Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia

Yusuke Fukui; Ryuta Morihara; Xinran Hu; Yumiko Nakano; Taijun Yunoki; Mami Takemoto; Toru Yamashita

doi:10.1038/s41598-024-71212-w

journal article Open Access Sep 03, 2024

Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia

Yusuke Fukui Ryuta Morihara

Xinran Hu Yumiko Nakano Taijun Yunoki Mami Takemoto Toru Yamashita

Scientific Reports Vol. 14 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41598-024-71212-w

Abstract

AbstractThe 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 × 1011 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.

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References

Details

Published: Sep 03, 2024
Vol/Issue: 14(1)
License: View

Authors

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

Department of Neurology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

T

Toru Yamashita

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

Funding

Japan Society for the Promotion of Science Award: JP22K17799

the Research Committees (Toba K, and Tsuji S) from the Japan Agency for Medical Research and Development

Cite This Article

Yusuke Fukui, Ryuta Morihara, Xinran Hu, et al. (2024). Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-024-71212-w

Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia

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