Genomic and Epigenomic Responses to Chronic Stress Involve miRNA-Mediated Programming

Stress represents a critical influence on motor system function and has been shown to impair movement performance. We hypothesized that stress-induced motor impairments are due to brain-specific changes in miRNA and protein-encoding gene expression. Here we show a causal link between stress-induced motor impairment and associated genetic and epigenetic responses in relevant central motor areas in a rat model. Exposure to two weeks of mild restraint stress altered the expression of 39 genes and nine miRNAs in the cerebellum. In line with persistent behavioural impairments, some changes in gene and miRNA expression were resistant to recovery from stress. Interestingly, stress up-regulated the expression of Adipoq and prolactin receptor mRNAs in the cerebellum. Stress also altered the expression of Prlr, miR-186, and miR-709 in hippocampus and prefrontal cortex. In addition, our findings demonstrate that miR-186 targets the gene Eps15. Furthermore, we found an age-dependent increase in EphrinB3 and GabaA4 receptors. These data show that even mild stress results in substantial genomic and epigenomic changes involving miRNA expression and associated gene targets in the motor system. These findings suggest a central role of miRNA-regulated gene expression in the stress response and in associated neurological function

Large variation of vacancy formation energies in the surface of crystalline ice

Resolving the atomic structure of the surface of ice particles within clouds, over the temperature range encountered in the atmosphere and relevant to understanding heterogeneous catalysis on ice, remains an experimental challenge. By using first-principles calculations, we show that the surface of crystalline ice exhibits a remarkable variance in vacancy formation energies, akin to an amorphous material. We find vacancy formation energies as low as similar to 0.1-0.2 eV, which leads to a higher than expected vacancy concentration. Because a vacancy's reactivity correlates with its formation energy, ice particles may be more reactive than previously thought. We also show that vacancies significantly reduce the formation energy of neighbouring vacancies, thus facilitating pitting and contributing to pre-melting and quasi-liquid layer formation. These surface properties arise from proton disorder and the relaxation of geometric constraints, which suggests that other frustrated materials may possess unusual surface characteristics

Behavioral and neurochemical changes induced by oxycodone differ between adolescent and adult mice.

Nonmedical use of the prescription opioid analgesic oxycodone is a major problem in the United States, particularly among adolescents and young adults. This study characterized self-administration of oxycodone by adolescent and adult mice, and how this affects striatal dopamine levels. Male C57BL/6J mice (4 or 10 weeks old) were allowed to acquire oxycodone self-administration (0.25 mg/kg per infusion) for 9 days, and then tested with varying doses of oxycodone (0, 0.125, 0.25, 0.5, and 0.75 mg/kg per infusion). On completion of the self-administration study, a guide cannula was implanted into the striatum of these mice. Six days later, microdialysis was conducted on the freely moving mouse. After collection of baseline samples, oxycodone was administered i.p. (1.25, 2.5, and 5.0 mg/kg) and samples were collected for 1 h after each dose. Adult mice self-administered significantly more oxycodone across the doses tested. After 1 week, basal striatal dopamine levels were lower in mice of both ages that had self-administered oxycodone than in yoked saline controls. Oxycodone challenge increased striatal dopamine levels in a dose-dependent manner in both age groups. Of interest, the lowest dose of oxycodone led to increased striatal dopamine levels in the mice that had self-administered oxycodone during adolescence but not those that self-administered it as adults. The lower number of infusions of oxycodone self-administered by adolescent mice, and their later increased striatal dopamine in response to the lowest dose of oxycodone (not found in adults), suggest differential sensitivity to the reinforcing and neurobiological effects of oxycodone in the younger mice