Title : Brain microRNA and metabolic arrest
Abstract:
Unlike the brains of humans, animal brains are subject to extremes of environment – and must keep neural function intact during and after extreme conditions. Frogs and turtles totally freeze in winter, displaying no measurable brain activity and a flat-lined heart. Hibernating ground squirrels have brains that survive weeks at 0oC. Mole rats survive deep hypoxia/anoxia and maintain CNS function . These states are termed “suspended animation” and are characterized by global suppression of metabolic functions and the reprioritization of energy usage to essential survival processes . This extreme reorganization is elicited, in large part, by the regulatory controls of microRNAs. Our studies are the first to investigate miRNA biogenesis and regulation in extreme brains of vertebrates. The studies are informed by the creation and analyses of miRNA “OMES” – complete RNA-seq studies that have uncovered both up and down regulation of key microRNAs. These studies, coupled with quantitation of miRNA biogenesis factors, illustrated an overall reduction in the majority of these processing proteins - showing a potential suppression of miRNA maturation . Bioinformatic target enrichment of the up-and-downregulated miRNAs of each extreme brain predicted their involvement in the potential activation of various neuroprotective processes such as synaptic signaling, intracellular signal transduction, and anoxia/ischemia injury protection. The predominantly downregulated microRNA fingerprints identified in Nature, suggests a microRNA-mediated cytoprotective mechanism responsible for maintaining neuronal functions and facilitating successful whole brain metabolic rate depression [ MRD]. For deeper analyses , please see: http://www.kenstoreylab.com/
