Stage-dependent STAT3 activation is involved in the differentiation of rat hippocampus neural stem cells.

Extracts of deafferented hippocampus were previously found to promote neuronal differentiation of neural stem cells (NSCs). To gain insights into the underlying molecular mechanisms we studied the potential involvement of signal transducer and activator of transcription3 (STAT3) activation in the NSCs response to hippocampal extracts. Here we report that phosphorylated STAT3 (p-STAT3) is expressed at different stages in neurons and astrocytes differentiated from rat hippocampus-derived NSCs. Deafferented hippocampal extracts produced sustained upregulation of p-STAT3 levels and promoted NSC differentiation and neurogenesis, whereas extracts of normal hippocampus were without effect. Interleukin-6 (IL-6), an activator of JAK/STAT signaling pathways, had no effect on neurogenesis, whereas the selective STAT3 inhibitor p-ip-STAT3 decreased the number of Microtubule-associated protein-2 (MAP-2)-positive cells generated by NSC differentiation. These findings argue that STAT3-related signaling pathways are likely to play a role in neuronal survival and differentiation during NSC neurogenesis stimulated by extracts of deafferented hippocampus.