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Publication : Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB.

First Author  Maimon R Year  2021
Journal  Nat Neurosci Volume  24
Issue  8 Pages  1089-1099
PubMed ID  34083786 Mgi Jnum  J:323400
Mgi Id  MGI:7263118 Doi  10.1038/s41593-021-00864-y
Citation  Maimon R, et al. (2021) Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB. Nat Neurosci 24(8):1089-1099
abstractText  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.
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