Morphine Promotes Astrocyte-Preferential Differentiation of Mouse Hippocampal Progenitor Cells via PKCε-Dependent ERK Activation and TRBP Phosphorylation

• DOI: 10.1002/stem.2055
• Publication Date: 2015-05-26T23:12:32Z
• Authors: Chi Xu; Hui Zheng; Horace H. Loh; Ping-Yee Law
• Keywords: Dicer

Previously we have shown that morphine regulates adult neurogenesis by modulating miR-181a maturation and subsequent hippocampal neural progenitor cell (NPC) lineages. Using NPCs cultured from PKCε or β-arrestin2 knockout mice the MAPK/ERK kinase inhibitor U0126, demonstrate regulation of NPC differentiation via miR-181a/Prox1/Notch1 pathway exhibits ligand-dependent selectivity. In NPCs, fentanyl activate ERK PKCε- β-arrestin-dependent pathways, respectively. After exposure, activated phospho-ERK translocates to nucleus. Conversely, after treatment, remains in cytosol is capable phosphorylating TAR RNA-binding protein (TRBP), a cofactor Dicer. This augments Dicer activity promotes miR-181a. Furthermore, using transfected with wild-type TRBP, SΔA, SΔD TRBP mutants, confirmed crucial role phosphorylation activity, maturation, finally morphine-induced astrocyte-preferential NPCs. Thus, modulates lineage-specific PKCε-dependent activation maturation.