Deficiency of TREK‐1 potassium channel exacerbates secondary injury following spinal cord injury in mice

Abstract

Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI. TREK-1 was widely expressed in mice spinal cord, including astrocytes and neurons. Deficiency of TREK-1 significantly exacerbated focal inflammatory responses as indicated by the increased accumulation of microglia/macrophage as well as pro-inflammatory factor interleukin-1 beta (IL-1β) and tumor necrosis factor alpha expression. Meanwhile, TREK-1 knockout mice showed enhanced reactive astrogliosis, chondroitin sulphate proteoglycans (CSPGs) production and decreased glutamate transporter-1 expression compared to the wide-type mice after SCI. Furthermore, TREK-1 deficiency promoted neurons and oligodendrocytes apoptosis, aggravated demyelination, cavity formation and retarded motor recovery. In summary, our findings provide the first in vivo evidence suggesting that TREK-1 may thereby constitute a promising therapeutic target to treat acute SCI.

Oligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: The forgotten partner

“…Finally, different ion channels are expressed in OPCs and oligodendrocytes including voltage-gated sodium channels (Tong et al, 2009), voltate-gated calcium channels (Verkhratsky et al, 1990) and diverse potassium channels (Buttigieg et al, 2011;Wang et al, 2011;Hawkins and Butt, 2013;Moroni et al, 2015;Battefeld et al, 2016;Livesey et al, 2016;Fang et al, 2017;Brasko et al, 2017;Larson et al, 2018) which participate in glial cell proliferation, regeneration, oligodendroglia/neuronal and axonal interactions, and Ferrer Progress in Neurobiology xxx (2018) xxx-xxx which modulate oligodendroglial responses to ischemia, excitotoxicity and seizures, among other pathological settings.…”

Effects of sevoflurane on rats with ischemic brain injury and the role of the TREK-1 channel

“…TREK-1 channel, which is a novel subtype of two-pore-domain potassium channels, can be activated by mechanical stretch and polyunsaturated fatty acids. Numerous studies have reported that TREK-1 (mainly expressed in brain and spinal cord) channel plays a neuroprotective effect in the process of cerebral ischemic injury ( 14 , 15 ). Treatment with TREK-1 channel agonists can effectively reduce brain damage in animal models of cerebral ischemia and epilepsy, while brain damage cannot be reduced in TREK-1 knockout rats ( 16 ).…”

Role of TREK-1 in Health and Disease, Focus on the Central Nervous System

“…TREK-1 deficient mice showed an exacerbated focal inflammatory response after spinal cord injury (SCI). Furthermore, TREK-1 deficiency enhanced astrogliosis, neuronal apoptosis, demyelination and retarded motor recovery (Fang et al, 2017). Nevertheless, in other reported studies, in the DRG, the microRNA miR-183 expression was decreased and TREK-1 expression was increased in neuropathic pain induced by chronic constriction of sciatic nerve (CCI) (Table 3; Han et al, 2016; Shi et al, 2018).…”