Browsing by Subject "miRNAs"
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Item Determine the spatial and temporal expression patterns of Drosophila miRNAs(2007-12) Ao, Xue, 1977-; Macdonald, Paul M.microRNAs (miRNAs), are a class of small (21-23nt), endogenous, non-coding RNAs which regulate gene expression. In animals, most miRNAs recognize their mRNA targets though imperfect base paring with complementary sites at the 3’UTR of the mRNAs, resulting in translational repression of the target genes. The specific functions of miRNAs in Drosophila are generally unknown. To determine the spatial and temporal expression patterns of miRNAs, it is necessary to identify both the sites and time of miRNA action and further elucidate miRNA functions. I made a series of GFP reporter transgenes (miRNA sensors) in UAS vector containing multiple copies of synthesized miRNA targets in the 3’UTR. The sensors were expressed in a range of tissues driven by different GAL4 drivers. We expected that our sensors would reveal when and where miRNAs are actively regulate gene expression. However, the sensor strategy failed to detect clear expression patterns of the miRNAs we tried.Item MicroRNA Dysregulation Following Spinal Cord Contusion: Implications for Neural Plasticity and Neuropathic Pain(2013-05-30) Strickland, EricSpinal cord injury (SCI) results in a number of devastating consequences, including loss of motor function, paralysis, and neuropathic pain. Concomitant peripheral tissue injury below the lesion site can result in uncontrollable nociception that sensitizes spinal neurons and promotes chronic pain. Additionally, drugs like morphine, though critical for pain management, elicit pro-inflammatory effects that exacerbate chronic pain symptoms. Currently, there is a lack of effective therapeutic mechanisms to promote regeneration at the lesion site, and a limited understanding of regulatory mechanisms that can be utilized to therapeutically manipulate spinal cord plasticity. MicroRNAs (miRNAs) constitute novel targets for therapeutic intervention to both promote repair and regeneration, and mitigate maladaptive plasticity that leads to neuropathic pain. Microarray and qRT-PCR comparisons of contused and sham rat spinal cords at 4 and 14 days following SCI indicated that a total of 35 miRNAs were dysregulated, with miR1, miR124, and miR129 exhibiting significant down-regulation after SCI, and both miR21 and miR146a being transiently induced. Localized expression of miRNAs and cellular markers indicated that changes in miRNA regulation favor the emergence of neural stem cell niches and reversion of surviving neurons to a pre-neuronal phenotype. Additionally, both uncontrollable nociception and morphine administration resulted in further dysregulation of SCI-sensitive miRNAs, along with their mRNA targets. Morphine administration significantly induced expression of both miR21 and IL6R expression, indicating that morphine-induced miRNA dysregulation is involved in the promotion of neuroinflammation that drives increased pain-sensitivity. Similarly, uncontrollable nociception significantly modulates expression of miR124, miR129, and miR146a, which inhibit cell cycle proteins and microglial activation, and dysregulation of these miRNAs, along with BDNF and IGF-1, likely contributes towards promotion of hypersensitivity in spinal neurons that underlies neuropathic pain. Consequently, SCI- sensitive miRNAs may constitute therapeutic targets for modulation of neuroinflammation and microglial activation in order to mitigate secondary injury, promote regeneration, and prevent maladaptive plasticity that drives neuropathic pain and exacerbation of chronic pain symptoms by morphine administration.