Direct reprogramming of hippocampal astrocytes ameliorates recognition memory in mice with cerebral ischemia

Abstract

Abstract The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger ribonucleic acid (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 × 1011 viral genomes) into post-stroke mice via the tail vein. mCherry/GFAP double-positive astrocyte-like glia were converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes in the hippocampus 56 days after cerebral ischemia. The new 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.