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Functional repair after ischemic injury through high efficiency in situ astrocyte-to-neuron conversion
- Publication Year :
- 2018
- Publisher :
- Cold Spring Harbor Laboratory, 2018.
-
Abstract
- Mammalian brains have largely lost internal neural regeneration capability except for a few discrete neurogenic niches. After brain injury, the cerebral cortex is especially difficult to repair due to its extremely low rate of adult neurogenesis. Previous studies have converted glial cells into neurons, but the total number of neurons generated is rather limited, casting doubt about its therapeutic potential. Here, we demonstrate that high-efficiency neuroregeneration can be achieved in adult mammalian brains by making use of an engineered AAV Cre-FLEX system to convert a large number of reactive astrocytes into functional neurons. Specifically, using a combination of GFAP::Cre and FLEX-NeuroD1 AAV system, we were able to regenerate enough new neurons from astrocytes to cover about 40% of the neurons lost from an ischemic injury (400 NeuN+ new neurons/mm2), compared to previously reported an average of
- Subjects :
- In situ
0303 health sciences
Neurogenesis
Ischemic injury
Biology
Neuroregeneration
03 medical and health sciences
0302 clinical medicine
medicine.anatomical_structure
nervous system
Cerebral cortex
medicine
biology.protein
Neuron
NeuN
Neuroscience
030217 neurology & neurosurgery
030304 developmental biology
Astrocyte
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....abdaa42ea25b8ef64004f5de075f5b79
- Full Text :
- https://doi.org/10.1101/294967