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1.
Biol Pharm Bull ; 42(10): 1741-1745, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582662

RESUMO

Our previous studies have shown that phenylephrine-induced contraction of cutaneous arteries is primarily mediated via α1A-adrenoceptors, but not α1D-adrenoceptors that generally mediate vascular contraction, and that the larger part of the contraction is induced in a voltage-dependent Ca2+ channel (VDCC)-independent manner. Here, we investigated the mechanism underlying the smaller part of the α1A-adrenoceptor-mediated contraction, i.e., VDCC-dependent one, in cutaneous arteries. Isometric contraction was measured with wire myograph in endothelium-denuded tail and iliac arterial rings isolated from male Wistar rats. LOE908 (10 µM), a cation channel blocker, partially inhibited the contraction induced by phenylephrine in tail and iliac arteries. Nifedipine (10 µM) further suppressed the phenylephrine-induced contraction that remained in the presence of LOE908 (10 µM) in iliac arteries but barely in tail arteries, suggesting that phenylephrine-induced depolarization in tail arteries is due to the activation of LOE908-sensitive cation channels. In iliac arteries, the contraction induced by A-61603, a specific α1A-adrenoceptor agonist, was also partially inhibited by LOE908 (10 µM); however, nifedipine had little effect on the A-61603-induced contraction that remained in the presence of LOE908 (10 µM), suggesting that depolarization mediated via α1A-adrenoceptors is due to the activation of LOE908-sensitive cation channels even in iliac arteries. These results suggest that membrane depolarization mediated via α1Α-adrenoceptors is caused by cation influx through LOE908-sensitive cation channels. Less contribution of VDCC to phenylephrine-induced contraction in tail arteries compared to in iliac arteries is likely due to that α1Α-adrenoceptor-mediated activation of VDCC is caused only by depolarization via cation influx through LOE908-sensitive cation channels.


Assuntos
Canais de Cálcio/fisiologia , Artéria Ilíaca/fisiologia , Receptores Adrenérgicos alfa 1/fisiologia , Cauda/irrigação sanguínea , Acetamidas/farmacologia , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Imidazóis/farmacologia , Isoquinolinas/farmacologia , Masculino , Nifedipino/farmacologia , Fenilefrina/farmacologia , Ratos Wistar , Cauda/fisiologia , Tetra-Hidronaftalenos/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
2.
Sensors (Basel) ; 19(15)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31357572

RESUMO

This study aims to characterize traumatic spinal cord injury (TSCI) neurophysiologically using an intramuscular fine-wire electromyography (EMG) electrode pair. EMG data were collected from an agonist-antagonist pair of tail muscles of Macaca fasicularis, pre- and post-lesion, and for a treatment and control group. The EMG signals were decomposed into multi-resolution subsets using wavelet transforms (WT), then the relative power (RP) was calculated for each individual reconstructed EMG sub-band. Linear mixed models were developed to test three hypotheses: (i) asymmetrical volitional activity of left and right side tail muscles (ii) the effect of the experimental TSCI on the frequency content of the EMG signal, (iii) and the effect of an experimental treatment. The results from the electrode pair data suggested that there is asymmetry in the EMG response of the left and right side muscles (p-value < 0.001). This is consistent with the construct of limb dominance. The results also suggest that the lesion resulted in clear changes in the EMG frequency distribution in the post-lesion period with a significant increment in the low-frequency sub-bands (D4, D6, and A6) of the left and right side, also a significant reduction in the high-frequency sub-bands (D1 and D2) of the right side (p-value < 0.001). The preliminary results suggest that using the RP of the EMG data, the fine-wire intramuscular EMG electrode pair are a suitable method of monitoring and measuring treatment effects of experimental treatments for spinal cord injury (SCI).


Assuntos
Músculo Esquelético/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico por imagem , Ferimentos e Lesões/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Eletrodos Implantados , Eletromiografia , Humanos , Macaca fascicularis , Músculo Esquelético/fisiologia , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Cauda/fisiologia , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/fisiopatologia
3.
J Therm Biol ; 83: 54-59, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331525

RESUMO

The aim of this study was to examine the effect of estradiol (E2) on the thermoregulatory responses induced by cinnamaldehyde, a component extracted from cinnamon at 16 °C or 27 °C. The thermoneutral and subneutral experiments were performed to evaluate the augmented effect of cinnamaldehyde by cold exposure and the effect of cinnamaldehyde itself. Ovariectomized rats were implanted with a silastic tube with or without E2 (E2(+) and E2(-) groups), and data loggers into the peritoneal cavity. After the application of 30% cinnamaldehyde or vehicle into the skin of the whole trunk of rats, the rats were exposed to 16 °C or 27 °C for 2 h. Body temperature (Tb) and tail temperature (Ttail) were measured using a data logger and thermography. After exposure, blood samples were obtained, and plasma catecholamine concentration were measured by high-performance liquid chromatography. In the E2(-) group exposed to 27 °C, the change in Tb in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle. The change in Ttail in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle in both E2(-) and E2(+) groups at 27 °C and 16 °C. Plasma catecholamine concentration at 27 °C was not different among the groups. E2 might not affect thermoregulatory responses induced by cinnamaldehyde application; however, it decreased Ttail in female rats.


Assuntos
Acroleína/análogos & derivados , Temperatura Corporal/efeitos dos fármacos , Estradiol/farmacologia , Acroleína/farmacologia , Animais , Regulação da Temperatura Corporal , Feminino , Ratos , Ratos Wistar , Cauda/fisiologia
4.
Zool Res ; 40(5): 416-426, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31111695

RESUMO

Ephrin receptors are the most common tyrosine kinase effectors operating during development. Ephrin receptor genes are reported to be up-regulated in the regenerating tail of the Podarcis muralis lizard. Thus, in the current study, we investigated immunolocalization of ephrin receptors in the Podarcis muralis tail during regeneration. Weak immunolabelled bands for ephrin receptors were detected at 15-17 kDa, with a stronger band also detected at 60-65 kDa. Labelled cells and nuclei were seen in the basal layer of the apical wound epidermis and ependyma, two key tissues stimulating tail regeneration. Strong nuclear and cytoplasmic labelling were present in the segmental muscles of the regenerating tail, sparse blood vessels, and perichondrium of regenerating cartilage. The immunolocalization of ephrin receptors in muscle that gives rise to large portions of new tail tissue was correlated with their segmentation. This study suggests that the high localization of ephrin receptors in differentiating epidermis, ependyma, muscle, and cartilaginous cells is connected to the regulation of cell proliferation through the activation of programs for cell differentiation in the proximal regions of the regenerating tail. The lower immunolabelling of ephrin receptors in the apical blastema, where signaling proteins stimulating cell proliferation are instead present, helps maintain the continuous growth of this region.


Assuntos
Imuno-Histoquímica , Lagartos/fisiologia , Receptores da Família Eph/metabolismo , Regeneração/fisiologia , Cauda/fisiologia , Animais , Receptores da Família Eph/genética
5.
Science ; 364(6441): 653-658, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31097661

RESUMO

Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing after tail amputation. By comparing naturally occurring regeneration-competent and -incompetent tadpoles, we identified a previously unrecognized cell type, which we term the regeneration-organizing cell (ROC). ROCs are present in the epidermis during normal tail development and specifically relocalize to the amputation plane of regeneration-competent tadpoles, forming the wound epidermis. Genetic ablation or manual removal of ROCs blocks regeneration, whereas transplantation of ROC-containing grafts induces ectopic outgrowths in early embryos. Transcriptional profiling revealed that ROCs secrete ligands associated with key regenerative pathways, signaling to progenitors to reconstitute lost tissue. These findings reveal the cellular mechanism through which ROCs form the wound epidermis and ensure successful regeneration.


Assuntos
Epiderme/fisiologia , Reepitelização/fisiologia , Cauda/fisiologia , Xenopus laevis/fisiologia , Animais , Células Epidérmicas/fisiologia , Reepitelização/genética , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Transcriptoma , Proteínas de Xenopus/genética , Xenopus laevis/genética
6.
J Ethnopharmacol ; 237: 64-73, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30902745

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Disposed earthworm has been used to treat various common ailments including burns, arthritis, itching, and inflammation for thousands of years in China. As their remarkable ability to fully regenerate in a scar-free manner, regenerated tissue homogenate of amputated Eisenia fetida (E. fetida) have been considered as an excellent wound repair therapy in our previous study. We have demonstrated that regenerated earthworm (G-90') can perform higher wound repair ability to non-regeneration tissue (G-90) through significant promotion of cutaneous wound repair in mice after their administration into wound beds. OBJECTIVE: In the present study, we aimed to reveal the mechanism of G-90' and to explore a potential wound healing accelerated strategy. METHODS AND RESULTS: Two functional proteins- HSP70 and lysozyme in G-90' were confirmed by cross-identification of LC-MS/MS and transcriptome analyses. Followed with semi-quantitative PCR and western blot, their expression were validated to up-regulate in 3-day regenerated tissues (G-90'). CONCLUSION: This study implies the therapeutic potency of G-90' for wound recovery and provides a new strategy to assess other natural materials targeting wound healing with the tail-amputated E .fetida as a model organism.


Assuntos
Proteínas de Choque Térmico HSP70/fisiologia , Muramidase/fisiologia , Oligoquetos/fisiologia , Cicatrização/fisiologia , Animais , Proliferação de Células , Perfilação da Expressão Gênica , Camundongos , Células NIH 3T3 , Regeneração , Cauda/fisiologia , Regulação para Cima
7.
Exp Brain Res ; 237(6): 1551-1561, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30927042

RESUMO

Complexity in movement planning, arising from diverse temporal and spatial sources, places a computational burden on the central nervous system. However, the efficacy with which humans can perform natural, highly trained movements suggests that they have evolved effective behavioral strategies that simplify the computational burden. The specific aim of our research was to use three-dimensional high-speed video to determine whether the tail nociceptive withdrawal response (NWR) to noxious heat stimuli delivered at locations that varied both circumferentially and rostral-caudally on the tail depended on the location of the stimulus in spinalized rats. In particular, we sought to determine whether the movement strategy was categorical (limited number of directions) or continuous (any variation in stimulus location results in a variation in response direction). In spinalized rats, localized, noxious heat stimuli were delivered at eight locations circumferentially around the tail and at five rostral-caudal levels. Our results demonstrate that at all rostral-caudal levels, response movement direction was bimodal regardless of circumferential stimulus location-either ~ 64° left or right of ventral. However, in spite of tight clustering, movement direction varied significantly but weakly according to circumferential location, in that responses to stimuli were more lateral for lateral stimulus locations. In contrast, changes in stimulus level strongly affected movement direction, in that a localized bend response closely matched the level of the stimulus. Together, our results demonstrate, based on movement analysis in spinalized rats, that the NWR employs a hybrid categorical-continuous strategy that may minimize the harmful consequences of noxious stimuli.


Assuntos
Comportamento Animal/fisiologia , Movimento/fisiologia , Nociceptividade/fisiologia , Cauda/fisiologia , Animais , Masculino , Estimulação Física , Ratos , Ratos Sprague-Dawley , Medula Espinal/cirurgia , Temperatura
8.
Development ; 146(4)2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30696711

RESUMO

Amphioxus, a cephalochordate, is an ideal animal in which to address questions about the evolution of regenerative ability and the mechanisms behind the invertebrate to vertebrate transition in chordates. However, the cellular and molecular basis of tail regeneration in amphioxus remains largely ill-defined. We confirmed that the tail regeneration of amphioxus Branchiostoma japonicum is a vertebrate-like epimorphosis process. We performed transcriptome analysis of tail regenerates, which provided many clues for exploring the mechanism of tail regeneration. Importantly, we showed that BMP2/4 and its related signaling pathway components are essential for the process of tail regeneration, revealing an evolutionarily conserved genetic regulatory system involved in regeneration in many metazoans. We serendipitously discovered that bmp2/4 expression is immediately inducible by general wounds and that expression of bmp2/4 can be regarded as a biomarker of wounds in amphioxus. Collectively, our results provide a framework for understanding the evolution and diversity of cellular and molecular events of tail regeneration in vertebrates.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/metabolismo , Anfioxos/fisiologia , Regeneração , Transdução de Sinais , Cauda/fisiologia , Animais , Apoptose , Evolução Biológica , Biomarcadores/metabolismo , Proliferação de Células , Evolução Molecular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Filogenia , Análise de Sequência de RNA , Cicatrização
9.
Zebrafish ; 16(2): 214-216, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30615594

RESUMO

Recently, the evaluation of spontaneous tail movement (STM) in zebrafish embryos has been proposed as a possible neurotoxicity marker in studies on behavioral changes due to chemical exposure. Currently, automated STM quantification can only be performed using high-cost commercial software. We have developed a simple and reliable MATLAB® script called ZebraSTM that allows the automatic analysis of STM in multiple zebrafish embryos.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Atividade Motora , Cauda/fisiologia , Peixe-Zebra/fisiologia , Animais , Embrião não Mamífero/fisiologia , Processamento de Imagem Assistida por Computador/instrumentação , Ciência dos Animais de Laboratório/métodos , Software , Gravação em Vídeo/instrumentação , Gravação em Vídeo/métodos
10.
Dev Dyn ; 248(2): 189-196, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30569660

RESUMO

BACKGROUND: Among vertebrates, salamanders are unparalleled in their ability to regenerate appendages throughput life. However, little is known about early signals that initiate regeneration in salamanders. RESULTS: Ambystoma mexicanum embryos were administered tail amputations to investigate the timing of reactive oxygen species (ROS) production and the requirement of ROS for regeneration. ROS detected by dihydroethidium increased within minutes of axolotl tail amputation and levels remained high for 24 hr. Pharmacological inhibition of ROS producing enzymes with diphenyleneiodonium chloride (DPI) and VAS2870 reduced ROS levels. Furthermore, DPI treatment reduced cellular proliferation and inhibited tail outgrowth. CONCLUSIONS: The results show that ROS levels increase in response to injury and are required for tail regeneration. These findings suggest that ROS provide instructive, if not initiating cues, for salamander tail regeneration. Developmental Dynamics 248:189-196, 2019. © 2018 Wiley Periodicals, Inc.


Assuntos
Ambystoma mexicanum/fisiologia , Amputação , Espécies Reativas de Oxigênio/metabolismo , Regeneração , Ambystoma mexicanum/embriologia , Animais , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/farmacologia , Regeneração/efeitos dos fármacos , Transdução de Sinais , Cauda/crescimento & desenvolvimento , Cauda/fisiologia , Urodelos
11.
Zoology (Jena) ; 131: 1-9, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30502822

RESUMO

Tail regeneration in lizard is stimulated from the apical epidermis and spinal cord, the principal sources of growth factors and signaling proteins that sustain regeneration. Immunolabeling shows that serpins (serine protease inhibitors), which genes are among those most up-regulated during tail regeneration, are prevalently immunolocalized in the regenerating epidermis and ependyma. Western blot detects main protein bands extracted from regenerating tail at 25-27 and 48-52 kDa. The former band may correspond to p27 serpin, a degraded immunogenic fragment of serpin detected in psoriasis and cancer. This suggests that also in lizard the degradation of these proteins occurs but is uncertain whether it is physiological with some function or the fragments derive from the extractive process. In the regenerating epidermis serpins are mainly accumulated in pre-corneous and corneous layers (alpha-layers), and also in the forming oberhautchen and hard beta-layer. In the tail tip serpin-immunolabeling is mainly seen in the ependymal tube and with lower intensity in blastema (mesenchymal) cells. Aside the control on endogenous proteases for the formation of a protective corneous barrier, serpins may also form a protective anti-microbial barrier for the ependyma. The protection of the epidermis and ependyma allows these tissue to continue the stimulation for tail regeneration.


Assuntos
Células Epidérmicas/metabolismo , Lagartos/fisiologia , Regeneração/fisiologia , Serpinas/metabolismo , Cauda/fisiologia , Animais , Western Blotting , Diferenciação Celular , Epiderme/metabolismo , Transporte Proteico , Medula Espinal
12.
Front Neural Circuits ; 12: 95, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30420798

RESUMO

In larval xenopus, locomotor-induced oculomotor behavior produces gaze-stabilizing eye movements to counteract the disruptive effects of tail undulation during swimming. While neuronal circuitries responsible for feed-forward intrinsic spino-extraocular signaling have recently been described, the resulting oculomotor behavior remains poorly understood. Conveying locomotor CPG efference copy, the spino-extraocular motor command coordinates the multi-segmental rostrocaudal spinal rhythmic activity with the extraocular motor activity. By recording sequences of xenopus tadpole free swimming, we quantified the temporal calibration of conjugate eye movements originating from spino-extraocular motor coupled activity during pre-metamorphic tail-based undulatory swimming. Our results show that eye movements are produced only during robust propulsive forward swimming activity and increase with the amplitude of tail movements. The use of larval isolated in vitro and semi-intact fixed head preparations revealed that spinal locomotor networks driving the rostral portion of the tail set the precise timing of the spino-extraocular motor coupling by adjusting the phase relationship between spinal segment and extraocular rhythmic activity with the swimming frequency. The resulting spinal-evoked oculomotor behavior produced conjugated eye movements that were in phase opposition with the mid-caudal part of the tail. This time adjustment is independent of locomotor activity in the more caudal spinal parts of the tail. Altogether our findings demonstrate that locomotor feed-forward spino-extraocular signaling produce conjugate eye movements that compensate specifically the undulation of the mid-caudal tail during active swimming. Finally, this study constitutes the first extensive behavioral quantification of spino-extraocular motor coupling, which sets the basis for understanding the mechanisms of locomotor-induced oculomotor behavior in larval frog.


Assuntos
Fixação Ocular/fisiologia , Larva/fisiologia , Locomoção/fisiologia , Músculos Oculomotores/fisiologia , Natação/fisiologia , Cauda/fisiologia , Animais , Movimentos Oculares/fisiologia , Fatores de Tempo , Xenopus laevis
13.
Artigo em Inglês | MEDLINE | ID: mdl-30353372

RESUMO

Feeding is important to supply the immediate energy needs of animals and starved animals must expend energy in attempting to acquire foods irrespective of the danger of predation risk. Crayfish escape from attack of predators by tailflipping and in response to rostral stimuli crayfish show backward escape swimming following an initial rapid flexion of the abdomen. Since the tailflip is an energetically costly behaviour, the occurrence of a tailflip diminishes if a stimulus is repeatedly applied through habituation. In this study, we have compared the process of this habituation between fed and starved crayfish. We found that in starved animals habituation was enhanced compared to fed animals. The presence of food in the experimental tanks further enhanced habituation of starved animals. Starved crayfish thus showed trade-offs between energy saving and predation risk.


Assuntos
Astacoidea , Reação de Fuga , Habituação Psicofisiológica , Natação , Animais , Astacoidea/fisiologia , Ingestão de Alimentos , Reação de Fuga/fisiologia , Feminino , Alimentos , Habituação Psicofisiológica/fisiologia , Masculino , Atividade Motora/fisiologia , Inanição/fisiopatologia , Natação/fisiologia , Cauda/fisiologia
14.
J Exp Biol ; 221(Pt 20)2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30323113

RESUMO

The swinging of a mammal's tail has long been thought to deter biting insects, which, in cows, can drain up to 0.3 liters of blood per day. How effective is a mammal's tail at repelling insects? In this combined experimental and theoretical study, we filmed horses, zebras, elephants, giraffes and dogs swinging their tails. The tail swings at triple the frequency of a gravity-driven pendulum, and requires 27 times more power input. Tails can also be used like a whip to directly strike at insects. This whip-like effect requires substantial torques from the base of the tail on the order of 101-102 N m, comparable to the torque of a sedan, but still within the physical limits of the mammal. Based on our findings, we designed and built a mammal tail simulator to simulate the swinging of the tail. The simulator generates mild breezes of 1 m s-1, comparable to a mosquito's flight speed, and sufficient to deter up to 50% of mosquitoes from landing. This study may help us determine new mosquito-repelling strategies that do not depend on chemicals.


Assuntos
Movimentos do Ar , Mamíferos/fisiologia , Movimento , Cauda/fisiologia , Animais , Fenômenos Biomecânicos
15.
Nat Commun ; 9(1): 4296, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30327466

RESUMO

Redox state sustained by reactive oxygen species (ROS) is crucial for regeneration; however, the interplay between oxygen (O2), ROS and hypoxia-inducible factors (HIF) remains elusive. Here we observe, using an optic-based probe (optrode), an elevated and steady O2 influx immediately upon amputation. The spatiotemporal O2 influx profile correlates with the regeneration of Xenopus laevis tadpole tails. Inhibition of ROS production but not ROS scavenging decreases O2 influx. Inhibition of HIF-1α impairs regeneration and stabilization of HIF-1α induces regeneration in the refractory period. In the regeneration bud, hypoxia correlates with O2 influx, ROS production, and HIF-1α stabilization that modulate regeneration. Further analyses reveal that heat shock protein 90 is a putative downstream target of HIF-1α while electric current reversal is a de facto downstream target of HIF-1α. Collectively, the results show a mechanism for regeneration via the orchestration of O2 influx, ROS production, and HIF-1α stabilization.


Assuntos
Oxigênio/metabolismo , Regeneração/fisiologia , Cauda/fisiologia , Xenopus laevis/fisiologia , Animais , Animais Geneticamente Modificados , Benzoquinonas/farmacologia , Hipóxia Celular , Equinomicina/farmacologia , Feminino , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lactamas Macrocíclicas/farmacologia , Larva/metabolismo , Larva/fisiologia , Masculino , Camundongos Mutantes , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Regeneração/efeitos dos fármacos , Pele/lesões , Pele/metabolismo , Cauda/lesões , Proteínas de Xenopus/metabolismo
16.
Nat Commun ; 9(1): 4010, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30275454

RESUMO

Many aquatic vertebrates have a remarkable ability to regenerate limbs and tails after amputation. Previous studies indicate that reactive oxygen species (ROS) signalling initiates regeneration, but the mechanism by which this takes place is poorly understood. Developmental signalling pathways have been shown to have proregenerative roles in many systems. However, whether these are playing roles that are specific to regeneration, or are simply recapitulating their developmental functions is unclear. Here, we analyse zebrafish larval tail regeneration and find evidence that ROS released upon wounding cause repositioning of notochord cells to the damage site. These cells secrete Hedgehog ligands that are required for regeneration. Hedgehog signalling is not required for normal tail development suggesting that it has a regeneration-specific role. Our results provide a model for how ROS initiate tail regeneration, and indicate that developmental signalling pathways can play regenerative functions that are not directly related to their developmental roles.


Assuntos
Proteínas Hedgehog/genética , Notocorda/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regeneração , Cauda/fisiologia , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/fisiologia , Animais , Movimento Celular , Regulação da Expressão Gênica , Proteínas Hedgehog/metabolismo , Modelos Biológicos , Notocorda/citologia , Regeneração/genética , Transdução de Sinais/genética , Cauda/metabolismo , Cicatrização/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Quinases da Família src/antagonistas & inibidores
17.
Zool Res ; 39(6): 413-423, 2018 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-29976844

RESUMO

Lizards are key amniote models for studying organ regeneration. During tail regeneration in lizards, blastemas contain sparse granulocytes, macrophages, and lymphocytes among the prevalent mesenchymal cells. Using transmission electron microscopy to examine scarring blastemas after third and fourth sequential tail amputations, the number of granulocytes, macrophages, and lymphocytes increased at 3-4 weeks in comparison to the first regeneration. An increase in granulocytes and agranulocytes also occurred within a week after blastema cauterization during the process of scarring. Blood at the third and fourth regeneration also showed a significant increase in white blood cells compared with that under normal conditions and at the first regeneration. The extracellular matrix of the scarring blastema, especially after cauterization, was denser than that in the normal blastema and numerous white blood cells and fibroblasts were surrounded by electron-pale, fine fibrinoid material mixed with variable collagen fibrils. In addition to previous studies, the present observations support the hypothesis that an increase in inflammation and immune reactions determine scarring rather than regeneration. These new findings verify that an immune reaction against mesenchymal and epidermal cells of the regenerative blastema is one of the main causes for the failure of organ regeneration in amniotes.


Assuntos
Leucócitos/fisiologia , Lagartos/fisiologia , Regeneração/fisiologia , Cauda/fisiologia , Amputação , Animais , Cauterização , Fibroblastos/fisiologia , Lagartos/lesões , Cauda/lesões
18.
Wound Repair Regen ; 26(5): 366-380, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30054965

RESUMO

Lizards are unique in having both-regeneration competent (tail) as well as non-regenerating appendages (limbs) in adults. They therefore present an appropriate model for comparing processes underlying regenerative repair and nonregenerative healing after amputation. In the current study, we use northern house gecko Hemidactylus flaviviridis to compare major cellular and molecular events following amputation of the limb and of the tail. Although the early response to injury in both cases comprises apoptosis, proliferation, and angiogenesis, the temporal distribution of these processes in each remained obscure. In this regard, observations were made on the anatomy and gene expression levels of key regulators of these processes during the healing phase of the tail and limb separately. It was revealed that cell proliferation markers like fibroblast growth factors were upregulated early in the healing tail, coinciding with the growing epithelium. The amputated limb, in contrast, showed weak expression of proliferation markers, limited only to fibroblasts in the later stage of healing. Additionally, apoptotic activity in the tail was limited to the very early phase of healing, as opposed to that in the limb, wherein high expression of caspase-3 was observed throughout the healing process. Early rise in VEGF-α expression reflected an early onset of angiogenesis in the tail, while it was seen to occur at a later stage in case of the limb. Moreover, the expression pattern of transforming growth factor beta members points toward a pro-fibrotic response being induced very early in the amputated limb. Collectively, these results explain why regenerating appendages are able to heal without scars and if we are to induce scar-free healing in nonregenerating limbs, what interventions can be envisaged. This is crucial to the field of regenerative medicine since it is the initial stages of repair following amputation, which decide whether the appendage will be restored or only covered with a scab.


Assuntos
Amputação , Cicatriz/patologia , Extremidades/fisiopatologia , Lagartos , Regeneração/fisiologia , Cauda/fisiologia , Cicatrização , Animais , Proliferação de Células/fisiologia , Extremidades/irrigação sanguínea , Imunomodulação , Modelos Animais , Neovascularização Fisiológica/fisiologia , Medicina Regenerativa , Proteínas de Répteis/genética , Proteínas de Répteis/metabolismo , Cauda/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
J Exp Biol ; 221(Pt 18)2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30026242

RESUMO

Animal locomotion is driven by underlying axial and appendicular musculature. In order for locomotion to be effective, these muscles must be able to rapidly respond to changes in environmental and physiological demands. Although virtually unstudied, muscles must also respond to morphological changes, such as those that occur with tail autotomy in lizards. Tail autotomy in leopard geckos (Eublepharis macularius) results in a 25% loss of caudal mass and significant kinematic alterations to maintain stability. To elucidate how motor control of the locomotor muscles is modulated with these shifts, we used electromyography (EMG) to quantify patterns of in vivo muscle activity in forelimb and hindlimb muscles before and after autotomy. Forelimb muscles (biceps brachii and triceps brachii) exhibited no changes in motor recruitment, consistent with unaltered kinematics after autotomy. The amplitude of activity of propulsive muscles of the hindlimbs (caudofemoralis and gastrocnemius) was significantly reduced and coincided with decreases in the propulsive phases of femur retraction and ankle extension, respectively. The puboischiotibialis did not exhibit these changes, despite significant reductions in femur depression and knee angle, suggesting that the reduction in mass and vertical ground-reaction force by autotomy allows for the maintenance of a more sprawled and stable posture without increasing motor recruitment of the support muscles. These results highlight the significant neuromuscular shifts that occur to accommodate dramatic changes in body size and mass distribution, and illuminate the utility of tail autotomy as a system for studying the neuromuscular control of locomotion.


Assuntos
Peso Corporal , Lagartos/fisiologia , Locomoção/fisiologia , Músculo Esquelético/fisiologia , Postura/fisiologia , Cauda/fisiologia , Animais , Fenômenos Biomecânicos , Eletromiografia , Membro Anterior/fisiologia , Membro Posterior/fisiologia , Lagartos/cirurgia , Cauda/cirurgia
20.
J Morphol ; 279(8): 1171-1184, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29885003

RESUMO

The formation of the regenerating tail blastema of lizards occurs by the multiplication of stem cells but also some dedifferentiation from adult cells may take place after tail loss by autotomy, as it is suggested in the present study. Using 5BrdU-immunocytochemistry and transmission electron microscopy it is shown that part of the damaged tissues undergo progressive cytological de-differentiation (cell reprogramming). This occurs for muscle, fibrocytes, chondrocytes, adipocytes, and cells derived from the spinal cord during the initial 3-8 days post-autotomy of the tail in the wall lizard Podarcis muralis. Dedifferentiating cells loose most endoplasmic reticulum, sarcomeres in myocells, lipid droplets in adipocytes, extracellular matrix in chondrocytes. Numerous cytoplasmic vesicles are formed, perhaps reflecting an initial sufferance of dedifferentiating cells. These cells are not dying because they incorporate 5BrdU and proliferate. Nuclei of small fibrocytes present in the dermis and inter-muscle connective tissues, initially heterochromatic, become euchromatic and their cytoplasm increases in volume although the endoplasmic reticulum remains limited, as it is typical for mesenchymal cells. The present study, supported by previous transcriptome and 5BrdU-labeling data, and from recent tracing studies, suggests that aside stem cells present in different tissues of the tail, also cell dedifferentiation occurs in the injured tail of lizards. The relative contribution between de-differentiation and stem cells for the formation of the regenerating lizard blastema likely depends from the extension of the trauma.


Assuntos
Diferenciação Celular , Lagartos/fisiologia , Regeneração/fisiologia , Cauda/citologia , Cauda/ultraestrutura , Adipócitos/citologia , Adipócitos/ultraestrutura , Animais , Cartilagem/citologia , Condrócitos , Processamento de Imagem Assistida por Computador , Cauda/fisiologia
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