scholarly journals Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol, and mustard oil

2018 ◽  
Author(s):  
Sara C.M. Leijon ◽  
Amanda F. Neves ◽  
Joseph M. Breza ◽  
Sidney A. Simon ◽  
Nirupa Chaudhari ◽  
...  
Keyword(s):  
Allyl Isothiocyanate ◽  
Mustard Oil ◽  
Oral Stimulation ◽  
Trigeminal Neurons ◽  
Oral Sensory ◽  
Thermal Sensing ◽  
Confocal Calcium Imaging ◽  
Ganglion Neurons ◽  
Chili Peppers

When consumed with foods, mint, mustard and chili peppers generate pronounced oral thermosensations. Here we recorded responses in mouse trigeminal ganglion neurons to investigate interactions between thermal sensing and the active ingredients of these plants--menthol, allyl isothiocyanate (AITC), and capsaicin, respectively--at concentrations found in foods and commercial hygiene products. We carried out in vivo confocal calcium imaging of trigeminal ganglia in which neurons express GCaMP3 or GCAMP6s and recorded their responses to oral stimulation with thermal and the above chemesthetic stimuli. In the V3 (oral sensory) region of the ganglion, thermoreceptive neurons accounted for ~10% of imaged neurons. We categorized them into 3 distinct classes: cool-responsive and warm-responsive thermosensors, and nociceptors (responsive only to temperatures ≥43-45o). Menthol, AITC, and capsaicin also elicited robust calcium responses that differed markedly in their latencies and durations. Most of the neurons that responded to these chemesthetic stimuli were also thermosensitive. Capsaicin and AITC increased the numbers of warm-responding neurons and shifted the nociceptor threshold to lower temperatures. Menthol attenuated the responses in all classes of thermoreceptors. Our data show that while individual neurons may respond to a narrow temperature range (or even bimodally), taken collectively, the population is able to report on graded changes of temperature. Our findings also substantiate an explanation for the thermal sensations experienced when one consumes pungent spices or mint.

scholarly journals POU domain factor Brn-3a controls the differentiation and survival of trigeminal neurons by regulating Trk receptor expression

Development ◽  
1999 ◽  
Vol 126 (13) ◽  
pp. 2869-2882 ◽  
Author(s):  
E.J. Huang ◽  
K. Zang ◽  
A. Schmidt ◽  
A. Saulys ◽  
M. Xiang ◽  
...  
Keyword(s):  
Receptor Expression ◽  
Neurotrophin Receptor ◽  
Trk Receptors ◽  
Pou Domain ◽  
Trk Receptor ◽  
Regulatory Circuit ◽  
Trigeminal Neurons ◽  
Initial Generation ◽  
Ganglion Neurons

Mice lacking the POU domain-containing transcription factor Brn-3a have several neuronal deficits. In the present paper, we show that Brn-3a plays two distinct roles during development of the trigeminal ganglion. In this ganglion, neurons expressing the neurotrophin receptors, TrkB and TrkC, are born between E9.5 and E11.5. In the absence of Brn-3a, very few neurons ever express TrkC, but TrkB-expressing neurons are present at E12.5 in elevated numbers, suggesting that Brn-3a may be a constituent of a regulatory circuit determining which Trk receptor is expressed by these early-born neurons. Most neurons expressing the neurotrophin receptor TrkA are generated between E11.5 and E13.5 in this ganglion and their initial generation is not prevented by absence of Brn-3a. However, after E12. 5, absence of Brn-3a results in a progressive loss in neuronal TrkA and TrkB expression, which leads to a massive wave of apoptosis that peaks at E15.5. Despite complete absence of the Trk receptors at E17. 5 and P0, approximately 30% of the normal complement of neurons survive to birth in Brn-3a mutants. Approximately 70% of these express the GDNF receptor subunit, c-ret; many can be sustained by GDNF, but not by NGF in culture. Thus, the vast majority of surviving neurons are probably sustained in vivo by trophic factor(s) whose receptors are not regulated by Brn-3a. In conclusion, our data indicate the specific functions of Brn-3a in controlling the survival and differentiation of trigeminal neurons by regulating expression of each of the three Trk receptors.

Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4173-4178 ◽  
Author(s):  
L.G. Pinon ◽  
G. Middleton ◽  
A.M. Davies
Keyword(s):  
Embryonic Development ◽  
Sensory Neurons ◽  
Neuronal Death ◽  
Null Mouse ◽  
Wild Type ◽  
Naturally Occurring ◽  
Age Related ◽  
Trigeminal Neurons ◽  
Ganglion Neurons

To ascertain the role of endogenous Bcl-2 in maintaining the survival of developing neurons and modulating their responses to neurotrophins, we compared the in vitro and in vivo survival of cranial sensory neurons of wild-type and bcl-2 null mouse embryos. At the peak of naturally occurring neuronal death in the trigeminal ganglion at E14, trigeminal neurons from bcl-2(−/−) embryos initially survived in culture in response to NGF but were not sustained as well as neurons from wild-type embryos. At the end of the period of naturally occurring neuronal death at E18, Bcl-2-deficient trigeminal neurons survived with NGF as well as wild-type neurons. At E14 in vivo, the number of trigeminal neurons undergoing apoptosis was significantly greater in bcl-2(−/−) embryos, and there were significantly fewer neurons in the trigeminal ganglia of bcl-2(−/−) embryos at E16 and E18. Similar age-related changes in the responses of nodose ganglion neurons to BDNF were observed in cultures established from bcl-2(−/−) and wild-type embryos between E14 and E18. These results suggest that endogenous Bcl-2 is required for the sustained survival response of a subset of cranial sensory neurons to neurotrophins at particular stages of embryonic development and show that its absence leads to reduced numbers of these neurons in vivo.

scholarly journals Petasin and isopetasin reduce CGRP release from trigeminal afferents indicating an inhibitory effect on TRPA1 and TRPV1 receptor channels

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Johanna Kleeberg-Hartmann ◽  
Birgit Vogler ◽  
Karl Messlinger
Keyword(s):  
Inhibitory Effect ◽  
Transient Receptor Potential Channels ◽  
Mustard Oil ◽  
Root Extract ◽  
Dependent Manner ◽  
Trpv1 Receptor ◽  
Cgrp Release ◽  
Ganglion Neurons ◽  
Sites Of Action ◽  
The Impact

Abstract Background Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Methods We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay. Results Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels. Conclusions Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.

scholarly journals Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192760
Author(s):  
Jason A. Bleedorn ◽  
Troy A. Hornberger ◽  
Craig A. Goodman ◽  
Zhengling Hao ◽  
Susannah J. Sample ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Signaling Events ◽  
Bone Loading ◽  
Ganglion Neurons

Regulation of expression of mRNAs encoding the nerve growth factor receptors p75 and trkA in developing sensory neurons

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 635-648 ◽  
Author(s):  
S. Wyatt ◽  
A.M. Davies
Keyword(s):  
Neuronal Development ◽  
Polymerase Chain Reaction Amplification ◽  
Mrna Levels ◽  
Regulation Of Expression ◽  
Trigeminal Neurons ◽  
Nerve Growth Factor Receptors ◽  
Reaction Amplification ◽  
Amplification Technique

We have used a quantitative reverse transcription/polymerase chain reaction amplification technique to study the regulation of p75 mRNA and trkA mRNA expression in developing NGF-dependent trigeminal neurons. Before becoming NGF dependent, these neurons express low levels of p75 and trkA mRNAs in vivo. At this stage in vitro, the level of p75 mRNA is maintained and up-regulated by BDNF, whereas the level of trkA mRNA is sustained independently of neurotrophins and is down-regulated by BDNF. With the acquisition of NGF dependence, p75 and trkA mRNA levels increase markedly in vivo. At this stage in vitro, the level of p75 mRNA is up-regulated by NGF, but this response is lost at later stages. The level of trkA mRNA is sustained in neurons grown with NGF but is not up-regulated by concentrations of NGF above those required to support survival. At no stage during the early development of trigeminal neurons do depolarising levels of potassium ions affect the expression of either p75 mRNA or trkA mRNA. These findings suggest that the expression of p75 and trkA mRNAs are differentially regulated by BDNF and NGF at successive early stages of neuronal development.

GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development

Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3773-3782 ◽  
Author(s):  
Eri Hashino ◽  
Marlene Shero ◽  
Dirk Junghans ◽  
Hermann Rohrer ◽  
Jeffrey Milbrandt ◽  
...  
Keyword(s):  
Striate Muscle ◽  
Ciliary Ganglion ◽  
Neuron Development ◽  
Down Regulation ◽  
Eye Muscle ◽  
Ciliary Ganglion Neurons ◽  
Ganglion Neurons ◽  
Parasympathetic Neuron

During development, parasympathetic ciliary ganglion neurons arise from the neural crest and establish synaptic contacts on smooth and striate muscle in the eye. The factors that promote the ciliary ganglion pioneer axons to grow toward their targets have yet to be determined. Here, we show that glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN) constitute target-derived factors for developing ciliary ganglion neurons. Both GDNF and NRTN are secreted from eye muscle located in the target and trajectory pathway of ciliary ganglion pioneer axons during the period of target innervation. After this period, however, the synthesis of GDNF declines markedly, while that of NRTN is maintained throughout the cell death period. Furthermore, both in vitro and in vivo function-blocking of GDNF at early embryonic ages almost entirely suppresses ciliary axon outgrowth. These results demonstrate that target-derived GDNF is necessary for ciliary ganglion neurons to innervate ciliary muscle in the eye. Since the down-regulation of GDNF in the eye is accompanied by down-regulation of GFRα1 and Ret, but not of GFRα2, in innervating ciliary ganglion neurons, the results also suggest that target-derived GDNF regulates the expression of its high-affinity coreceptors.

Activity of in vivo canine cardiac plexus neurons

1988 ◽  
Vol 255 (4) ◽  
pp. H789-H800 ◽  
Author(s):  
M. Gagliardi ◽  
W. C. Randall ◽  
D. Bieger ◽  
R. D. Wurster ◽  
D. A. Hopkins ◽  
...  
Keyword(s):  
Cardiac Cycle ◽  
Pulmonary Veins ◽  
Systolic Pressure ◽  
Identified Neurons ◽  
Fat Pad ◽  
Respiratory Dynamics ◽  
The Right ◽  
Ganglion Neurons ◽  
Ganglionated Plexus

The activity of 394 spontaneously active neurons located in the ganglionated plexus of the ventral epicardial fat pad overlying the right atrium and pulmonary veins was recorded. Ganglia that contained various numbers of neurons, many with two or more nucleoli, were identified adjacent to the recording sites. Spontaneous activity was correlated with the cardiac cycle in 39% and with the respiratory cycle in 8% of the identified neurons. Neuronal activity occurred in specific phases of the cardiac cycle when arterial pressure was between approximately 70 and 175 mmHg. During increases in systolic pressure induced by positive inotropic agents or aortic occlusion, responses of neurons that displayed cardiovascular-related activity were enhanced. These responses persisted after acute decentralization. The activity of 14% of all identified neurons was altered when discrete regions of the heart, great thoracic vessels, or lungs were mechanically distorted by gentle touch. Trains of stimuli, but not single stimuli, delivered to the vagosympathetic complexes, stellate ganglia, or cardiopulmonary nerves activated ganglionic neurons in intact or acutely decentralized preparations. It is concluded that the activity of some cardiac ganglion neurons is related to cardiovascular or respiratory dynamics and that some of these neurons receive inputs from sympathetic and parasympathetic efferent axons as well as from cardiac mechanoreceptors.

scholarly journals TRPV1-lineage somatosensory fibers communicate with taste neurons in the mouse parabrachial nucleus

2021 ◽  
Author(s):  
Jinrong Li ◽  
Md Sams Sazzad Ali ◽  
Christian H Lemon
Keyword(s):  
Oral Delivery ◽  
Optical Excitation ◽  
Cell Types ◽  
Parabrachial Nucleus ◽  
Somatosensory Processing ◽  
Noxious Heat ◽  
Trigeminal Neurons ◽  
Taste Cells ◽  
Thermal Stimuli

Trigeminal neurons supply somatosensation to craniofacial tissues. In mouse brain, ascending projections from medullary trigeminal neurons arrive at taste neurons in the autonomic parabrachial nucleus, suggesting taste neurons participate in somatosensory processing. However, the genetic cell types that support this convergence were undefined. Using Cre-directed optogenetics and in vivo neurophysiology in anesthetized mice of both sexes, here we studied whether TRPV1-lineage nociceptive and thermosensory fibers are primary neurons that drive trigeminal circuits reaching parabrachial taste cells. We monitored spiking activity in individual parabrachial neurons during photoexcitation of the terminals of TRPV1-lineage fibers that arrived at the dorsal spinal trigeminal nucleus pars caudalis, which relays orofacial somatosensory messages to the parabrachial area. Parabrachial neural responses to oral delivery of taste, chemesthetic, and thermal stimuli were also recorded. We found that optical excitation of TRPV1-lineage fibers frequently stimulated traditionally defined taste neurons in lateral parabrachial nuclei. The tuning of neurons across diverse tastes associated with their sensitivity to excitation of TRPV1-lineage fibers, which only sparingly engaged neurons oriented to preferred tastes like sucrose. Moreover, neurons that responded to photostimulation of TRPV1-lineage afferents showed strong responses to temperature including noxious heat, which predominantly excited parabrachial bitter taste cells. Multivariate analyses revealed the parabrachial confluence of TRPV1-lineage signals with taste captured sensory valence information shared across aversive gustatory, nociceptive, and thermal stimuli. Our results reveal that trigeminal fibers with defined roles in thermosensation and pain communicate with parabrachial taste neurons. This multisensory convergence supports dependencies between gustatory and somatosensory hedonic representations in the brain.

A nano-phytochemical ophthalmic solution for marked improvement of corneal wound healing in healthy or diabetic mice

Nanomedicine ◽  
2021 ◽  
Author(s):  
Qiqi Li ◽  
Meng Xin ◽  
Xianggen Wu ◽  
Bo Lei
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Diabetic Mice ◽  
Promoting Effect ◽  
Related Factors ◽  
Corneal Wound Healing ◽  
Corneal Epithelial ◽  
Trigeminal Neurons ◽  
Corneal Wound

Aim: To formulate a novel nano-phytochemical ophthalmic solution to promote corneal wound healing. Methods: Dipotassium glycyrrhizinate (DG) and palmatine (PAL) were used to formulate this formulation marked as DG-PAL, and its efficacy and mechanisms for promoting corneal wound healing were evaluated in mice. Results: DG-PAL was easily fabricated with excellent physical profiles. In in vivo efficiency evaluations, DG-PAL demonstrated an excellent promoting effect on corneal epithelial/nerve wound healing in both healthy and diabetic mice. These effects were involved in the DG-PAL-induced decreased expression levels of HMGB1 and its signaling-related factors in the corneas and trigeminal neurons of the healthy or diabetic mice. Conclusion: DG-PAL possibly represents a promising ophthalmic solution for promoting corneal wound healing.

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