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Conference by Adrien Meguerditchian

Published on March 28, 2017

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Direct lineage reprogramming of glial cells into functional neurons


Direct cellular reprogramming of non-neuronal cells into clinically relevant neurons emerges as a highly innovative strategy to regenerate lost neurons for brain repair. We and others previously showed that glial cells from the mouse cerebral cortex can be reprogrammed to generate functional neurons by forced expression of neurogenic transcription factors. One of the next challenge is to achieve in vivo reprogramming of somatic cells residing within the injured brain -in pathophysiological conditions- into fully functional neurons, that acquire the phenotype of lost neurons, functionally integrate into endogenous neuronal networks, and modulate the pathological network activity with beneficial effects. Our group has chosen to reprogram reactive glia residing within the epileptic brain into GABAergic induced neurons.
Epilepsy is a major clinical problem and >30% of epileptic patients suffer from pharmacoresistant seizures. In particular, Mesio-Temporal Lobe Epilepsy (MTLE), the most common form of intractable epilepsies, is characterized by recurrent seizures in the hippocampus. MTLE is associated with a proliferation of astroglia and a loss of GABAergic neurons in the hippocampus, which have been both suggested to participate in the increased neuronal excitability responsible for seizures. Therefore, we hypothesize that reprogramming reactive glial cells from the epileptic hippocampus into functional GABAergic neurons represents an innovative strategy to restore lost inhibitory transmission and ultimately reduce seizures.

KEYWORDS: Cellular reprogramming, astrocytes, NG2 glia, GABAergic neuron, Epilepsy.

Christophe Heinrich

Selected Publications of Team members :