The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However, extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of α9 integrin and its activator kindlin-1 (α9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of adult male rat DRG sensory neurons transduced with α9k1, and controls, with and without axotomy of the central branch. Expression of α9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling α9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration. In addition to the program upregulated by α9k1 expression, regeneration in the spinal cord led to expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum (ER), trafficking, and signaling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPSC-derived sensory neurons, validating their causal contributions to sensory regeneration. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, and Yy1. Signaling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with an additional distinctive program that differs from that involved in PNS regeneration.SIGNIFICANCE STATEMENT Restoration of neurologic function after spinal cord injury has yet to be achieved in human patients. To accomplish this, severed nerve fibers must be made to regenerate. Reconstruction of nerve pathways has not been possible, but recently, a method for stimulating long-distance axon regeneration of sensory fibers in rodents has been developed. This research uses profiling of messenger RNAs in the regenerating sensory neurons to discover which mechanisms are activated. This study shows that the regenerating neurons initiate a novel CNS regeneration program which includes molecular transport, autophagy, ubiquitination, and modulation of the endoplasmic reticulum (ER). The study identifies mechanisms that neurons need to activate to regenerate their nerve fibers.
- MeSH
- axony * fyziologie MeSH
- integriny metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mícha metabolismus MeSH
- nervové receptory fyziologie MeSH
- poranění míchy * terapie metabolismus MeSH
- potkani Sprague-Dawley MeSH
- regenerace nervu fyziologie MeSH
- spinální ganglia metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing.Upper airway cough syndrome (UACS) - previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.
- MeSH
- chronická nemoc MeSH
- kapsaicin škodlivé účinky MeSH
- kašel chemicky indukované patofyziologie MeSH
- kationtové kanály TRPV agonisté fyziologie MeSH
- kationtový kanál TRPA1 agonisté fyziologie MeSH
- lidé MeSH
- nervové receptory účinky léků fyziologie MeSH
- nervus vagus účinky léků patofyziologie MeSH
- nosní sliznice účinky léků patofyziologie MeSH
- syndrom MeSH
- trachea účinky léků patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subservepruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Adelta nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.
- MeSH
- agonisté histaminu škodlivé účinky MeSH
- histamin škodlivé účinky MeSH
- kapsaicin škodlivé účinky MeSH
- kašel chemicky indukované patofyziologie MeSH
- látky ovlivňující senzorický systém škodlivé účinky MeSH
- lidé MeSH
- nervová vlákna myelinizovaná účinky léků fyziologie MeSH
- nervová vlákna nemyelinizovaná účinky léků fyziologie MeSH
- nervové receptory účinky léků fyziologie MeSH
- neurony aferentní účinky léků fyziologie MeSH
- periferní nervy účinky léků patofyziologie MeSH
- pruritus chemicky indukované patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Controlling pain in burn-injured patients poses a major clinical challenge. Recent findings suggest that reducing the activity of the voltage-gated sodium channel Nav1.7 in primary sensory neurons could provide improved pain control in burn-injured patients. Here, we report that partial thickness scalding-type burn injury on the rat paw upregulates Nav1.7 expression in primary sensory neurons 3 h following injury. The injury also induces upregulation in phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), a marker for nociceptive activation in primary sensory neurons. The upregulation in p-CREB occurs mainly in Nav1.7-immunopositive neurons and exhibits a peak at 5 min and, following a decline at 30 min, a gradual increase from 1 h post-injury. The Nav1.7 blocker protoxin II (ProTxII) or morphine injected intraperitoneally 15 min before or after the injury significantly reduces burn injury-induced spinal upregulation in phosphorylated serine 10 in histone H3 and phosphorylated extracellular signal-regulated kinase 1/2, which are both markers for spinal nociceptive processing. Further, ProTxII significantly reduces the frequency of spontaneous excitatory post-synaptic currents in spinal dorsal horn neurons following burn injury. Together, these findings indicate that using Nav1.7 blockers should be considered to control pain in burn injury. KEY MESSAGES: • Burn injury upregulates Nav1.7 expression in primary sensory neurons. • Burn injury results in increased activity of Nav1.7-expressing primary sensory neurons. • Inhibiting Nav1.7 by protoxin II reduces spinal nociceptive processing. • Nav1.7 represents a potential target to reduce pain in burn injury.
- MeSH
- analgetika terapeutické užití MeSH
- blokátory sodíkových kanálů řízených napětím terapeutické užití MeSH
- bolest farmakoterapie MeSH
- mícha cytologie fyziologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- napěťově řízený sodíkový kanál, typ 9 fyziologie MeSH
- nervové receptory fyziologie MeSH
- pavoučí jedy terapeutické užití MeSH
- peptidy terapeutické užití MeSH
- popálení farmakoterapie MeSH
- potkani Sprague-Dawley MeSH
- potkani Wistar MeSH
- protein vázající element responzivní pro cyklický AMP metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Peripheral nerve injury results in profound alterations of the affected neurons resulting from the interplay between intrinsic and extrinsic molecular events. Restarting the neuronal regenerative program is an important prerequisite for functional recovery of the injured peripheral nerve. The primary sensory neurons with their cell bodies in the dorsal root ganglia provide a useful in vivo and in vitro model for studying the mechanisms that regulate intrinsic neuronal regeneration capacity following axotomy. These studies frequently need to indicate the regenerative status of the corresponding neurons. We summarize the critical issues regarding immunohistochemical detection of several regeneration-associated proteins as markers for the initiation of the regeneration program in rat primary sensory neurons and indicators of axon regeneration in the peripheral nerves. This overview also includes our own results of GAP43 and SCG10 expression in different DRG neurons following double immunostaining with molecular markers of neuronal subpopulations (NF200, CGRP, and IB4) as well as transcription factors (ATF3 and activated STAT3) following unilateral sciatic nerve injury. Anat Rec, 301:1618-1627, 2018. © 2018 Wiley Periodicals, Inc.
- MeSH
- axony metabolismus MeSH
- biologické markery metabolismus MeSH
- fyziologický stres MeSH
- korneocytární obal - proteiny bohaté na prolin metabolismus MeSH
- membránové proteiny metabolismus MeSH
- mikrotubulární proteiny MeSH
- nervové receptory klasifikace fyziologie MeSH
- protein GAP-43 metabolismus MeSH
- regenerace nervu * MeSH
- spinální ganglia cytologie metabolismus MeSH
- transportní proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Localization of sound source azimuth within horizontal plane uses interaural time differences (ITDs) between sounds arriving through the left and right ear. In mammals, ITDs are processed primarily in the medial superior olive (MSO) neurons. These are the first binaural neurons in the auditory pathway. The MSO neurons are notable because they possess high time precision in the range of tens of microseconds. Several theories and experimental studies explain how neurons are able to achieve such precision. In most theories, neuronal coincidence detection processes the ITDs and encodes azimuth in ascending neurons of the auditory pathway using modalities that are more tractable than the ITD. These modalities have been described as firing rate codes, place codes (labeled line codes) and similarly. In this theoretical model it is described how the ITD is processed by coincidence detection and converted into spikes by summing the postsynaptic potentials. Particular postsynaptic conductance functions are used in order to obtain an analytical solution in a closed form. Specifically, postsynaptic response functions are derived from the exponential decay of postsynaptic conductances and the MSO neuron is modeled as a simplified version of the Spike Response Model (SRM0) which uses linear summations of the membrane responses to synaptic inputs. For plausible ratios of time constants, an analytical solution used to describe properties of coincidence detection window is obtained. The parameter space is then explored in the vicinity of the analytical solution. The variation of parameters does not change the solution qualitatively.
- MeSH
- akční potenciály fyziologie MeSH
- lidé MeSH
- lokalizace zvuku fyziologie MeSH
- modely neurologické * MeSH
- nervová síť fyziologie MeSH
- nervové receptory fyziologie MeSH
- nervový přenos fyziologie MeSH
- počítačová simulace MeSH
- sluchová dráha fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by small-diameter afferents (A-delta fibers) and large-diameter efferents (alpha motoneurons). The effect of limb temperature on CSPs has so far not been assessed. METHODS: In 27 healthy volunteers (11 males; age 22-58 years) we recorded median nerve motor and sensory action potentials, median nerve F-wave and CSPs induced by noxious digit II stimulation in thenar muscles in a baseline condition at room temperature, and after randomly submersing the forearm in 42 °C warm or 15 °C cold water for 20 min each. RESULTS: In cold limbs, distal and proximal motor and sensory latencies as well as F-wave latencies were prolonged. Motor and sensory nerve conduction velocities were reduced. Compound motor and sensory nerve action potential amplitudes did not differ significantly from baseline. CSP onset and end latencies were more delayed than distal and proximal median nerve motor and sensory latencies, whereas CSP duration was not affected. In warm limbs, opposite but smaller changes were seen in nerve conduction studies and CSPs. CONCLUSION: The observed CSP shift "en bloc" towards longer latencies without affecting CSP duration during limb cooling concurs with slower conduction velocity in both afferent and efferent fibers. Disparate conduction slowing in afferents and efferents, however, suggests that nociceptive EMG suppression is mediated by fibers of different size in the afferent than in the efferent arm, indirectly supporting the contribution of A-delta fibers as the main afferent input. SIGNIFICANCE: Limb temperature should be taken into account when testing CSPs in the clinical setting, as different limb temperatures affect CSP latencies more than large-diameter fiber conduction function.
- MeSH
- akční potenciály fyziologie MeSH
- dospělí MeSH
- končetiny fyziologie MeSH
- kůže inervace MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- motorické neurony fyziologie MeSH
- nervová vlákna myelinizovaná fyziologie MeSH
- nervové receptory fyziologie MeSH
- nervové vedení fyziologie MeSH
- nervus medianus fyziologie MeSH
- reflex fyziologie MeSH
- senzorické prahy fyziologie MeSH
- tělesná teplota fyziologie MeSH
- teplota MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- bolest etiologie farmakoterapie klasifikace komplikace MeSH
- chronická nemoc farmakoterapie terapie MeSH
- diabetické neuropatie farmakoterapie komplikace MeSH
- kapsaicin farmakokinetika farmakologie terapeutické užití MeSH
- kationtové kanály TRPV účinky léků MeSH
- lidé MeSH
- mechanoreceptory * fyziologie účinky léků MeSH
- mononeuropatie farmakoterapie komplikace MeSH
- nádory komplikace MeSH
- nedostatek vitaminu D komplikace metabolismus MeSH
- nervové receptory fyziologie účinky léků MeSH
- patologie metody trendy MeSH
- práh bolesti fyziologie účinky léků MeSH
- vrozené, dědičné a novorozenecké nemoci a abnormality farmakoterapie komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Despite complex facial anatomy, transplantation of soft tissues of the entire face, including the maxilla and mandibular segment anterior to the masseter muscle insertion, can be safely performed based on facial vessels alone. Inclusion of hair-bearing scalp requires dissection of the superficial temporal vessels. Unlike other groups, we advocate for supercharging dissected superficial temporal vessels in the preauricular area avoiding difficult dissections in the depth of external auditory canal that presents significant challenges associated with lengthy dissection and bleeding. Neurorrhaphy at the trunk of the facial nerve leads to less targeted postoperative reinnervation, with potential for synkinesis, and whenever possible, individual peripheral facial nerve branches should be reconnected. Adequate planning for integration of the facial allograft requires both complete sensory and motor nerve connection and should be part of each operation. Bilateral external carotid anastomosis may cause a variety of functional problems including oropharyngeal dysfunction and ocular ischemia and hence is not recommended.
- MeSH
- anastomóza chirurgická kontraindikace MeSH
- arteria carotis externa chirurgie MeSH
- arteriae temporales chirurgie MeSH
- čití, cítění fyziologie MeSH
- disekce metody MeSH
- krvácení při operaci prevence a kontrola MeSH
- lidé MeSH
- motorické neurony fyziologie MeSH
- nervové receptory fyziologie MeSH
- nervus facialis fyziologie chirurgie MeSH
- obličej krevní zásobení inervace MeSH
- obličejové svaly krevní zásobení inervace MeSH
- regenerace nervu fyziologie MeSH
- skalp transplantace MeSH
- synkineze prevence a kontrola MeSH
- transplantace obličeje metody MeSH
- zákroky plastické chirurgie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
While seeking food sources and routes back to their hive, bees make use of their advanced nervous and sensory capacities, which underlie a diverse behavioral repertoire. One of several honeybee senses that is both exceptional and intriguing is magnetoreception - the ability to perceive the omnipresent magnetic field (MF) of the Earth. The mechanism by which animals sense MFs has remained fascinating as well as elusive because of the intricacies involved, which makes it one of the grand challenges for neural and sensory biology. However, investigations in recent years have brought substantial progress to our understanding of how such magneto-receptor(s) may work. Some terrestrial animals (birds) are reported to be equipped even with a dual perception system: one based on diminutive magnetic particles - in line with the original model which has also always been hypothesized for bees - and the other one, as the more recent model describes, based on a sensitivity of some photochemical reactions to MF (radical-pair or chemical mechanism). The latter model postulates a close link to vision and supposes that the animals can see the position of the geomagnetic North as a visible pattern superimposed on the picture of the environment. In recent years, a growing body of evidence has shown that radical-pair magnetoreception might also be used by insects. It is realistic to expect that such evidence will inspire a re-examination and extension or confirmation of established views on the honeybee magnetic-compass mechanism. However, the problem of bee magnetoreception will not be solved at the moment that a receptor is discovered. On the contrary, the meaning of magnetoreception in insect life and its involvement in the orchestration of other senses is yet to be fully understood. The crucial question to be addressed in the near future is whether the compass abilities of the honeybee could suffer from radio frequency (RF) smog accompanying modern civilization and whether the fitness of this dominant pollinator might be affected by RF fields. The goal of this review is to provide an overview of the path that the behavioral research on honeybee magnetoreception has taken and to discuss it in the context of contemporary data obtained on other insects.
- MeSH
- chování zvířat fyziologie MeSH
- čití, cítění MeSH
- elektromagnetické záření MeSH
- hmyz fyziologie MeSH
- magnetické jevy MeSH
- magnetické pole MeSH
- nervové receptory fyziologie MeSH
- ptáci fyziologie MeSH
- rádiové vlny škodlivé účinky MeSH
- teritoriální chování fyziologie MeSH
- včely fyziologie MeSH
- železo fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH