Abstract
Nerve growth factor (NGF) synthesis and secretion from astrocytes is cooperatively regulated by various cytokines including fibroblast growth factors, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). The present study was performed to determine the effect of NGF produced by cytokine-activated astrocytes on NGF-deprived septal neurons in vitro. Enzymatically dissociated septal neurons from E-16 rat fetuses were grown on monolayered astrocytes obtained from neonatal rat hippocampi in a serum-free defined medium. Effects of the various combinations of IL-1 β, TNF-α and TGF-β1 on septal cholinergic neurons cocultured with astrocytes were examined. A combination of IL-1β and TNF-α increased choline-acetyltransferase (CAT) activity via NGF produced by astrocytes. NGF-treated septal cholinergic neurons were found to degenerate following NGF deprivation. However, a combination of IL-1β and TNF-α significantly reduced the degeneration of NGF-deprived septal cholinergic neurons by activating astrocytes. The cytokines, which regulate NGF synthesis and secretion in astrocytes, are considered to play an important role in neuronal regeneration following brain injury.
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