Cytokine Control of Adult Neural Stem Cells Chronic versus Acute Exposure

The neuropoietic cytokine family includes interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF), among others. These cytokines have been shown to alter neural stem cell (NSC) self-renewal and progenitor cell division and differentiation, which could be mediated by the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. Using neurospheres from the adult mouse subventricular zone (SVZ), we found that acute or chronic exposure to LIF or CNTF differentially affects sphere development and sphere growth. Both cytokines also favor the amplification of NSCs. Contrasting results were obtained with IL-6 or leptin, although both cytokines also activate the JAK/STAT pathway. Stimulating NSC self-renewal in vivo could be of therapeutic interest for treating neurodegeneration. When applied to the adult mouse brain, chronic LIF stimulates NSC self-renewal but prevents the emergence of more differentiated progeny. On the other hand, acute LIF treatment stimulates SVZ regeneration, most likely through an increase in NSCs. These results reveal that cytokine effects could vary as a function of exposure duration and suggest that, in the search for strategies to promote brain repair, in vivo acute LIF treatment could promote cell replacement.