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Human-Derived Induced GABAergic Progenitor Cells Improve Cognitive Function in Mice and Inhibit Astrocyte Activation with Anti-Inflammatory Exosomes.
- Source :
-
Annals of neurology [Ann Neurol] 2024 Sep; Vol. 96 (3), pp. 488-507. Date of Electronic Publication: 2024 Jun 11. - Publication Year :
- 2024
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Abstract
- Objective: The role of gamma-aminobutyric acid-ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown.<br />Methods: Human-derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP).<br />Results: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin-1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD-related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti-inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4 <superscript>+</superscript> Th1 cells mediated tumor necrosis factor (TNF) pathway.<br />Interpretation: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti-inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488-507.<br /> (© 2024 American Neurological Association.)
Details
- Language :
- English
- ISSN :
- 1531-8249
- Volume :
- 96
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Annals of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 38860520
- Full Text :
- https://doi.org/10.1002/ana.27001