Ablation of the microRNA‐17‐92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function. Issue 4 (22nd January 2019) - Pan, Wan Long
ABSTRACT: Impairment of adult neurogenesis in the hippocampus causes cognitive deficits; however, the underlying molecular mechanisms have not been fully elucidated. microRNAs (miRNAs) regulate neural stem cell (NSC) function. With the use of a transgenic mouse line with conditional ablation of the miR‐17‐92 cluster in nestin lineage NSCs, we tested the hypothesis that the miR‐17‐92 cluster regulates adult neurogenesis and cognitive function in vivo . Compared with wild‐type mice, ablation of the miR‐17‐92 cluster significantly reduced the number of proliferating NSCs and neuroblasts and neuronal differentiation in the dentate gyrus (DG) of the hippocampus and significantly impaired hippocampal‐dependent learning and memory, as assayed by social recognition memory, novel object recognition, and Morris water‐maze tests. Statistical analysis showed a highly significant correlation between newly generated neuroblasts in the DG and cognition deficits in miR‐17‐92 knockout (KO) mice. Western blot analysis showed that conditional KO of the miR‐17‐92 cluster significantly increased and reduced a cytoskeleton‐associated protein, Enigma homolog 1 (ENH1), and its downstream transcription factor, inhibitor of differentiation 1 (ID1), respectively, as well as increased phosphatase and tensin homolog gene. These proteins are related to neuronal differentiation. Our study demonstrates that the miR‐17‐92 cluster in NSCs is critical for cognitive and behavioral function and regulates neurogenesis and that the miR‐17‐92 cluster may target ENH1/ID1 signaling.—Pan, W. L., Chopp, M., Fan, B., Zhang, R., Wang, X., Hu, J., Zhang, X. M., Zhang, Z. G., Liu, X. S. Ablation of the microRNA‐17‐92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function. FASEB J. 33, 5257–5267 (2019). www.fasebj.org