Abstract
TWIK (tandem-pore domain weak inward rectifying K+)-related spinal cord K+ channel (TRESK), a member of the two-pore domain K+ channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression is changed in several models of peripheral nerve injury, resulting in a shift in sensory neuron excitability. However, the role of TRESK in the model of spinal cord injury (SCI) has not been fully understood. This study investigates the role of TRESK in a thoracic spinal cord contusion model, and in transgenic mice overexpressed with the TRESK gene (TGTRESK). Immunostaining analysis showed that TRESK was expressed in the dorsal and ventral neurons of the spinal cord. The TRESK expression was increased by SCI in both dorsal and ventral neurons. TRESK mRNA expression was upregulated in the spinal cord and DRG isolated from the ninth thoracic (T9) spinal cord contusion rats. The expression was significantly upregulated in the spinal cord below the injury site at acute time points (6, 24, and 48 h) after SCI (p < 0.05). In addition, TRESK expression was markedly increased in DRGs below and adjacent to the injury site. TRESK was expressed in inflammatory cells. In addition, the number and fluorescence intensity of TRESK-positive neurons increased in the dorsal and ventral horns of the spinal cord after SCI. TGTRESK SCI mice showed faster paralysis recovery and higher mechanical threshold compared to wild-type (WT)-SCI mice. TGTRESK mice showed lower TNF-α concentrations in the blood than WT mice. In addition, IL-1β concentration and apoptotic signals in the caudal spinal cord and DRG were significantly decreased in TGTRESK SCI mice compared to WT-SCI mice (p < 0.05). These results indicate that TRESK upregulated following SCI contributes to the recovery of paralysis and mechanical pain threshold by suppressing the excitability of motor and sensory neurons and inflammatory and apoptotic processes.
Highlights
Spinal cord injuries (SCIs) result in many biomedical and molecular changes
Single-channel recordings were performed in postnatal rat day 1 or day 2 (P1-2) dorsal root ganglion (DRG) neurons ranging from 10 to 38 μm in diameter
TRESK mRNA expression levels were significantly decreased in adult DRG (P120) by 80% compared to neonatal DRG (P1-2) (n = 5, p < 0.05, Figure 1C)
Summary
A primary injury, which consists of severed axons, dying neurons, and glia, and a disturbed microvasculature, triggers a cascade of pathological events, including vascular and biochemical changes, free radical formation, local acidosis, hemorrhagic necrosis, and inflammatory processes [1,2,3,4]. These changes result in severe motor and sensory dysfunctions, such as paralysis and pain, which is a serious and common problem after an SCI [5]. The spinal contusion is the oldest and most widely used SCI animal model
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