Arachidonic acid has protective effects on oxygen-glucose deprived astrocytes mediated through enhancement of potassium channel TREK-1 activity

Lü, Li; Zhang, Guangru; Song, Chunli; Wang, Xuexi; Qian, Weina; Wang, Zhuanling; Liu, Yanan; Gong, Shi-Cai; Zhou, Shuning

doi:10.1016/j.neulet.2016.11.034

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…Consistent with this, we also showed the similar changes with increased Glu content and decreased level of GLT-1 which indicated the formation of neurodegenerative changes in SAMP8 mice. TREK-1 has been con rmed to take part in regulation of GLT-1 activity (Lu et al 2017). In cerebral ischemia, TREK-1 regulated GLT-1 activity and improved synaptic connections (Lalo et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…It mediated the release of Glu by astrocytes to regulate the synaptic connection between astrocytes and neuron (Lalo et al 2014 ;Woo et al 2012). AA exert protective effect on oxygen-glucose deprived astrocytes by increasing glutamate reuptake (Lu et al 2017). The accumulation of Glu leads to over-activation of NMDAR, resulting in neuronal damage (Ota et al 2015).…”

Section: Morphological Changesmentioning

confidence: 99%

“…Neuroprotection of PUFAs was closely involved in TREK-1 channels, for example, TREK-1 -/mice display an increased sensitivity to ischemia and (Heurteaux et al 2004) neuroprotection disappear after ALA treatment (Liu et al 2014). Through activation of TREK-1, ALA hyperpolarizes the resting membrane potential of astrocytes and up-regulates the decreased of GLT-1 protein level induced by focal ischemia (Lu et al 2017). Besides, the neuroprotection of volatile anesthetics is mediated by TREK-1 and further concerned with the inhibition of NMDAR (Bittner et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Activation of TREK-1 Potassium Channel Improved Cognitive Deficits in Alzheimer's Disease Model Mice by Modulation of Glutamate Metabolic Pathway

Zhou

Zeng

et al. 2021

Preprint

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Alzheimerʼs disease (AD) is a progressive neurodegenerative disease characterized by cognitive dysfunction. Glutamate (Glu) metabolism pathway mediated neurotoxicity is one of main factors causing memory impairment in AD. TWIK-related potassium channel-1 (TREK-1) exerts protective effect in brain ischemia, but the role of it in AD is unknown. In this study, the SAMP8 mice were used as an AD model, the age-matched SAMR1 mice as a control, we investigated the change trend of TREK-1 channel as well as AD related molecules in brains of SAMP8 mice and showed the expression levels of TREK-1 compensatory arose before 3 months of age, then began to decline. Meanwhile the levels of Tau and Glu increased with age while Ach level decreased over age. Next, using α-Linolenic acid (ALA) as an activator of TREK-1 channel, we showed that activation of TREK-1 channel improved the learning and memory deficits of SAMP8 mice aged in 6 months. Furthermore, we explored the possible mechanisms and found that the levels of molecules were closely related to the glutamate metabolism pathway. After the activation of TREK-1 channel, the damaged neurons and astrocyte were rescued, the levels of Glu and NMDAR were down-regulated, while the level of GLT-1 was up-regulated. These findings suggested that TREK-1 played the crucial role in the pathological progression of AD and activation of TREK-1 channel improved the cognitive deficits in SAMP8 mice which is mediated by Glu metabolism pathway. The TREK-1 potassium channel may be expected to be a new potential therapeutic target for AD.

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Section: Discussionmentioning

confidence: 99%

Section: Morphological Changesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of TREK-1 Potassium Channel Improved Cognitive Deficits in Alzheimer's Disease Model Mice by Modulation of Glutamate Metabolic Pathway

Zhou

Zeng

et al. 2021

Preprint

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

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

Pan

Yang

Lü

et al. 2017

Experimental and Therapeutic Medicine

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The purpose of this investigation was to determine the effects of sevoflurane on rats with ischemic brain injury and to determine the potential role of the TREK-1 channel in this process. Normal rats were randomly divided into three groups: Sham operation, sevoflurane anesthesia or chloral hydrate anesthesia group, an additional group of TREK-1 knockout rats were also studied. Semi-quantitative PCR and western blot analysis confirmed the lack of TREK-1 expression in the brain of TREK-1 knockout rats. The thread-tie method was used to establish middle cerebral artery occlusion (MCAO) model to induce cerebral ischemic brain injury. All rates were treated for 4 days prior to ischemia (for 2 h) followed by a 24 h reperfusion period. Physiological indexes of rats in each group both prior to and after surgery showed no statistical difference (P>0.05). Neurological function was scored both before (no statistical difference) and after surgery where it was found to be significantly better (lower score) in the sevoflurane anesthesia group than in chloral hydrate anesthesia and TREK-1 knockout groups (P<0.01). The area of cerebral infarction was measured by triphenyl tetrazolium chloride staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect the apoptosis of brain cells. TTC staining showed different degrees of cerebral infarction in the various groups; the area of cerebral infarction in sevoflurane anesthesia group was significantly lower than that in chloral hydrate anesthesia and TREK-1 knockout groups (P<0.01). TUNEL assay showed that the number of TUNEL-positive cells was significantly lower in sevoflurane anesthesia group than in TREK-1 knockout and chloral hydrate anesthesia groups (P<0.01). In conclusion, results from this investigation showed that sevoflurane can protect the nerve function of rats with cerebral ischemic brain injury possibly by affecting the expression of proteins involved in the TREK-1 signaling pathway.

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Activation of the TREK-1 Potassium Channel Improved Cognitive Deficits in a Mouse Model of Alzheimer’s Disease by Modulating Glutamate Metabolism

Zhou

Zeng

et al. 2022

Mol Neurobiol

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Arachidonic acid has protective effects on oxygen-glucose deprived astrocytes mediated through enhancement of potassium channel TREK-1 activity

Cited by 7 publications

References 25 publications

Activation of TREK-1 Potassium Channel Improved Cognitive Deficits in Alzheimer's Disease Model Mice by Modulation of Glutamate Metabolic Pathway

Activation of TREK-1 Potassium Channel Improved Cognitive Deficits in Alzheimer's Disease Model Mice by Modulation of Glutamate Metabolic Pathway

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

Activation of the TREK-1 Potassium Channel Improved Cognitive Deficits in a Mouse Model of Alzheimer’s Disease by Modulating Glutamate Metabolism

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