Expression and cellular distribution of transient receptor potential vanilloid 4 in cortical tubers of the tuberous sclerosis complex

Chen, Xin; Yang, Meihua; Sun, Fei-Ji; Liang, Chao; Wei, Yujia; Wang, Lukang; Yue, Jiong; Chen, Bing; Li, Song; Liu, Shiyong; Yang, Hui

doi:10.1016/j.brainres.2016.02.012

Cited by 13 publications

(9 citation statements)

References 32 publications

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“…TRPV4 is reportedly involved in epilepsy pathogenesis in patients and animal models. Increased TRPV4 expression has been reported in patients with intractable epilepsy caused by tuberous sclerosis complex and focal cortical dysplasia (X. Chen, Sun, et al, 2016; X. Chen, Yang, et al, 2016). We found that TRPV4 expression increased from 3 h to 30 d following PISE.…”

Section: Discussionmentioning

confidence: 99%

“…The present results further indicate that TRPV4 may play a dual role in the pathological process, especially in the early stage of epilepsy. It has been reported that TRPV4 may contribute to epilepsy pathogenesis (X. Chen, Sun, et al, 2016; X. Chen, Yang, et al, 2016; Men et al, 2019; Shibasaki et al, 2020; Wang et al, 2019), indicating that targeting TRPV4 is a promising therapeutic strategy. Combined with the previous reports, the utility of TRPV4 antagonists in the treatment of epilepsy would be cautious about the therapeutic dose and time window.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine‐induced status epilepticus in mice

Wang

et al. 2021

Journal Cellular Physiology

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The rapidly inactivating potassium current (I A ) is important in controlling neuronal action potentials. Altered I A function and K + channel expression have been found in epilepsy, and activation of the transient receptor potential vanilloid 4 (TRPV4) channel is involved in epilepsy pathogenesis. This study examined whether TRPV4 affects Kv4.2 and K + channel interacting protein (KCHIP) expression and I A changes following pilocarpine-induced status epilepticus (PISE) in mice. Herein, hippocampal protein levels of Kv4.2 and KCHIP2 increased 3 h-3 d and decreased 7-30 d; that of KCHIP1 increased 3-24 h and decreased 3-30 d post-PISE. The TRPV4 antagonist HC-067047 attenuated the increased protein levels of Kv4.2 and KCHIP2 but not that of KCHIP1 post-PISE. The TRPV4 agonist GSK1016790A increased hippocampal protein levels of Kv4.2 and KCHIP2 but had no effect on KCHIP1 expression. HC-067047 attenuated the increased I A in hippocampal pyramidal neurons 24 h and 3 d post-PISE. GSK1016790A increased I A in hippocampal pyramidal neurons, shifting the voltage-dependent inactivation curve toward depolarization. The GSK1016790A-induced increase of I A was blocked by protein kinase A and calcium/ calmodulin-dependent kinase II antagonists but was unaffected by protein kinase C antagonists. We conclude that TRPV4 activation may be responsible for the increases of Kv4.2 and KCHIP2 expression in hippocampi and I A in hippocampal pyramidal neurons in PISE mice, which are likely compensatory measures for hyperexcitability at the early stage of epilepsy.hippocampus, K + channel interacting protein, pilocarpine-induced status epilepticus rapidly inactivating potassium channel, transient receptor potential vanilloid 4

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine‐induced status epilepticus in mice

Wang

et al. 2021

Journal Cellular Physiology

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“…There is evidence that TRPV4 is likely involved in the pathogenesis of epilepsy. An increase in TRPV4 expression has been found in patients with the intractable epilepsy caused by tuberous sclerosis complex and focal cortical dysplasia (Chen, Sun, et al, 2016, Chen, Yang, et al, 2016). The expression of TRPV4 increased in TLE mice, and blockage of TRPV4 markedly blocked the changes in connexion 43 and neuronal death in TLE mice (Men et al., 2019; Wang et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

“…In recent studies, the involvement of TRPV4 in the pathogenesis of epilepsy has been reported (Men et al., 2019; Wang et al., 2019). TRPV4 was over‐expressed and is supposed to be linked with the intractable epilepsy caused by tuberous sclerosis complex (Chen, Yang, et al, 2016). Increased expression of TRPV4 was found in patients with focal cortical dysplasia that is a well‐known cause of medically intractable epilepsy (Chen, Sun, et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Transient receptor potential vanilloid 4 activation inhibits the delayed rectifier potassium channels in hippocampal pyramidal neurons: An implication in pathological changes following pilocarpine‐induced status epilepticus

Zhou

et al. 2020

J of Neuroscience Research

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Activation of transient receptor potential vanilloid 4 (TRPV4) can increase hippocampal neuronal excitability. TRPV4 has been reported to be involved in the pathogenesis of epilepsy. Voltage-gated potassium channels (VGPCs) play an important role in regulating neuronal excitability and abnormal VGPCs expression or function is related to epilepsy. Here, we examined the effect of TRPV4 activation on the delayed rectifier potassium current (I K) in hippocampal pyramidal neurons and on the Kv subunits expression in male mice. We also explored the role of TRPV4 in changes in Kv subunits expression in male mice following pilocarpine-induced status epilepticus (PISE). Application of TRPV4 agonists, GSK1016790A and 5,6-EET, markedly reduced I K in hippocampal pyramidal neurons and shifted the voltage-dependent inactivation curve to the hyperpolarizing direction. GSK1016790A-and 5,6-EET-induced inhibition of I K was blocked by TRPV4 specific antagonists, HC-067047 and RN1734. GSK1016790Ainduced inhibition of I K was markedly attenuated by calcium/calmodulin-dependent kinase II (CaMKII) antagonist. Application of GSK1016790A for up to 1 hr did not change the hippocampal protein levels of Kv1.1, Kv1.2, or Kv2.1. Intracerebroventricular injection of GSK1016790A for 3 d reduced the hippocampal protein levels of Kv1.2 and Kv2.1, leaving that of Kv1.1 unchanged. Kv1.2 and Kv2.1 protein levels as well as I K reduced markedly in hippocampi on day 3 post PISE, which was significantly reversed by HC-067047. We conclude that activation of TRPV4 inhibits I K in hippocampal pyramidal neurons, possibly by activating CaMKII. TRPV4-induced decrease in Kv1.2 and Kv2.1 expression and I K may be involved in the pathological changes following PISE.

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“…Tuberous sclerosis and cortical dysplasia are often accompanied by refractory epilepsy. The expression of TRPV4 is markedly increased in cortical nodules or the dysplastic cortex of these patients and is signi cantly correlated with seizure symptoms (Chen et al 2016a, b). In mice, high-temperature stimulation can promote epileptic seizures by activating TRPV4 (Shibasaki et al 2020), while in zebra sh low-temperature treatment can inhibit epileptic discharges in the forebrain by inhibiting TRPV4 (Hunt et al 2012).…”

Section: Introductionmentioning

confidence: 99%

The Nuclear Factor-Kappa B Signaling Pathway is Involved in Transient Receptor Potential Vanilloid 4-Mediated Inflammatory Responses and Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus

et al. 2021

Preprint

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The blockage of transient receptor potential vanilloid 4 (TRPV4) greatly reduces hippocampal neuronal injury in mice with temporal lobe epilepsy through inhibiting inflammation. NF-κB signaling pathway is activated during epilepsy, leading to enhanced inflammation and neuronal injury. Here, we explored whether TRPV4 blockage could affect the NF-κB pathway in mice with pilocarpine-induced status epilepticus (PISE). Application of a TRPV4 antagonist markedly attenuated the PISE-induced increase in hippocampal HMGB1, TLR4, phospho (p)-IκK (p-IκK), and p-IκBα protein levels, as well as those of cytoplasmic p-NF-κB p65 (p-p65) and nuclear NF-κB p65 and p50; in contrast, the application of GSK1016790A, a TRPV4 agonist, showed similar changes to PISE mice. Administration of the TLR4 antagonist TAK-242 or the NF-κB pathway inhibitor BAY 11-7082 led to a noticeable reduction in the hippocampal protein levels of cleaved IL-1β, IL-6 and TNF, as well as those of cytoplasmic p-p65 and nuclear p65 and p50 in GSK1016790A-injected mice. Finally, administration of either TAK-242 or BAY 11-7082 greatly increased neuronal survival in hippocampal CA1 and CA2/3 regions in GSK1016790A-injected mice. We conclude that TRPV4 activation increases HMGB1 and TLR4 expression, leading to IκK and IκBα phosphorylation and, consequently, NF-κB activation and nuclear translocation. The resulting increase in pro-inflammatory cytokine production is responsible for TRPV4 activation-induced neuronal injury. Meanwhile, blocking TRPV4 can downregulate HMGB1/TLR4/IκK/κBα/NF-κB signaling following PISE onset, an effect that may underlie the neuroprotective ability of TRPV4 blockage in mice with PISE.

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Expression and cellular distribution of transient receptor potential vanilloid 4 in cortical tubers of the tuberous sclerosis complex

Cited by 13 publications

References 32 publications

Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine‐induced status epilepticus in mice

Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine‐induced status epilepticus in mice

Transient receptor potential vanilloid 4 activation inhibits the delayed rectifier potassium channels in hippocampal pyramidal neurons: An implication in pathological changes following pilocarpine‐induced status epilepticus

The Nuclear Factor-Kappa B Signaling Pathway is Involved in Transient Receptor Potential Vanilloid 4-Mediated Inflammatory Responses and Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus

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