OBJECTIVE: Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN. METHODS: Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4^-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN. RESULTS: The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4^-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure. CONCLUSION TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.
Animals ; Mice ; TRPV Cation Channels/metabolism* ; Intermediate Filaments/metabolism* ; Hippocampus/metabolism* ; Neurons/metabolism* ; Memory Disorders/metabolism*

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
Animals ; Astrocytes/metabolism* ; Complement C3/metabolism* ; Epilepsy ; Mice ; Neurons/pathology* ; Status Epilepticus ; TRPV Cation Channels/metabolism*

PURPOSE: Pain from vertebral or femoral neck fractures is a particularly important problem in clinical orthopaedics. Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, and there are recent reports on an association between bone pain and TRPV1. However, an increase in TRPV1 activity has not been reported following femoral fracture. MATERIALS AND METHODS: We applied a neurotracer [Fluoro-gold (FG)] onto femur to detect dorsal root ganglia (DRGs) innervating the cortex of the femur in 30 Sprague Dawley rats. Seven days after application, a closed mid-diaphyseal fracture of the femur was performed. FG labeled TRPV1-immunoreactive (ir) DRGs innervating the femur were examined in nonfractured controls, and 3 days, 1 week, 2 weeks, and 4 weeks after fracture. We evaluated bone healing of the femur and compared the ratio of TRPV1-ir DRG neurons innervating the femur at the time points. RESULTS: Four weeks after fracture, complete bone union was observed. There was no significant difference in the ratio of FG labeled DRG neurons to total DRG neurons at each time point. The percentages of TRPV1-ir neurons in DRGs innervating the femur at 3 days and 1 week after fracture were significantly higher than those in control, 2 weeks, and 4 weeks after fracture (p<0.05). CONCLUSION: Fracture induced an increase of TRPV1-ir neurons in DRGs innervating the fractured femur within 3 days, and decreased during bone healing over 4 weeks. These findings show that TRPV1 may play a role in sensory sensation of bone fracture pain.
Animals ; Female ; Femur/*innervation/*metabolism ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/*metabolism

The transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues where it participates in the generation of Ca2+ signals and/or depolarization of the membrane potential. Regulation of TRPV4 abundance at the cell surface is critical for osmo- and mechanotransduction. Defects in TRPV4 are the cause of several human diseases, including brachyolmia type 3 (MIM:113500) (also known as brachyrachia or spondylometaphyseal dysplasia Kozlowski type [MIM:118452]), and metatropic dysplasia (MIM:156530) (also called metatropic dwarfism or parastremmatic dwarfism [MIM:168400]). These bone dysplasia mutants are characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. These diseases are characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly, and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses, and apophyses. In this review, we discuss the potential effect of the mutation on the regulation of TRPV4 functions, which are related to human diseases through deviated function. In particular, we emphasize how the constitutive active TRPV4 mutant affects endochondral ossification with a reduced number of hypertrophic chondrocytes and the presence of cartilage islands within the zone of primary mineralization. In addition, we summarize current knowledge about the role of TRPV4 in the pathogenesis of several diseases.
Humans ; *Mutation ; Osteochondrodysplasias/*genetics ; Osteogenesis/genetics ; TRPV Cation Channels/chemistry/*genetics/metabolism

The five-flavor theory of traditional Chinese medicines (TCM) and the flavor efficacy generation mechanism has long been focuses and difficulties in studies on traditional Chinese medicinal properties. In this paper, by using the pharmacophore-based virtual screening technique, the authors discussed the relations between the pungent property and transient receptor potential vanilloid 1 (TRPV1) by studying the TCM components' role in regulating TRPV1 ion channel. The results showed that the matching relationship between TRPV1 agonist pharmacophore model and TCM chemical components could identify the active ingredients from pungent herbs. Therefore, the authors proposed that TRPV1 is one of the potential targets for efficient pungent herbs. The pungent property of TCMs is decided by its chemical components, and consistent with the inherited and additive characteristics.
Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Smell ; TRPV Cation Channels ; antagonists & inhibitors ; metabolism ; Taste

Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge: capsaicin binds to a pocket formed by the channel's transmembrane segments, where it takes a "tail-up, head-down" configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by "pull-and-contact" with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1.
Binding Sites ; Capsaicin ; chemistry ; pharmacokinetics ; Humans ; Hydrogen Bonding ; Protein Binding ; TRPV Cation Channels ; chemistry ; genetics ; metabolism

OBJECTIVETo investigate the expression of transient receptor potential melastatin (TRPM) and transient receptor potential vanilloid (TRPV) channel family genes in rat spermatogenic cells.

METHODSRat spermatogenic cells were isolated by a mechanical procedure and the total RNA was extracted using TRIzol reagent. TRPM and TRPV channel family genes were amplified by RT-PCR and the presence of the target genes was detected by agarose gel electrophoresis. The relative gene expression levels were measured by real-time quantitative RT-PCR.

RESULTSTRPV5, TRPM3, TRPM4 and TRPM7 mRNAs were expressed in rat spermatogenic cells, but TRPV1, TRPV2, TRPV3, TRPV4, TRPV6, TRPM1, TRPM2, TRPM5, TRPM6, TRPM7 and TRPM8 mRNAs were not detected. The relative expressions of TRPM and TRPV mRNA were determined by quantitative real-time RT-PCR. TRPM7 expression was the highest among all the TRPM subtypes in rat spermatogenic cells, at a level equivalent to (0.0430-/+0.0034)% of beta-actin expression. TRPM3 and TRPM4 were also highly expressed, but their expression levels were only approximately 56% and 63% of that of TRPM7, respectively. For the TRPV subfamily, only TRPV5 mRNA was abundantly expressed at the level of (0.0157-/+0.0029)% relative to that of beta-actin.

CONCLUSIONTRPV5, TRPM3, TRPM4 and TRPM7 mRNAs were coexpressed in spermatogenic cells in rats, among which TRPM4 and TRPM7 mRNA were expressed at high levels. TRPM4 and TRPM7 channels may be involved in the regulation of growth, differentiation and maturation of rat spermatogenic cells and are associated with the generation of the sperms.

Animals ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spermatocytes ; cytology ; metabolism ; Spermatogonia ; cytology ; metabolism ; TRPM Cation Channels ; genetics ; metabolism ; TRPV Cation Channels ; genetics ; metabolism

OBJECTIVETo study the expression of the mRNAs of transient receptor potential (TRP) gene subfamily TRPV and TRPM in rat testes.

METHODSNormal SD rat testes were collected and the expression of TRPV and TRPM mRNAs were detected by routine RT-PCR.

RESULTSThe TRPV4, TRPV5, TRPV6, TRPM3, TRPM4 and TRPM8 mRNAs were detected in the rat testes, but the other members of TRPV and TRPM family were not detected.

CONCLUSIONSTRPV4, TRPV5, TRPV6, TRPM3, TRPM4 and TRPM8 are expressed in rat testes. This finding provides the basis for exploring the functions of TRPV and TRPM in the testes and the relation between testis diseases and the TRP family.

Animals ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; TRPM Cation Channels ; genetics ; metabolism ; TRPV Cation Channels ; genetics ; metabolism ; Testis ; metabolism

OBJECTIVETo study the effects of the ingredients from Chinese herbs with the nature of cold or hot on the expression of TRPV1 and TRPM8.

METHODThe effects of ingredients from herbs on primary culture DRG neurons are observed in vitro. The expression quantity of gene is detected by the method of real time PCR. the 2 (-deltadeltaCT) method is applied to analyze the data.

RESULTIngredients from herbs with the nature of cold up-regulate the expression level of TRPV1 and down-regulate that of TRPM8, especially under the temperature condition of 39 degrees C; while ingredients from herbs with the nature of hot up-regulate the expression level of TRPM8 and down-regulated that of TRPV1, which is more significant under the temperature condition of 19 degrees C.

CONCLUSIONThe regulatory changes of TRPV1 and TRPM8 mRNA expression induced by the chemical ingredients might be related to the cold and hot natures of the herbs from which the ingredients are extracted. And this could be one of the therapeutic mechanisms for the treatment of Chinese herbal medicines to cold- and heat-related diseases.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; Gene Expression ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; TRPM Cation Channels ; genetics ; metabolism ; TRPV Cation Channels ; genetics ; metabolism

OBJECTIVETo study the possible mechanisms of chronic nonbacterial prostatitis (CNP) pain.

METHODSCNP models were established in male Wistar rats by the autoimmune method. Then the paw withdrawal threshold (PWT) was detected using the Von Frey filament, prostate pathological examination was conducted, the expressions of substance P (SP) and transient receptor potential vanilloid 1 (TRPV1) in the prostate tissue and L5-S2 spinal segments were determined by immunohistochemistry and their correlations were analyzed.

RESULTSCompared with the control group, the CNP model rats showed markedly decreased PWT (P < 0.05) and obvious inflammation in the prostate tissue, with significant differences in the scope of lesion and interstitial lymphocyte infiltration (P < 0.05). The expressions of SP and TRPV1 in the prostate and spinal cord dorsal horn L5-S2 were remarkably upregulated in the models as compared with the control rats (P < 0.05). However, the expression of SP in the prostate was not correlated with that in the spinal cord (r = 0.099, P = 0.338), nor was that of TRPV1 (r = 0.000, P = 0.5).

CONCLUSIONSP and TRPV1 were involved in the formation and persistence of pain in CNP rats through their upregulated expressions in the L5-S2 spinal segments.

Animals ; Lumbosacral Region ; Male ; Neuralgia ; metabolism ; physiopathology ; Pain ; metabolism ; physiopathology ; Prostate ; metabolism ; Prostatitis ; metabolism ; physiopathology ; Rats ; Rats, Wistar ; Spinal Cord ; metabolism ; Substance P ; metabolism ; TRPV Cation Channels ; metabolism