Involvement of TRPV4 channels in Aβ40-induced hippocampal cell death and astrocytic Ca2+ signalling

Bai, Ji‐Zhong; Lipski, Janusz

doi:10.1016/j.neuro.2014.01.001

Cited by 57 publications

(38 citation statements)

References 53 publications

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“…Additionally, in the central nervous system, TRPV4 is also expressed in the astrocytes and the endothelial cells and smooth muscle cells in cerebral arteries [1,2]. It has been reported that TRPV4-activity in astrocytes increases following ischemic insult and that activation of astrocytic TRPV4 is required for Aβ(40)-induced cell damage [9,33]. Over-activation of TRPV4 may result in oscillations in blood-vessel diameter [34], which may exacerbate the neuronal damage during cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Activation of Transient Receptor Potential Vanilloid 4 is Involved in Neuronal Injury in Middle Cerebral Artery Occlusion in Mice

Jie

Hong

et al. 2014

Mol Neurobiol

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Transient receptor potential vanilloid 4 (TRPV4) is widely expressed in the central nervous system and can be activated by multiple stimuli during cerebral ischemia. Recently, we reported that intracerebroventricular (icv.) injection of HC-067047, a specific TRPV4 antagonist, reduced brain infarction following 60-min of middle cerebral artery occlusion (MCAO). This study was undertaken to investigate the molecular mechanisms underlying TRPV4-mediated neuronal injury in cerebral ischemia. We demonstrated that TRPV4 expression was upregulated in the ipsilateral hippocampus at 4 to 48 h post-MCAO, peaking at 18 h post-MCAO. Treatment with TRPV4 antagonists (HC-067047 and ruthenium red) dose-dependently reduced brain infarction at 24 h post-MCAO. Phosphorylation of protein kinase B (p-Akt) was downregulated and that of extracellular signal-related kinase (p-ERK) was upregulated at 8 to 24 h post-MCAO, which was markedly blocked by treatment with HC-067047. Icv. injection of GSK1016790A (a TRPV4 agonist), dose-dependently induced hippocampal neuronal death, accompanied by an increase in phosphorylation of the NR2B subunit of the N-methyl-D-aspartate receptor (NMDAR). In addition, the level of p-Akt was decreased and that of p-ERK was increased by GSK1016790A-injection, which was sensitive to an NR2B antagonist. The neuronal toxicity of GSK1016790A was blocked by treatment with an NR2B antagonist and a phosphatidylinositol-3-kinase (PI3K) agonist but not by administration of a MAPK/ERK kinase antagonist. We conclude that the activation of TRPV4 is upregulated and involved in neuronal injury during cerebral ischemia and that the neurotoxicity associated with TRPV4-activation is mediated through NR2B-NMDAR and the related downregulation of the Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Activation of Transient Receptor Potential Vanilloid 4 is Involved in Neuronal Injury in Middle Cerebral Artery Occlusion in Mice

Jie

Hong

et al. 2014

Mol Neurobiol

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“…(). C , exposure of cultured astrocytes to Alzheimer's disease‐associated amyloid peptide Aβ 40 induces increased expression of astrocytic intermediate filament protein, GFAP, and TRPV4 ion channels; from Bai & Lipski ().…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic function of TRPV4 ion channels in the central nervous system

Kanju

Liedtke

2016

Experimental Physiology

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TRPV4 ion channels are osmo-mechano-TRP channels with pleiotropic function and expression in many different types of tissues and cells. They have also been found involved in pain and inflammation. Studies have focused on the role of TRPV4 in peripheral sensory neurons, but its expression and function in central nervous glial cells and neurons has also been documented. In this overview, based on the senior author’s lecture at the recent physiology meeting in Dublin, we concisely review evidence of TRPV4 expression and function in the CNS, and how TRPV4 function can be modulated for therapeutic benefit of neuro-psychiatric disorders. Novel TRPV4-inhibitory compounds developed recently in the authors’ lab will also be discussed

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“…The resultant cerebrovascular dysfunction may accelerate the AD pathogenesis by reducing the cerebral blood and glucose supply, increasing susceptibility to vascular insufficiency, and further promoting Aβ accumulation [59]. The other oxidative stress-sensitive TRP channels such as TRPV1, TRPV4, and TRPC1 are also implicated in Aβ-induced damages of other cell types including glia [60][61][62][63], smooth muscle cells [64], and ECs [65].…”

Section: Amyloid-βmentioning

confidence: 99%

“TRP inflammation” relationship in cardiovascular system

2015

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Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.

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Involvement of TRPV4 channels in Aβ40-induced hippocampal cell death and astrocytic Ca2+ signalling

Cited by 57 publications

References 53 publications

Activation of Transient Receptor Potential Vanilloid 4 is Involved in Neuronal Injury in Middle Cerebral Artery Occlusion in Mice

Activation of Transient Receptor Potential Vanilloid 4 is Involved in Neuronal Injury in Middle Cerebral Artery Occlusion in Mice

Pleiotropic function of TRPV4 ion channels in the central nervous system

“TRP inflammation” relationship in cardiovascular system

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