Neurogenesis from Neuroglia: Role of Epidermal Growth Factor in Neuroglial Transdifferentiation into Neuronal Precursor Cells

Abstract

In the adult, neurogenesis occurs primarily in the hippocampus, olfactory bulb, and subventricular zone. Unlike neurons, neuroglia proliferate throughout life in response to brain aging and damage. We investigated the role of Epidermal Growth Factor (EGF) in transdifferentiating neuroglia into precursor cells and eventually neurons. C6 rat glioma cells, a mixture of astrocyte and oligodendrocytes, was treated with 50ng/mL EGF for 30 days. EGF increases proliferation, but reduces overtime the activity of Glutamine Synthetase (GS) and 2′3′‐cyclic nucleotide 3′ phosphohydrolase (CNP), the enzyme markers for astrocytes and oligodendrocytes, respectively. Simultaneously, immunofluoresence imaging showed that after 14 days of EGF treatment, neuroglial cells expressed the neuronal marker, Nestin. By 21 days, electrophysiological recordings show a resting membrane potential resembling that of neurons rather than that of neuroglia and some isolated action spikes. Thus, EGF treatment of neuroglial cells induces dedifferentiation of these cells and their transdifferentiation to exhibit certain neuronal characteristics. Supported by NIH Grant AG 19145‐05.