These effects are mirrored with respective changes in the frequency of γ-aminobutyric acid (GABA)ergic and glutamatergic synaptic inputs reflecting altered synaptic integration. The results suggest that miR-132 forms the basis of a structural plasticity program seen in SVZ-olfactory bulb postnatal neurogenesis. Cheng et al88 showed that miR-124 is an important regulator of the temporal progression of adult neurogenesis. They found that knockdown of endogenous miR-124 maintained purified SVZ stem cells as dividing precursors, whereas ectopic expression
led to precocious Inhibitors,research,lifescience,medical and increased neuron formation in mice. They identified the SRY-box transcription factor Sox9 as a physiological target of miR-1 24 during the transition from the transit-amplifying cell to the neuroblast stage. The overexpression of Sox9 abolished neuronal differentiation, whereas Sox9 knockdown led to increased neuron Inhibitors,research,lifescience,medical formation. Thus, miR-124-mediated repression of Sox9 is important for progression along the SVZ stem cell lineage to neurons. Bruno et al89 identified brain-specific miRNA: miR-128, that represses nonsense-mediated RNA decay machinery, which controls transcripts of a selleck inhibitor battery of target genes to regulate neurogenesis and neural differentiation. Inhibitors,research,lifescience,medical More recently, Åkerblom et al,90 using
a Inhibitors,research,lifescience,medical transgenic reporter mouse, found that miR-124 expression is initiated in the rapidly amplifying progenitors and remains expressed in the resulting neurons. Inhibition of miR-124 in vivo results in the blockade of neurogenesis, leading to the appearance of ectopic cells with astrocyte characteristics in the olfactory bulb. Conversely, neural stem cells are not maintained in the SVZ, when miR-124 is overexpressed, resulting in a loss of neurogenesis. These results suggest that miR-124 is a neuronal
fate determinant in the SVZ. miR-137, which is epigenetic ally regulated by DNA methyl-CpG-binding Inhibitors,research,lifescience,medical Mephenoxalone protein, can modulate proliferation and differentiation of adult neural stem cells such that overexpression of miR-137 promotes, whereas its reduction enhances proliferation of adult neural stem cells.91 Recently, Zhang et al92 identified a new cerebellum-enriched rno-miR-592, which plays an important role in embryonic neurogenesis and/or astrogliogenesis. By using gain-/loss-of-function approaches, they demonstrated that rno-miR-592 could change the balance between neuron- and astrocyte-like differentiation and neuronal morphology. miR-592 could induce astrogliogenesis differentiation arrest and/or enhance neurogenesis in vitro, whereas silencing of miR-592 was not beneficial for neuronal maturation.