scholarly journals Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons

2019 ◽  
Vol 116 (9) ◽  
pp. 3811-3816 ◽  
Author(s):  
A. P. Luiz ◽  
D. I. MacDonald ◽  
S. Santana-Varela ◽  
Q. Millet ◽  
S. Sikandar ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Transcriptional Profiling ◽  
Relative Number ◽  
Trp Channel ◽  
Maximal Response ◽  
Cold Plate ◽  
Cold Temperatures ◽  
Extreme Cold ◽  
Cold Sensing

The ability to detect environmental cold serves as an important survival tool. The sodium channels NaV1.8 and NaV1.9, as well as the TRP channel Trpm8, have been shown to contribute to cold sensation in mice. Surprisingly, transcriptional profiling shows that NaV1.8/NaV1.9 and Trpm8 are expressed in nonoverlapping neuronal populations. Here we have used in vivo GCaMP3 imaging to identify cold-sensing populations of sensory neurons in live mice. We find that ∼80% of neurons responsive to cold down to 1 °C do not express NaV1.8, and that the genetic deletion of NaV1.8 does not affect the relative number, distribution, or maximal response of cold-sensitive neurons. Furthermore, the deletion of NaV1.8 had no observable effect on transient cold-induced (≥5 °C) behaviors in mice, as measured by the cold-plantar, cold-plate (5 and 10 °C), or acetone tests. In contrast, nocifensive-like behavior to extreme cold-plate stimulation (−5 °C) was completely absent in mice lacking NaV1.8. Fluorescence-activated cell sorting (FACS) and subsequent microarray analysis of sensory neurons activated at 4 °C identified an enriched repertoire of ion channels, which include the Trp channel Trpm8 and potassium channel Kcnk9, that are potentially required for cold sensing above freezing temperatures in mouse DRG neurons. These data demonstrate the complexity of cold-sensing mechanisms in mouse sensory neurons, revealing a principal role for NaV1.8-negative neurons in sensing both innocuous and acute noxious cooling down to 1 °C, while NaV1.8-positive neurons are likely responsible for the transduction of prolonged extreme cold temperatures, where tissue damage causes pan-nociceptor activation.

Chemotherapy-induced neuronal dysfunction in the absence of axon degeneration.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15091-e15091
Author(s):  
Stephen Nick Housley ◽  
Ann Marie Flores ◽  
Allison B. Wang ◽  
Eric J. Perreault ◽  
Paul Nardelli ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Neuronal Degeneration ◽  
Transcriptional Profiling ◽  
Immunohistochemical Analysis ◽  
Conclusive Evidence ◽  
Nerve Degeneration ◽  
Axon Degeneration ◽  
Molecular Evidence ◽  
Platinum Based Chemotherapy

e15091 Background: Colorectal cancer is one of the three most prevalent cancers. Mortality rates have largely decreased due, in part, to advanced treatments such as platinum-based chemotherapy (e.g. oxaliplatin – OX). Unfortunately, OX induces severe off-target, neurotoxic side-effects in the sensory nervous system that can limit or end treatment and diminish patient quality of life for years. Patient symptoms are often attributed to dying-back degeneration of primary sensory axons despite the absence of conclusive evidence. We tested the hypothesis that proprioceptive disorders persisting after chemotherapy result solely from axon degeneration of muscle proprioceptors. Methods: We used a rat model to test our hypothesis. In a rodent model of OX clinical cancer treatment, one that exhibits sensorimotor deficits in a test of proprioceptive behavior, we performed single-neuron in vivo electrophysiological and immunohistological experiments. We then profiled transcriptomes of sensory neurons to gain unbiased insight into molecular evidence of degeneration. We compared the OX group of rats (n = 18) to healthy, control rats (n = 6) using hierarchical Bayesian analysis. Results: We found no evidence for sensory axon degeneration in electrophysiologic measures of axon conduction or in immunohistochemical analysis of the axon terminals of sensory neurons, OX and control rats were indistinguishable by these measures. Unbiased transcriptional profiling gave little evidence of neuronal degeneration, although genes related to axon transport showed signs of dysregulation. Structural degeneration was also ruled out by finding that all sensory neurons fired in response to stretch. Nonetheless, anomalous firing patterns were observed, e.g. decreased spike activity in response to mechanosensory stimulation, consistent with changes in ion channel physiology. Conclusions: Our findings reject the hypothesis that nerve degeneration is required to explain OX-related sensorimotor disorders. Our research suggests biological mechanisms that are alternative to axon degeneration in explaining sensorimotor changes due to OX.

Role of calcitonin gene-related peptide in capsaicin-induced gastric submucosal arteriolar dilation

1992 ◽  
Vol 262 (5) ◽  
pp. H1350-H1355 ◽  
Author(s):  
R. Y. Chen ◽  
D. S. Li ◽  
P. H. Guth
Keyword(s):  
Sensory Neurons ◽  
Calcitonin Gene Related Peptide ◽  
Maximal Response ◽  
Related Peptide ◽  
Resistance Vessels ◽  
Basal Tone ◽  
Calcitonin Gene ◽  
Topical Capsaicin ◽  
Dose Dependent

The response of gastric submucosal arterioles to topical (submucosal) application of calcitonin-gene-related peptide (CGRP) or capsaicin with and without the human CGRP antagonist, hCGRP-(8-37), was studied using in vivo microscopy. CGRP (10(-11) to 10(-8) M) induced dose-dependent dilation. Topical treatment with hCGRP(8-37) (10(-6) M, for 10 min) caused a significant decrease in basal arteriolar diameter from 33 +/- 2 to 27 +/- 2 microns. hCGRP(8-37) did not alter acetylcholine- or adenosine-induced vasodilation but did significantly reduce CGRP 10(-8) M vasodilation from 97.3 +/- 10.1 to 15.9 +/- 4.4% of the maximal response. Topical capsaicin (10(-9) M to 5 x 10(-7) M) induced dose-dependent arteriolar dilation. This vasodilation was markedly attenuated by hCGRP(8-37). Selective ablation of capsaicin-sensitive sensory neurons nearly completely inhibited capsaicin-induced vasodilation, suggesting that this vasodilation is primarily neurogenic in origin. We conclude that 1) topical application of capsaicin stimulates capsaicin-sensitive sensory neurons and induces dose-dependent arteriolar dilation; 2) this vasodilation is mediated in part by CGRP; and 3) CGRP may be involved in modulating the basal tone of gastric resistance vessels.

scholarly journals Effect of extreme cold temperatures on quasi-static indentation and impact behavior of woven carbon fiber epoxy composite sandwich panels with nomex honeycomb core

2021 ◽  
pp. 109963622199387
Author(s):  
Mathilde Jean-St-Laurent ◽  
Marie-Laure Dano ◽  
Marie-Josée Potvin
Keyword(s):  
Epoxy Composite ◽  
Impact Behavior ◽  
Effect Of Temperature ◽  
Cold Temperatures ◽  
Composite Sandwich Panels ◽  
Composite Sandwich ◽  
Static Indentation ◽  
Nomex Honeycomb ◽  
Extreme Cold ◽  
The Impact

The effect of extreme cold temperatures on the quasi-static indentation and the low velocity impact behavior of woven carbon/epoxy composite sandwich panels with Nomex honeycomb core was investigated. Impact tests were performed at room temperature, –70°C, and –150°C. Two sizes of hemispherical impactor were used combined to three different impactor masses. All the impact tests were performed at the same initial impact velocity. The effect of temperature on the impact behavior is investigated by studying the load history, load-displacement curves and transmitted energy as a function of time curves. Impact damage induced at various temperatures was studied using different non-destructive and destructive techniques. Globally, more damages are induced with impact temperature decreasing. The results also show that the effect of temperature on the impact behavior is function of the impactor size.

scholarly journals Transcriptional Profiling of Porcine Blastocysts Produced In Vitro in a Chemically Defined Culture Medium

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1414
Author(s):  
Josep M. Cambra ◽  
Emilio A. Martinez ◽  
Heriberto Rodriguez-Martinez ◽  
Maria A. Gil ◽  
Cristina Cuello
Keyword(s):  
Culture Medium ◽  
Embryo Quality ◽  
Transcriptional Profiling ◽  
Defined Medium ◽  
Platelet Factor ◽  
Defined Media ◽  
Defined Culture ◽  
The Impact

The development of chemically defined media is a growing trend in in vitro embryo production (IVP). Recently, traditional undefined culture medium with bovine serum albumin (BSA) has been successfully replaced by a chemically defined medium using substances with embryotrophic properties such as platelet factor 4 (PF4). Although the use of this medium sustains IVP, the impact of defined media on the embryonic transcriptome has not been fully elucidated. This study analyzed the transcriptome of porcine IVP blastocysts, cultured in defined (PF4 group) and undefined media (BSA group) by microarrays. In vivo-derived blastocysts (IVV group) were used as a standard of maximum embryo quality. The results showed no differentially expressed genes (DEG) between the PF4 and BSA groups. However, a total of 2780 and 2577 DEGs were detected when comparing the PF4 or the BSA group with the IVV group, respectively. Most of these genes were common in both in vitro groups (2132) and present in some enriched pathways, such as cell cycle, lysosome and/or metabolic pathways. These results show that IVP conditions strongly affect embryo transcriptome and that the defined culture medium with PF4 is a guaranteed replacement for traditional culture with BSA.

scholarly journals The Trithorax group protein ASH1 requires a combination of BAH domain and AT hooks, but not the SET domain, for mitotic chromatin binding and survival

Chromosoma ◽  
2021 ◽  
Author(s):  
Philipp A. Steffen ◽  
Christina Altmutter ◽  
Eva Dworschak ◽  
Sini Junttila ◽  
Attila Gyenesei ◽  
...  
Keyword(s):  
Transcriptional Profiling ◽  
Histone H3 ◽  
Chromatin Binding ◽  
Set Domain ◽  
Trithorax Group ◽  
Trxg Protein ◽  
Group Protein ◽  
Bah Domain ◽  
Mitotic Chromatin

AbstractThe Drosophila Trithorax group (TrxG) protein ASH1 remains associated with mitotic chromatin through mechanisms that are poorly understood. ASH1 dimethylates histone H3 at lysine 36 via its SET domain. Here, we identify domains of the TrxG protein ASH1 that are required for mitotic chromatin attachment in living Drosophila. Quantitative live imaging demonstrates that ASH1 requires AT hooks and the BAH domain but not the SET domain for full chromatin binding in metaphase, and that none of these domains are essential for interphase binding. Genetic experiments show that disruptions of the AT hooks and the BAH domain together, but not deletion of the SET domain alone, are lethal. Transcriptional profiling demonstrates that intact ASH1 AT hooks and the BAH domain are required to maintain expression levels of a specific set of genes, including several involved in cell identity and survival. This study identifies in vivo roles for specific ASH1 domains in mitotic binding, gene regulation, and survival that are distinct from its functions as a histone methyltransferase.

scholarly journals Functional regeneration and repair of tendons using biomimetic scaffolds loaded with recombinant periostin

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu Wang ◽  
Shanshan Jin ◽  
Dan Luo ◽  
Danqing He ◽  
Chunyan Shi ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Transcriptional Profiling ◽  
Collagen Scaffold ◽  
Defect Model ◽  
Tendon Regeneration ◽  
Biomimetic Scaffolds ◽  
Functional Regeneration

AbstractTendon injuries disrupt the balance between stability and mobility, causing compromised functions and disabilities. The regeneration of mature, functional tendons remains a clinical challenge. Here, we perform transcriptional profiling of tendon developmental processes to show that the extracellular matrix-associated protein periostin (Postn) contributes to the maintenance of tendon stem/progenitor cell (TSPC) functions and promotes tendon regeneration. We show that recombinant periostin (rPOSTN) promotes the proliferation and stemness of TSPCs, and maintains the tenogenic potentials of TSPCs in vitro. We also find that rPOSTN protects TSPCs against functional impairment during long-term passage in vitro. For in vivo tendon formation, we construct a biomimetic parallel-aligned collagen scaffold to facilitate TSPC tenogenesis. Using a rat full-cut Achilles tendon defect model, we demonstrate that scaffolds loaded with rPOSTN promote endogenous TSPC recruitment, tendon regeneration and repair with native-like hierarchically organized collagen fibers. Moreover, newly regenerated tendons show recovery of mechanical properties and locomotion functions.

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