Loose ligation of the sciatic nerve in rats elicits transient up-regulation of Homer1a gene expression in the spinal dorsal horn.
Changes in the expression of many genes underlie injury-elicited plasticity in the spinal dorsal horn. Homer1 is a recently identified gene that appears to play a critical role in the expression of synaptic plasticity in several brain regions, including the hippocampus. In this study we investigated the early consequences of chronic constriction injury of the sciatic nerve on Homer1 gene expression in the spinal dorsal horn. Significant increases in Homer1a mRNA levels in the ipsilateral dorsal horn were detected at 4h post-ligation, and these levels remained elevated at 8h before returning to baseline values by 24h after the ligation. In contrast, the levels of Homer1b/c mRNA did not change at any of these selected post-ligation times. The ligation-associated induction of Homer1a was dependent on activation of NMDA receptors and the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway. The non-competitive NMDA-receptor antagonist, MK-801, and a specific inhibitor of the ERK1/2 pathway, U0126, significantly attenuated the injury-elicited increases in Homer1a mRNA when compared to saline-treated animals. These data provide the first evidence for a potential role of Homer1a in peripheral nerve injury-elicited plasticity in the spinal dorsal horn. These data also imply that the early and transient up-regulation of Homer1a gene expression may be an important contributor to the eventual development of neuropathic pain.
Miyabe
Takako
T
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706-1102, USA.
Miletic
Gordana
G
Miletic
Vjekoslav
V
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D003251:Constriction, Pathologic; D016291:Dizocilpine Maleate / Q000494:pharmacology; D000072233:Homer Scaffolding Proteins; D008026:Ligation; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D009473:Neuronal Plasticity; D009570:Nitriles / Q000494:pharmacology; D010146:Pain / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D012584:Sciatic Nerve / Q000293:injuries; D015854:Up-Regulation
D002070:Butadienes; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606624:Homer1 protein, rat; D009570:Nitriles; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C113580:U 0126; D016291:Dizocilpine Maleate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3