Neurotrophic factors are polypeptides that regulate survival and differentiation of neural cells; a huge array of these neurotrophic factors are produced by glial cells. Particularly important are neurotrophins (the nerve growth factor, NGF; neurotrophins 3 and 4, NT-3, NT-4, and brain-derived neurotrophic factor, BDNF), which control a wide variety of CNS functions, from cell growth and differentiation, to synaptic transmission, regulation of ion channels expression and repair of neural circuits.
Glial cells produce and release growth factors in physiological conditions and upon neuronal damage. In the former case, growth factors derived from glia regulate various aspects of differentiation, growth and development of neural cells; whereas in the latter case, they help the processes responsible for regeneration and repair. In development, growth factors derived from glial cells regulate migration of neuronal precursors and immature neurones towards their final destiny, assist neuronal pathfinding, regulate appearance and remodelling of synaptic ensembles, and control ontogenetic nerve cell death. Astrocytes are the most prolific producers of growth factors; oligodendrocytes manufacture much less, but importantly they release netrin-1, which guides axonal pathfinding (and which is absent in astrocytes). Neuronal damage very much up-regulates production and release of growth factors especially from reactive astrocytes and activated microglial cells.
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