Despite the experimental evidence pointing to a significant role of the Wnt family of proteins in physiological and pathological rodent spinal cord functioning, its potential relevance in the healthy and traumatically injured human spinal cord as well as its therapeutic potential in spinal cord injury (SCI) are still poorly understood. To get further insight into these interesting issues, we first demonstrated by quantitative Real-Time PCR and simple immunohistochemistry that detectable mRNA expression of most Wnt components, as well as protein expression of all known Wnt receptors, can be found in the healthy human spinal cord, supporting its potential involvement in human spinal cord physiology. Moreover, evaluation of Frizzled (Fz) 1 expression by double immunohistochemistry showed that its spatio-temporal and cellular expression pattern in the traumatically injured human spinal cord is equivalent to that observed in a clinically relevant model of rat SCI and suggests its potential involvement in SCI progression/outcome. Accordingly, we found that long-term lentiviral-mediated overexpression of the Fz1 ligand Wnt1 after rat SCI improves motor functional recovery, increases myelin preservation and neuronal survival, and reduces early astroglial reactivity and NG2+ cell accumulation, highlighting the therapeutic potential of Wnt1 in this neuropathological situation.

中文翻译：

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Frizzled 1 和 Wnt1 作为创伤性脊髓损伤的新潜在治疗靶点。


尽管实验证据表明 Wnt 蛋白家族在生理和病理性啮齿动物脊髓功能中发挥着重要作用，但其与健康和创伤性损伤的人类脊髓的潜在相关性以及其在脊髓损伤 (SCI) 中的治疗潜力尚不清楚。仍然知之甚少。为了进一步深入了解这些有趣的问题，我们首先通过定量实时 PCR 和简单的免疫组织化学证明，在健康的人脊髓中可以发现大多数 Wnt 成分的可检测 mRNA 表达以及所有已知 Wnt 受体的蛋白质表达，支持其可能参与人类脊髓生理学。此外，通过双重免疫组织化学对 Frizzled (Fz) 1 表达的评估表明，其在创伤性损伤的人脊髓中的时空和细胞表达模式与在临床相关的大鼠 SCI 模型中观察到的相同，并表明其可能参与 SCI进展/结果。因此，我们发现大鼠 SCI 后长期慢病毒介导的 Fz1 配体 Wnt1 过度表达可改善运动功能恢复，增加髓磷脂保存和神经元存活，并减少早期星形胶质细胞反应性和 NG2+ 细胞积累，突出了 Wnt1 在这方面的治疗潜力。神经病理情况。