The proto-oncogene bcl-2 and its family members, bcl-x and bax are recognized as major regulators of cell death and survival. Although Bcl-2 and Bcl-x are expressed in brain, little is known how they are regulated in neurons. Here we have studied the expression of bcl-2, bcl-xL and bax mRNA in rat cerebellar granule neurons cultured under conditions which influence neuron survival. Insulin-like growth factor-1 and brain-derived neurotrophic factor supported the survival of these neurons, but affected neither the expression of bcl-2, bcl-xL nor bax mRNA. In contrast, bcl-2 and bcl-xL mRNAs were up-regulated in cerebellar granule neurons plated at high density exhibiting an increased neuronal survival. Western blots showed that cell density also increased Bcl-2 protein level. However, conditioned medium from dense cultures did not affect the level of bcl-2 mRNA nor survival of the neurons. This suggests that cell density promotes survival and regulates Bcl-2 expression in cerebellar granule neurons through a signaling pathway different from known neurotrophic factors.
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