Publication

Conversion of Reactive Astrocytes to Induced Neurons Enhances Neuronal Repair and Functional Recovery After Ischemic Stroke

Persistent URL
Last modified
  • 05/14/2025
Type of Material
Authors
    Mchael Qize Jiang, Emory UniversityShan Ping Yu, Emory UniversityZheng Zachory Wei, Emory UniversityWeiwei Zhong, Emory UniversityWenyuan Cao, Emory UniversityXiaohuan Gu, Emory UniversityAnika Wu, Emory UniversityMyles Randolph McCrary, Emory UniversityKen Berglund, Atlanta Veterans Affairs Medical CenterLing Wei, Emory University
Language
  • English
Date
  • 2021-03-26
Publisher
  • Frontiers Media SA
Publication Version
Copyright Statement
  • © 2021 Jiang, Yu, Wei, Zhong, Cao, Gu, Wu, McCrary, Berglund and Wei.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 13
Start Page
  • 612856
End Page
  • 612856
Grant/Funding Information
  • The research was also supported by the O. Wayne Rollins Endowment fund, the Asa Griggs Candler Endowment fund (SY), and the John E. Steinhaus Endowment fund (LW).
  • We acknowledge the Viral Vector Core of Emory Neuroscience NINDS Core Facilities supported by an NIH grant P30NS055077.
  • AHA Career Development Award CDA34110317 (ZW); AHA Pre-doctoral Fellowship award AHA 0840110N (MJ).
  • This research was funded by NIH grants NS091585 (LW), NS099596 (LW/SY), NS114221 (LW/SY), S10 OD021773 (KB), Center for Integrated Healthcare, U.S. Department of Veterans Affairs; VA Merit grant RX001473 (SY), American Heart Association;
Supplemental Material (URL)
Abstract
  • The master neuronal transcription factor NeuroD1 can directly reprogram astrocytes into induced neurons (iNeurons) after stroke. Using viral vectors to drive ectopic ND1 expression in gliotic astrocytes after brain injury presents an autologous form of cell therapy for neurodegenerative disease. Cultured astrocytes transfected with ND1 exhibited reduced proliferation and adopted neuronal morphology within 2–3 weeks later, expressed neuronal/synaptic markers, and extended processes. Whole-cell recordings detected the firing of evoked action potentials in converted iNeurons. Focal ischemic stroke was induced in adult GFAP-Cre-Rosa-YFP mice that then received ND1 lentivirus injections into the peri-infarct region 7 days after stroke. Reprogrammed cells did not express stemness genes, while 2–6 weeks later converted cells were co-labeled with YFP (constitutively activated in astrocytes), mCherry (ND1 infection marker), and NeuN (mature neuronal marker). Approximately 66% of infected cells became NeuN-positive neurons. The majority (~80%) of converted cells expressed the vascular glutamate transporter (vGLUT) of glutamatergic neurons. ND1 treatment reduced astrogliosis, and some iNeurons located/survived inside of the savaged ischemic core. Western blotting detected higher levels of BDNF, FGF, and PSD-95 in ND1-treated mice. MultiElectrode Array (MEA) recordings in brain slices revealed that the ND1-induced reprogramming restored interrupted cortical circuits and synaptic plasticity. Furthermore, ND1 treatment significantly improved locomotor, sensorimotor, and psychological functions. Thus, conversion of endogenous astrocytes to neurons represents a plausible, on-site regenerative therapy for stroke.
Author Notes
Keywords
Research Categories
  • Biology, Neuroscience
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Rehabilitation and Therapy
  • Psychology, Cognitive
No preview available

Download the file

Tools

Relations

In Collection:

Items

Thumbnail Title File Description Date Uploaded Visibility Actions
file details Publication File - vv7f3.pdf Primary Content 2025-05-14 Public Download