Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
03
07
2020
accepted:
29
04
2021
pubmed:
5
6
2021
medline:
18
9
2021
entrez:
4
6
2021
Statut:
ppublish
Résumé
Methods to enhance adult neurogenesis by reprogramming glial cells into neurons enable production of new neurons in the adult nervous system. Development of therapeutically viable approaches to induce new neurons is now required to bring this concept to clinical application. Here, we successfully generate new neurons in the cortex and dentate gyrus of the aged adult mouse brain by transiently suppressing polypyrimidine tract binding protein 1 using an antisense oligonucleotide delivered by a single injection into cerebral spinal fluid. Radial glial-like cells and other GFAP-expressing cells convert into new neurons that, over a 2-month period, acquire mature neuronal character in a process mimicking normal neuronal maturation. The new neurons functionally integrate into endogenous circuits and modify mouse behavior. Thus, generation of new neurons in the dentate gyrus of the aging brain can be achieved with a therapeutically feasible approach, thereby opening prospects for production of neurons to replace those lost to neurodegenerative disease.
Identifiants
pubmed: 34083786
doi: 10.1038/s41593-021-00864-y
pii: 10.1038/s41593-021-00864-y
pmc: PMC8338913
mid: NIHMS1720443
doi:
Substances chimiques
Oligonucleotides, Antisense
0
Polypyrimidine Tract-Binding Protein
139076-35-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1089-1099Subventions
Organisme : NINDS NIH HHS
ID : R37 NS027036
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : BLRD VA
ID : I01 BX003759
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109885
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH108528
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS027036
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS105969
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH100175
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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