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Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia.
- Source :
-
Scientific reports [Sci Rep] 2024 Sep 03; Vol. 14 (1), pp. 20521. Date of Electronic Publication: 2024 Sep 03. - Publication Year :
- 2024
-
Abstract
- 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 <superscript>11</superscript> 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Male
Neurons metabolism
Memory
Mice, Inbred C57BL
Genetic Vectors genetics
Genetic Vectors administration & dosage
Polypyrimidine Tract-Binding Protein metabolism
Polypyrimidine Tract-Binding Protein genetics
Astrocytes metabolism
Hippocampus metabolism
Hippocampus pathology
Brain Ischemia metabolism
Brain Ischemia therapy
Neurogenesis
Heterogeneous-Nuclear Ribonucleoproteins metabolism
Heterogeneous-Nuclear Ribonucleoproteins genetics
Disease Models, Animal
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 39227632
- Full Text :
- https://doi.org/10.1038/s41598-024-71212-w