FIG. 1.

Effects of TNFα on NSPC activity. TNFα treatment results in disparities in differentiation because of the subtype of TNFR (TNFR1 or TNFR2) and the age/brain region of the NSPCs. In the adult dentate gyrus (DG), TNFα induces increased neurogenesis in NSPCs through TNFR2 binding. No changes in differentiation are observed when TNFα binds to TNFR1 in the same model. In postnatal SVZ NSPCs, TNFα activates the SAPK/JNK pathway through TNFR1, resulting in increased neurogenesis. Many studies do not address the relative roles of TNFR1/TNFR2 specifically, but rather focus on intracellular signaling pathways that are activated by TNFα. In embryonic hippocampal NSPCs, TNFα results in astrogliogenesis through the activation of Hes1, an antineurogenic transcription factor. Chronic TNFα treatment results in increased expression of the proapoptotic protein, Bax, which is accompanied by activation/cleavage of caspase-3 in NSPCs. In contrast, acute TNFα treatment results in increased proliferation through NF-κB signaling. TNFα also leads to the release of LIF that activates STAT3 signaling through LIFR and promotes astrogliogenesis in NSPCs. Solid lines represent pathways that are defined in the literature, and the dotted line represents a proposed pathway. Bax, B cell lymphoma 2 associated protein; Hes1, Hairy and enhancer of split-1; LIF, leukemia inhibitory factor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NSPCs, neural stem/progenitor cells; SAPK/JNK, stress activated protein kinase/c-Jun N-terminal kinase; SVZ, subventricular zone; TNFα, tumor necrosis factor alpha.