title: Regulatory effects of intermittent noxious stimulation on spinal cord injury-sensitive microRNAs and their presumptive targets following spinal cord contusion.
abstract: Uncontrollable nociceptive stimulation adversely affects recovery in spinally contused rats. Spinal cord injury (SCI) results in altered microRNA (miRNA) expression both at, and distal to the lesion site. We hypothesized that uncontrollable nociception further influences SCI-sensitive miRNAs and associated gene targets, potentially explaining the progression of maladaptive plasticity. Our data validated previously described sensitivity of miRNAs to SCI alone. Moreover, following SCI, intermittent noxious stimulation decreased expression of miR124 in dorsal spinal cord 24 h after stimulation and increased expression of miR129-2 in dorsal, and miR1 in ventral spinal cord at 7 days. We also found that brain-derived neurotrophic factor (BDNF) mRNA expression was significantly down-regulated 1 day after SCI alone, and significantly more so, after SCI followed by tailshock. Insulin-like growth factor-1 (IGF-1) mRNA expression was significantly increased at both 1 and 7 days post-SCI, and significantly more so, 7 days post-SCI with shock. MiR1 expression was positively and significantly correlated with IGF-1, but not BDNF mRNA expression. Further, stepwise linear regression analysis indicated that a significant proportion of the changes in BDNF and IGF-1 mRNA expression were explained by variance in two groups of miRNAs, implying co-regulation. Collectively, these data show that uncontrollable nociception which activates sensorimotor circuits distal to the injury site, influences SCI-miRNAs and target mRNAs within the lesion site. SCI-sensitive miRNAs may well mediate adverse consequences of uncontrolled sensorimotor activation on functional recovery. However, their sensitivity to distal sensory input also implicates these miRNAs as candidate targets for the management of SCI and neuropathic pain.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center Bryan, TX, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Strickland
authors.affiliation: Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Woller
authors.affiliation: Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Garraway
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center Bryan, TX, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hook
authors.affiliation: Department of Psychology, Texas A&M University, College Station TX, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Grau
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center Bryan, TX, USA.
authors.forename: Rajesh C
authors.initials: RC
authors.lastname: Miranda
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D059225:Nociception / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013223:Statistics as Topic
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D035683:MicroRNAs; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I
keywords: BDNF; IGF; microRNA; spinal cord injury; uncontrollable nociception