Background and Purpose - Loss of neurons after brain injury and in neurodegen-erative disease is often accompanied by reactive gliosis and scarring, which are difﬁcult to reverse with existing treatment approaches. Here, we show that reactive glial cells in the cortex of stab-injured or Alzheimer’s disease (AD) model mice can be
directly reprogrammed into functional neurons in vivo using retroviral expression of a single neural transcription factor, NeuroD1.
Methodology and Results--Following expression of NeuroD1, astrocytes were reprogrammed into glutamatergic neurons, while NG2 cells were reprogrammed into glutamatergic and GABAergic neurons.Cortical slice recordings revealed both spontaneous and evoked synaptic responses in NeuroD1-converted neurons, suggesting that they integrated into local neural circuits. NeuroD1 expression was also able to reprogram cultured human cortical astro-
cytes into functional neurons.
Conclusions— Our studies therefore suggest that direct reprogramming of reactive glial cells into functional neurons in vivo could provide an alternative approach for repair of injured or diseased brain.