutic Potential of Exosomes Derived From Nasal Olfactory Mucosal Mesenchymal Stem Cells: Restoring Synaptic Plasticity, Neurogenesis, and Neuroinflammation in Schizophrenia

Abstract 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.