Intranasal wnt-3a alleviates neuronal apoptosis in early brain injury post subarachnoid hemorrhage via the regulation of wnt target PPAN mediated by the moonlighting role of aldolase C

Publication date: Available online 31 December 2019Source: Neurochemistry InternationalAuthor(s): Wu Ruan, Junwen Hu, Hang Zhou, Yin Li, Chaoran Xu, Yujie Luo, Ting Chen, Bangliang Xu, Feng Yan, Gao ChenAbstractNeuronal apoptosis is one of the main pathophysiological events in the early brain injury (EBI) post subarachnoid hemorrhage (SAH). Wnt-3a, one of the endogenous wnt ligands crucial in neurogenesis, has been proven to be efficacious in neuroprotection in traumatic brain injury and ischemic stroke. The glycolytic enzyme aldolase C and ribosome biogenesis protein PPAN were revealed to be linked to wnt signaling pathway. The aim of the study was to explore the antiapoptotic effects of intranasal wnt-3a through Frizzled-1 (Frz-1)/aldolase C/PPAN pathway in SAH. Approaches for assessment included SAH grade, Garcia test, brain water content evaluation, rotarod test, Morris water maze test, Western blot, immunofluorescence and transmission electron microscopy. The results showed that wnt-3a improved the neurological scores, brain water content and long-term neurobehavioral functions after SAH. Wnt-3a increased the level of Frz-1, aldolase C, β-catenin, PPAN and the Bcl-2/Bax ratio; and decreased the level of axin and cleaved caspase-3 (CC-3). The anti-apoptotic effect of wnt-3a was further evidenced by TUNEL staining and subcellular structure imaging. Frz-1 siRNA and aldolase C siRNA offset the effects of wnt-3a; and restoration of aldolase C by aldolase C CRISPR in Frz-...
Source: Neurochemistry International - Category: Neuroscience Source Type: research

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