Leukemia inhibitory factor (LIF) is a cytokine involved in the survival, differentiation and regeneration of sympathetic, sensory and motor neurons. Its effects in the brain are less well characterized. In a previous study, we found LIF transcripts to be predominantly expressed in neurons of the adult rat brain. Highest levels were observed in the hippocampus, particularly in granular neurons of the dentate gyrus and in hilar interneurons. Here we report the effects of LIF on survival and differentiation of postnatal rat hippocampal cells in vitro. We find that LIF minimally influences the survival and differentiation of dentate gyrus neurons, causing a slight reduction of the number of dendrites per neuron. In contrast, LIF induces a pronounced increase in the number of astrocytes. This increase does not appear to be due to enhanced proliferation but rather to increased cell survival. On the other hand, epidermal growth factor (EGF) induces astrocyte proliferation, and addition of LIF inhibits the EGF effect. In summary, LIF does not appear to be crucial for the survival or differentiation of cultured dentate gyrus neurons. This cytokine increases astrocyte survival but does not enhance astrocyte proliferation, and LIF is able to counteract the growth stimulation elicited by EGF.
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