Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama, 700-8558, Japan.
Sci Rep. 2024 Sep 3;14(1):20521. doi: 10.1038/s41598-024-71212-w.
The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 × 10 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia.
抑制脑卒中后痴呆小鼠模型中多嘧啶 tract 结合蛋白 1（Ptbp1）信使 RNA 的治疗潜力尚未通过病毒转导进行检验。在这项研究中，在脑缺血后 3 天，我们通过尾静脉向脑卒中后的小鼠注射含有腺相关病毒（AAV）-pGFAP-mCherry 和 AAV-pGFAP-CasRx（对照载体）或 AAV-pGFAP-mCherry 和 AAV-pGFAP-CasRx-SgRNA-（Ptbp1）（1:5，1.0×10 病毒基因组）的病毒载体混合物。在脑缺血后 56 天，我们观察到在海马体中出现了新的 mCherry/NeuN 双阳性神经元样细胞。一部分 mCherry/GFAP 双阳性星形胶质细胞样胶质细胞可能已经转化为具有形态变化的新的 mCherry/NeuN 双阳性神经元样细胞。新的神经元细胞整合到齿状回中，识别记忆得到显著改善。这些结果表明，通过抑制 Ptbp1 将海马体星形胶质细胞样胶质细胞体内转化为功能性新神经元可能是治疗脑卒中后痴呆的一种策略。
