Genetic analyses have linked MicroRNA-137 (
MIR137
) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder (ASD). MiR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss of function
in vivo
remains unclear. Here we show the complete loss of miR-137 in the mouse germline (gKO) or nervous system (cKO) leads to postnatal lethality, while heterozygous gKO and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, Phosphodiesterase 10a (Pde10a), is elevated in heterozygous KO mice. Treatment with the PDE10A inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that
MIR137
plays essential roles in postnatal neurodevelopment, and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans.
To develop a new practical method of purifying and recycling ionic liquids, we performed direct microscopic observations and in situ crystallization of low-melting ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF(6)]), in detail by high pressure Raman spectroscopy. Compression of [BMIM][PF(6)] was measured under pressures up to about 2.0 GPa at temperatures 293-353 K by using a high pressure diamond anvil cell (DAC). At room temperature, with pressure increasing, the characteristic bands of [BMIM][PF(6)] displayed nonmonotonic pressure-induced frequency shifts, and [BMIM][PF(6)] experienced the liquid-solid phase transition at about 0.50 GPa. In separate experiments, in situ crystallization of low-melting ionic liquid [BMIM][PF(6)] were also measured at various P-T regions, in order to improve the understanding of its stability limits. Finally, the T versus P phase diagram of [BMIM][PF(6)] was constructed, and it showed that the melting point was an increase function of pressure. It was also indicated that the structure changes in the crystalline and liquid states under high pressure might also be associated with conformational changes in the butyl chain. Pressure-released Raman spectra also showed that the phase transition of [BMIM][PF(6)] was reversible.
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