Modulating endogenous regenerative processes may represent a suitable treatment for central nervous system (CNS) injuries, such as stroke or trauma. Neural stem/progenitor cells (NS/PCs), which naturally reside in the subventricular zone (SVZ) of the adult brain, proliferate and differentiate to other cell types, and therefore may compensate the negative consequences of ischemic injury. The fate of NS/PCs in the developing brain is largely influenced by Wingless/Integrated (Wnt) signaling; however, its role in the differentiation of adult NS/PCs under ischemic conditions is still enigmatic. In our previous study, we identified the Wnt/β-catenin signaling pathway as a factor promoting neurogenesis at the expense of gliogenesis in neonatal mice. In this study, we used adult transgenic mice in order to assess the impact of the canonical Wnt pathway modulation (inhibition or hyper-activation) on NS/PCs derived from the SVZ, and combined it with the middle cerebral artery occlusion (MCAO) to disclose the effect of focal cerebral ischemia (FCI). Based on the electrophysiological properties of cultured cells, we first identified three cell types that represented in vitro differentiated NS/PCs - astrocytes, neuron-like cells, and precursor cells. Following FCI, we detected fewer neuron-like cells after Wnt signaling inhibition. Furthermore, the immunohistochemical analysis revealed an overall higher expression of cell-type-specific proteins after FCI, indicating increased proliferation and differentiation rates of NS/PCs in the SVZ. Remarkably, Wnt signaling hyper-activation increased the abundance of proliferating and neuron-like cells, while Wnt pathway inhibition had the opposite effect. Finally, the expression profiling at the single cell level revealed an increased proportion of neural stem cells and neuroblasts after FCI. These observations indicate that Wnt signaling enhances NS/PCs-based regeneration in the adult mouse brain following FCI, and supports neuronal differentiation in the SVZ.

• Klíčová slova
• Wnt signaling, adult neurogenesis, focal cerebral ischemia, gliogenesis, neural stem/progenitor cell, patch-clamp technique, single-cell RNA sequencing, transgenic mouse,
• Publikační typ
• časopisecké články MeSH

Wnt signaling plays an important role in the self-renewal, fate-commitment and survival of the neural stem/progenitor cells (NS/PCs) of the adult central nervous system (CNS). Ischemic stroke impairs the proper functioning of the CNS and, therefore, active Wnt signaling may prevent, ameliorate, or even reverse the negative effects of ischemic brain injury. In this review, we provide the current knowledge of Wnt signaling in the adult CNS, its status in diverse cell types, and the Wnt pathway's impact on the properties of NS/PCs and glial cells in the context of ischemic injury. Finally, we summarize promising strategies that might be considered for stroke therapy, and we outline possible future directions of the field.

• Klíčová slova
• Wnt signaling, adult neurogenesis, central nervous system, glia, ischemia, neural stem/progenitor cell, stroke, subgranular zone, subventricular zone,
• MeSH
• buněčná diferenciace genetika   MeSH
• cílená molekulární terapie metody   trendy   MeSH
• dospělí MeSH
• ischemie mozku genetika   metabolismus   patologie   patofyziologie   MeSH
• lidé MeSH
• mozek cytologie   patologie   fyziologie   MeSH
• nervové kmenové buňky patologie   fyziologie   MeSH
• neurogeneze fyziologie   MeSH
• neuroglie patologie   fyziologie   MeSH
• signální dráha Wnt genetika   fyziologie   MeSH
• tranzitorní ischemická ataka genetika   metabolismus   patologie   terapie   MeSH
• zdraví MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH