TRPV1 Regulates Stress Responses through HDAC2

Wang, Sung Eun; Ko, Seung Yeon; Jo, Sungsin; Choi, Mark; Lee, Jun Young; Jo, Hye Ryeong; Seo, Jee Young; Lee, Sang Hoon; Kim, Yong Seok; Jung, Sung Jun; Son, Hyeon

doi:10.1016/j.celrep.2017.03.050

Cited by 47 publications

(53 citation statements)

References 45 publications

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“…There are a number of reports of the functional roles of HDAC2 in the maturation of neural cells, 26 , 27 especially in neurogenesis 28 and synaptic plasticity. 17 According to our recent work, 7 TRPV1 loss of function induces downregulation of HDAC2 in the DG, leading to elevated expression of neurogenesis- and synaptic plasticity-related genes, which contributes to stress-resilient behavior. However, increase of HDAC2 expression in the DG induces depression-like behaviors, which were blocked by HDAC2 knockdown.…”

Section: Discussionmentioning

confidence: 99%

“…TRPV1 activation by systemic injection of agonists such as capsaicin and resiniferatoxin elicits anxiogenic responses and depression-related behaviors, whereas its antagonists induce anxiolytic- and antidepressant-like effects in rodents. 4 , 5 , 6 , 7 Besides, direct injection of capsaicin or capsazepine in the hippocampus induces anxiety- or anxiolytic-like effects. 8 , 9 These effects are accompanied by impaired hippocampal neurogenesis through epigenetic regulation.…”

Section: Introductionmentioning

confidence: 99%

“… 12 We recently demonstrated that the antidepressant-like effects induced by TRPV1 deficiency are associated with HDAC2 downregulation. 7 However, TRPV1 activation produces depression-like effects with an increase in HDAC2 expression. However, there is no evidence that TRPV1 activation by agonists induces HDAC2 upregulation and thereby alters synaptic molecules or neuronal maturation in the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

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Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice

Wang

Kim

et al. 2018

Exp Mol Med

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Transient receptor potential vanilloid 1 (TRPV1) affects mood and neuroplasticity in the brain, where its role is poorly understood. In the present study we investigated whether capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide), an agonist of TRPV1, induced chromatin remodeling and thereby altered gene expression related to synaptic plasticity. We found that capsaicin treatment resulted in upregulation of histone deacetylase 2 (HDAC2) in the mouse hippocampus and HDAC2 was enriched at Psd95, synaptophysin, GLUR1, GLUR2 promoters. Viral-mediated hippocampal knockdown of HDAC2 induced expression of Synapsin I and prevented the detrimental effects of capsaicin on Synapsin I expression in mice, supporting the role of HDAC2 in regulation of capsaicin-induced Synapsin I expression. Taken together, our findings implicate HDAC2 in capsaicin-induced transcriptional regulation of synaptic molecules and support the view that HDAC2 is a molecular link between TRPV1 activity and synaptic plasticity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice

Wang

Kim

et al. 2018

Exp Mol Med

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“…Following single injections of various doses of metformin, the anti-depressant effect was indicated by the responses in the forced swimming test (FST) and tail suspension test (TST), two widely used behavioral tests of depression. The FST focuses immobility time after mice being placed in a tank filled with water from which animals cannot escape, while the TST has a common theoretical basis and behavioral measure with the FST but avoids motor dysfunction that may interfere with evaluation in a FST [36,37]. In the group that received metformin > 10 mg/kg, the immobility time in the FST and TST was significantly decreased compared to that in the vehicle-injected or 10 mg/kg metformin-injected groups (F (4, 35) = 6.226, P < 0.001 for FST; F (4, 35) = 9.961, P < 0.001 for TST; Fig.…”

Section: Metformin Exerts Antidepressant Effects On Mice In a Dose-anmentioning

confidence: 99%

Antidiabetic Drug Metformin Ameliorates Depressive-Like Behavior in Mice with Chronic Restraint Stress via Activation of AMP-Activated Protein Kinase

Ai¹,

Fang²,

Hu³

et al. 2020

Aging and disease

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Depression is one of the most prevalent neuropsychiatric disorders in modern society. However, traditional drugs, such as monoaminergic agents, have defect showing lag response requiring several weeks to months. Additionally, these drugs have limited efficacy and high resistance rates in patients with depression. Thus, there is an urgent need to develop novel drugs or approaches for the treatment of depression. Here, using biochemical, pharmacological, genetic and behavioral methods, we demonstrate that metformin imparts a fastacting antidepressant-like effect in naï ve mice as well as stressed mice subjected to chronic restraint stress model. Moreover, inhibition of AMP-activated protein kinase (AMPK) activity by compound C or knock down of hippocampal AMPKα occluded the antidepressant-like effect induced by metformin. Our results suggest that metformin may be a viable therapeutic drug for the treatment of stress-induced depression via activation of AMPK.

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“…TRPV1 channel belongs to the Ca 2+ permeable TRPV channel family, responding to noxious heat (>43℃), low pH value (<5), capsaicin and so on [10][11][12]. TRPV1 channel plays an important role in several physiological and pathological processes, such as nerve conduction, visceral pain sensing process [9,13,14], and activation of immunity [15]. Furthermore, a few studies shown previously that TRPV1 was likely involved in tumor progression [16], and its activation reduced cell proliferation, migration and invasion in breast cancer [17], urothelial cancer [18] and papillary thyroid carcinoma [19].…”

Section: Introductionmentioning

confidence: 99%

A Unique Role Of TRPV1 Ion Channels In The Suppression Of Gastric Cancer Development

Gao

Feng

Chen

et al. 2020

Preprint

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Background: Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association of transient receptor potential vanilloid receptor 1(TRPV1) channels and gastric cancer (GC) has not been explored so far. We sought to determine their role in the development of GC and to elucidate the underlying molecular mechanisms. Methods: The expression of TRPV1 in GC cells and tissues was detected by qPCR, immunohistochemistry, western blot analysis and immunofluorescence. CCK8 and flow cytometry were used to detect the proliferation and cell cycle, while transwell assay was used to detect migration and invasion. The role of TRPV1 in GC development in vivo was tested using tumor xenograft and peritoneal dissemination assays in nude mice. Results: The decreased expression of TRPV1 protein in primary human GC tissues was closely correlated with poor prognosis of GC patients. TRPV1 protein was predominately expressed on the plasma membrane of several GC cell lines. TRPV1 overexpression attenuated proliferation, migration and invasion of GC cells in vitro, but TRPV1 knockdown increased them. Moreover, TRPV1 significantly reduced gastric tumor sizes, numbers and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, but TRPV1 knockdown caused the opposite effects.Conclusions: TRPV1 uniquely suppresses GC through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival in human GC. TRPV1 upregulation and its downstream signaling may be a promising strategy for GC prevention and therapy.

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TRPV1 Regulates Stress Responses through HDAC2

Cited by 47 publications

References 45 publications

Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice

Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice

Antidiabetic Drug Metformin Ameliorates Depressive-Like Behavior in Mice with Chronic Restraint Stress via Activation of AMP-Activated Protein Kinase

A Unique Role Of TRPV1 Ion Channels In The Suppression Of Gastric Cancer Development

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