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1.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206060

RESUMO

Acupuncture modulates the mesolimbic dopamine (DA) system; an area implicated in drug abuse. However, the mechanism by which peripheral sensory afferents, during acupuncture stimulation, modulate this system needs further investigation. The lateral hypothalamus (LH) has been implicated in reward processing and addictive behaviors. To investigate the role of the LH in mediating acupuncture effects, we evaluated the role of LH and spinohypothalamic neurons on cocaine-induced psychomotor activity and NAc DA release. Systemic injection of cocaine increased locomotor activity and 50 kHz ultrasonic vocalizations (USVs), which were attenuated by mechanical stimulation of needles inserted into HT7 but neither ST36 nor LI5. The acupuncture effects were blocked by chemical lesions of the LH or mimicked by activation of LH neurons. Single-unit extracellular recordings showed excitation of LH and spinohypothalamic neurons following acupuncture. Our results suggest that acupuncture recruits the LH to suppress the mesolimbic DA system and psychomotor responses following cocaine injection.


Assuntos
Cocaína/farmacologia , Dopamina/metabolismo , Neurônios Aferentes/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Acupuntura/métodos , Animais , Humanos , Região Hipotalâmica Lateral/efeitos dos fármacos , Região Hipotalâmica Lateral/metabolismo , Locomoção/efeitos dos fármacos , Agulhas , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/patologia , Ratos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/terapia
2.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199392

RESUMO

Coordination of four-limb movements during quadrupedal locomotion is controlled by supraspinal monoaminergic descending pathways, among which serotoninergic ones play a crucial role. Here we investigated the locomotor pattern during recovery from blockade of 5-HT7 or 5-HT2A receptors after intrathecal application of SB269970 or cyproheptadine in adult rats with chronic intrathecal cannula implanted in the lumbar spinal cord. The interlimb coordination was investigated based on electromyographic activity recorded from selected fore- and hindlimb muscles during rat locomotion on a treadmill. In the time of recovery after hindlimb transient paralysis, we noticed a presence of an unusual pattern of quadrupedal locomotion characterized by a doubling of forelimb stepping in relation to unaffected hindlimb stepping (2FL-1HL) after blockade of 5-HT7 receptors but not after blockade of 5-HT2A receptors. The 2FL-1HL pattern, although transient, was observed as a stable form of fore-hindlimb coupling during quadrupedal locomotion. We suggest that modulation of the 5-HT7 receptors on interneurons located in lamina VII with ascending projections to the forelimb spinal network can be responsible for the 2FL-1HL locomotor pattern. In support, our immunohistochemical analysis of the lumbar spinal cord demonstrated the presence of the 5-HT7 immunoreactive cells in the lamina VII, which were rarely 5-HT2A immunoreactive.


Assuntos
Locomoção/genética , Receptor 5-HT2A de Serotonina/genética , Receptores de Serotonina/genética , Traumatismos da Medula Espinal/genética , Animais , Ciproeptadina/farmacologia , Estimulação Elétrica , Eletromiografia , Membro Anterior/efeitos dos fármacos , Membro Anterior/fisiopatologia , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiopatologia , Humanos , Locomoção/efeitos dos fármacos , Região Lombossacral/fisiopatologia , Ratos , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Serotonina/genética , Serotonina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/fisiopatologia
3.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206764

RESUMO

Plant-parasitic nematodes cause severe economic losses annually which has been a persistent problem worldwide. As current nematicides are highly toxic, prone to drug resistance, and have poor stability, there is an urgent need to develop safe, efficient, and green strategies. Natural active polysaccharides such as chitin and chitosan with good biocompatibility and biodegradability and inducing plant disease resistance have attracted much attention, but their application is limited due to their poor solubility. Here, we prepared 6-oxychitin with good water solubility by introducing carboxylic acid groups based on retaining the original skeleton of chitin and evaluated its potential for nematode control. The results showed that 6-oxychitin is a better promoter of the nematicidal potential of Purpureocillium lilacinum than other water-soluble chitin derivatives. After treatment, the movement of J2s and egg hatching were obviously inhibited. Further plant experiments found that it can destroy the accumulation and invasion of nematodes, and has a growth-promoting effect. Therefore, 6-oxychitin has great application potential in the nematode control area.


Assuntos
Antinematódeos/farmacologia , Quitina/análogos & derivados , Hypocreales/química , Tylenchoidea/efeitos dos fármacos , Animais , Antinematódeos/química , Cucumis sativus/parasitologia , Locomoção , Reprodução , Tylenchoidea/patogenicidade , Tylenchoidea/fisiologia
4.
Nat Commun ; 12(1): 4409, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285209

RESUMO

Appetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior-predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.


Assuntos
Comportamento Apetitivo/fisiologia , Locomoção/fisiologia , Parte Compacta da Substância Negra/fisiologia , Comportamento Predatório/fisiologia , Colículos Superiores/fisiologia , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Vias Neurais/fisiologia , Parte Compacta da Substância Negra/citologia , Técnicas Estereotáxicas , Colículos Superiores/citologia , Transmissão Sináptica/fisiologia
5.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202085

RESUMO

Neuronal circuits in the spinal cord are essential for the control of locomotion. They integrate supraspinal commands and afferent feedback signals to produce coordinated rhythmic muscle activations necessary for stable locomotion. For several decades, computational modeling has complemented experimental studies by providing a mechanistic rationale for experimental observations and by deriving experimentally testable predictions. This symbiotic relationship between experimental and computational approaches has resulted in numerous fundamental insights. With recent advances in molecular and genetic methods, it has become possible to manipulate specific constituent elements of the spinal circuitry and relate them to locomotor behavior. This has led to computational modeling studies investigating mechanisms at the level of genetically defined neuronal populations and their interactions. We review literature on the spinal locomotor circuitry from a computational perspective. By reviewing examples leading up to and in the age of molecular genetics, we demonstrate the importance of computational modeling and its interactions with experiments. Moving forward, neuromechanical models with neuronal circuitry modeled at the level of genetically defined neuronal populations will be required to further unravel the mechanisms by which neuronal interactions lead to locomotor behavior.


Assuntos
Estudos de Associação Genética , Locomoção , Modelos Neurológicos , Neurônios Motores/fisiologia , Medula Espinal/fisiologia , Animais , Retroalimentação Sensorial , Humanos , Interneurônios/fisiologia
6.
J Exp Biol ; 224(11)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34109985

RESUMO

Granular substrates ranging from silt to gravel cover much of the Earth's land area, providing an important habitat for fossorial animals. Many of these animals use their heads to penetrate the substrate. Although there is considerable variation in head shape, how head shape affects fossorial locomotor performance in different granular substrates is poorly understood. Here, head shape variation for 152 species of fossorial lizards was quantified for head diameter, slope and pointiness of the snout. The force needed to penetrate different substrates was measured using 28 physical models spanning this evolved variation. Ten substrates were considered, ranging in particle size from 0.025 to 4 mm in diameter and consisting of spherical or angular particles. Head shape evolved in a weakly correlated manner, with snouts that were gently sloped being blunter. There were also significant clade differences in head shape among fossorial lizards. Experiments with physical models showed that as head diameter increased, absolute penetration force increased but force normalized by cross-sectional area decreased. Penetration force decreased for snouts that tapered more gradually and were pointier. Larger and angular particles required higher penetration forces, although intermediate size spherical particles, consistent with coarse sand, required the lowest force. Particle size and head diameter effect were largest, indicating that fossorial burrowers should evolve narrow heads and bodies, and select relatively fine particles. However, variation in evolved head shapes and recorded penetration forces suggests that kinematics of fossorial movement are likely an important factor in explaining evolved diversity.


Assuntos
Lagartos , Animais , Ecossistema , Cabeça , Lagartos/anatomia & histologia , Locomoção , Tamanho da Partícula
7.
J Exp Biol ; 224(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34151369

RESUMO

Lateral undulation is the most widespread mode of terrestrial vertebrate limbless locomotion, in which posteriorly propagating horizontal waves press against environmental asperities (e.g. grass, rocks) and generate propulsive reaction forces. We hypothesized that snakes can generate propulsion using a similar mechanism of posteriorly propagating vertical waves pressing against suitably oriented environmental asperities. Using an array of horizontally oriented cylinders, one of which was equipped with force sensors, and a motion capture system, we found snakes generated substantial propulsive force and propulsive impulse with minimal contribution from lateral undulation. Additional tests showed that snakes could propel themselves via vertical undulations from a single suitable contact point, and this mechanism was replicated in a robotic model. Vertical undulations can provide snakes with a valuable locomotor tool for taking advantage of vertical asperities in a variety of habitats, potentially in combination with lateral undulation, to fully exploit the 3D structure of the habitat.


Assuntos
Robótica , Serpentes , Animais , Fenômenos Biomecânicos , Ecossistema , Locomoção
8.
J Biomech ; 123: 110527, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34077770

RESUMO

Human running can be simulated using a simple model called the spring-loaded inverted pendulum (SLIP). The SLIP model predicts some aspects of running including the self-stabilizing properties of running. In human locomotion energy is dissipated due to the passive motion of the soft tissue. However, little is known about the effects of this energy dissipation on the dynamics of running. This study utilizes a SLIP model with an additional spring-mass-damper system to study the effects of energy dissipation due to an additional wobbling mass on the self-stabilizing properties of human running. It was found that the additional spring-mass-damper system increased the self-stabilizing properties of the SLIP model and increased its robustness to perturbations. This suggests that increasing stability is one of the effects of energy dissipation due to the passive motion of a wobbling mass during human running.


Assuntos
Modelos Biológicos , Corrida , Fenômenos Biomecânicos , Humanos , Locomoção
9.
Artigo em Inglês | MEDLINE | ID: mdl-34070639

RESUMO

The purpose of this study was to quantify the exercise intensity and technical involvement of U9 boys' and girls' team handball during different game formats, and the differences between genders. Locomotor activity (total distance, distance in speed zones, accelerations, and decelerations), heart rate (HR), and technical involvement (shots, goals, and duels) metrics were collected during various 15 min game formats from a total of 57 Danish U9 players (37 boys and 20 girls). Game formats were a small size pitch (20 × 13 m) with 3 vs. 3 players and offensive goalkeepers (S3 + 1) and 4 vs. 4 players (S4), a medium size pitch (25.8 × 20 m) with 4 vs. 4 (M4) and 5 vs. 5 (M5) players, and a large size pitch (40 × 20 m) with 5 vs. 5 (L5) players. Boys and girls covered a higher total distance (TD) of high-speed running (HSR) and sprinting during L5 games compared to all other game formats (p < 0.05; ES = (-0.9 to -2.1), (-1.4 to -2.8), and (-0.9 to -1.3) respectively). Players covered the highest amount of sprinting distance in L5 games compared to all other game formats (p < 0.01; ES = 0.8 to 1.4). In all the game formats, players spent from 3.04 to 5.96 min in 180-200 bpm and 0.03 min to 0.85 min in >200 bpm of the total 15 min. In addition, both genders had more shots in S3 + 1 than M5 (p < 0.01; ES = 1.0 (0.4; 1.7)) and L5 (p < 0.01; ES = 1.1 (0.6; 2.2)). Team handball matches have high heart rates, total distances covered, and high-intensity running distances for U9 boys and girls irrespective of the game format. Locomotor demands appeared to be even higher when playing on larger pitches, whereas the smaller pitch size and fewer players led to elevated technical involvement.


Assuntos
Desempenho Atlético , Corrida , Aceleração , Feminino , Frequência Cardíaca , Humanos , Locomoção , Masculino
10.
Psychopharmacology (Berl) ; 238(7): 2043-2044, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34115156

RESUMO

With respect to Guo's inspiring article (Guo et al. 2021), we would like to suggest several corrections about some of the figures. We felt obliged to write this erratum letter as these incompatibilities may cause confusion for the readers.


Assuntos
Transtorno Depressivo Maior/metabolismo , Receptores sigma/metabolismo , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacologia , Animais , Ligantes , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos
11.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070932

RESUMO

The neuronal networks that generate locomotion are well understood in swimming animals such as the lamprey, zebrafish and tadpole. The networks controlling locomotion in tetrapods remain, however, still enigmatic with an intricate motor pattern required for the control of the entire limb during the support, lift off, and flexion phase, and most demandingly when the limb makes contact with ground again. It is clear that the inhibition that occurs between bursts in each step cycle is produced by V2b and V1 interneurons, and that a deletion of these interneurons leads to synchronous flexor-extensor bursting. The ability to generate rhythmic bursting is distributed over all segments comprising part of the central pattern generator network (CPG). It is unclear how the rhythmic bursting is generated; however, Shox2, V2a and HB9 interneurons do contribute. To deduce a possible organization of the locomotor CPG, simulations have been elaborated. The motor pattern has been simulated in considerable detail with a network composed of unit burst generators; one for each group of close synergistic muscle groups at each joint. This unit burst generator model can reproduce the complex burst pattern with a constant flexion phase and a shortened extensor phase as the speed increases. Moreover, the unit burst generator model is versatile and can generate both forward and backward locomotion.


Assuntos
Geradores de Padrão Central/fisiologia , Interneurônios/fisiologia , Locomoção/fisiologia , Atividade Motora/fisiologia , Redes Neurais de Computação , Medula Espinal/fisiologia , Animais , Gatos , Geradores de Padrão Central/citologia , Simulação por Computador , Extremidades/inervação , Extremidades/fisiologia , Humanos , Interneurônios/citologia , Lampreias/fisiologia , Larva/fisiologia , Neurônios Motores/citologia , Neurônios Motores/fisiologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Roedores/fisiologia , Medula Espinal/citologia , Peixe-Zebra/fisiologia
12.
Nutrients ; 13(5)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065946

RESUMO

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration. A lack of dystrophin in DMD leads to inflammatory response, autophagic dysregulation, and oxidative stress in skeletal muscle fibers that play a key role in the progression of the pathology. ß-glucans can modulate immune function by modifying the phagocytic activity of immunocompetent cells, notably macrophages. Mitochondrial function is also involved in an important mechanism of the innate and adaptive immune responses, owing to high need for energy of immune cells. In the present study, the effects of 1,3-1,6 ß-glucans on five-day-old non-dystrophic and dystrophic (sapje) zebrafish larvae were investigated. The effects of the sonication of ß-glucans and the dechorionation of embryos were also evaluated. The results showed that the incidence of dystrophic phenotypes was reduced when dystrophic embryos were exposed to 2 and 4 mg L-1 of 1,3-1,6 ß-glucans. Moreover, when the dystrophic larvae underwent 8 mg L-1 treatment, an improvement of the locomotor performances and mitochondrial respiration were observed. In conclusion, the observed results demonstrated that 1,3-1,6 ß-glucans improve locomotor performances and mitochondrial function in dystrophic zebrafish. Therefore, for ameliorating their life quality, 1,3-1,6 ß-glucans look like a promising diet supplement for DMD patients, even though further investigations are required.


Assuntos
Suplementos Nutricionais , Locomoção/efeitos dos fármacos , Mitocôndrias Musculares/efeitos dos fármacos , Distrofia Muscular de Duchenne/tratamento farmacológico , beta-Glucanas/uso terapêutico , Animais , Modelos Animais de Doenças , Larva , Mitocôndrias Musculares/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/fisiopatologia , Peixe-Zebra
13.
Neuroscience ; 466: 260-272, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34088581

RESUMO

Robust locomotion is critical to many species' survival, yet the mechanisms by which efficient locomotion is learned and maintained are poorly understood. In mice, a common paradigm for assaying locomotor learning is the rotarod task, in which mice learn to maintain balance atop of an accelerating rod. However, the standard metric for learning in this task is improvements in latency to fall, which gives little insight into the rich kinematic adjustments that accompany locomotor learning. In this study, we developed a rotarod-like task called the RotaWheel in which changes in paw kinematics are tracked using high-speed cameras as mice learn to stay atop an accelerating wheel. Using this device, we found that learning was accompanied by stereotyped progressions of paw kinematics that correlated with early, intermediate, and late stages of performance. Within the first day, mice sharpened their interlimb coordination using a timed pause in the forward swing of their forepaws. Over the next several days, mice reduced their stride length and took shorter, quicker steps. By the second week of training, mice began to use a more variable locomotor strategy, where consecutive overshoots or undershoots in strides were selected across paws to drive forward and backward exploration of the wheel. Collectively, our results suggest that mouse locomotor learning occurs through multiple mechanisms evolving over separate time courses and involving distinct corrective actions. These data provide insights into the kinematic strategies that accompany locomotor learning and establish an experimental platform for studying locomotor skill learning in mice.


Assuntos
Aprendizagem , Locomoção , Animais , Fenômenos Biomecânicos , Camundongos
14.
Artigo em Inglês | MEDLINE | ID: mdl-34097612

RESUMO

This paper focuses on the design and comparison of different deep neural networks for the real-time prediction of locomotor and transition intentions of one osseointegrated transfemoral amputee using only data from inertial measurement units. The deep neural networks are based on convolutional neural networks, recurrent neural networks, and convolutional recurrent neural networks. The architectures' input are features in both the time domain and the time-frequency domain, which are derived from either one inertial measurement unit (placed above the prosthetic knee) or two inertial measurement units (placed above and below the prosthetic knee). The prediction of eight different locomotion modes (i.e., sitting, standing, level ground walking, stair ascent and descent, ramp ascent and descent, walking on uneven terrain) and the twenty-four transitions among them is investigated. The study shows that a recurrent neural network, realized with four layers of gated recurrent unit networks, achieves (with a 5-fold cross-validation) a mean F1 score of 84.78% and 86.50% using one inertial measurement unit, and 93.06% and 89.99% using two inertial measurement units, with or without sitting, respectively.


Assuntos
Amputados , Humanos , Intenção , Locomoção , Redes Neurais de Computação , Caminhada
15.
Artigo em Inglês | MEDLINE | ID: mdl-34097615

RESUMO

Detecting human movement intentions is fundamental to neural control of robotic exoskeletons, as it is essential for achieving seamless transitions between different locomotion modes. In this study, we enhanced a muscle synergy-inspired method of locomotion mode identification by fusing the electromyography data with two types of data from wearable sensors (inertial measurement units), namely linear acceleration and angular velocity. From the finite state machine perspective, the enhanced method was used to systematically identify 2 static modes, 7 dynamic modes, and 27 transitions among them. In addition to the five broadly studied modes (level ground walking, ramps ascent/descent, stairs ascent/descent), we identified the transition between different walking speeds and modes of ramp walking at different inclination angles. Seven combinations of sensor fusion were conducted, on experimental data from 8 able-bodied adult subjects, and their classification accuracy and prediction time were compared. Prediction based on a fusion of electromyography and gyroscope (angular velocity) data predicted transitions earlier and with higher accuracy. All transitions and modes were identified with a total average classification accuracy of 94.5% with fused sensor data. For nearly all transitions, we were able to predict the next locomotion mode 300-500ms prior to the step into that mode.


Assuntos
Intenção , Dispositivos Eletrônicos Vestíveis , Adulto , Eletromiografia , Humanos , Locomoção , Músculos , Caminhada
16.
J Exp Biol ; 224(13): 1-7, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34142703

RESUMO

Manduca sexta larvae are an important model system for studying the neuromechanics of soft body locomotion. They climb on plants using the abdominal prolegs to grip and maneuver in any orientation and on different surfaces. The prolegs grip passively with an array of cuticular hooks, and grip release is actively controlled by retractor muscles inserted into the soft planta membrane at the proleg tip. Until now, the principal planta retractor muscles (PPRMs) in each body segment were thought to be a single fiber bundle originating on the lateral body wall. Here, using high resolution X-ray microtomography of intact animals, we show that the PPRM is a more complex muscle consisting of multiple contractile fibers originating at several distinct sites on the proleg. Furthermore, we show that there are segmental differences in the number and size of some of these fiber groups which suggests that the prolegs may operate differently along the anterior-posterior axis.


Assuntos
Manduca , Animais , Extremidades , Larva , Locomoção , Músculos
17.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064099

RESUMO

Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0-1.0 mg/kg) on alcohol drinking in both female and male mice from two genetically distinct C57BL/6 substrains. Under two different binge-drinking procedures, A33 pretreatment reduced alcohol intake in male and female mice of both substrains. In both drinking studies, there was no evidence for carry-over effects the next day; however, we did observe some sign of tolerance to A33's effect on alcohol intake upon repeated, intermittent, treatment (5 injections of 1.0 mg/kg, every other day). Pretreatment with 1.0 mg/kg of A33 augmented sucrose intake by C57BL/6NJ, but not C57BL/6J, mice. In mice with a prior history of A33 pretreatment during alcohol-drinking, A33 (1.0 mg/kg) did not alter spontaneous locomotor activity or basal motor coordination, nor did it alter alcohol's effects on motor activity, coordination or sedation. In a distinct cohort of alcohol-naïve mice, acute pretreatment with 1.0 mg/kg of A33 did not alter motor performance on a rotarod and reduced sensitivity to the acute intoxicating effects of alcohol. These data provide the first evidence that selective PDE4B inhibition is an effective strategy for reducing excessive alcohol intake in murine models of binge drinking, with minimal off-target effects. Despite reducing sensitivity to acute alcohol intoxication, PDE4B inhibition reduces binge alcohol drinking, without influencing behavioral sensitivity to alcohol in alcohol-experienced mice. Furthermore, A33 is equally effective in males and females and exerts a quantitatively similar reduction in alcohol intake in mice with a genetic predisposition for high versus moderate alcohol preference. Such findings further support the safety and potential clinical utility of targeting PDE4 for treating AUD.


Assuntos
Consumo Excessivo de Bebidas Alcoólicas/tratamento farmacológico , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Animais , Etanol/efeitos adversos , Feminino , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
Nat Commun ; 12(1): 3251, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059686

RESUMO

ALS is characterized by progressive inability to execute movements. Motor neurons innervating fast-twitch muscle-fibers preferentially degenerate. The reason for this differential vulnerability and its consequences on motor output is not known. Here, we uncover that fast motor neurons receive stronger inhibitory synaptic inputs than slow motor neurons, and disease progression in the SOD1G93A mouse model leads to specific loss of inhibitory synapses onto fast motor neurons. Inhibitory V1 interneurons show similar innervation pattern and loss of synapses. Moreover, from postnatal day 63, there is a loss of V1 interneurons in the SOD1G93A mouse. The V1 interneuron degeneration appears before motor neuron death and is paralleled by the development of a specific locomotor deficit affecting speed and limb coordination. This distinct ALS-induced locomotor deficit is phenocopied in wild-type mice but not in SOD1G93A mice after appearing of the locomotor phenotype when V1 spinal interneurons are silenced. Our study identifies a potential source of non-autonomous motor neuronal vulnerability in ALS and links ALS-induced changes in locomotor phenotype to inhibitory V1-interneurons.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Interneurônios/patologia , Locomoção/fisiologia , Neurônios Motores/patologia , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/patologia , Animais , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Fibras Musculares de Contração Rápida/fisiologia , Junção Neuromuscular/patologia , Junção Neuromuscular/fisiopatologia , Medula Espinal/citologia , Superóxido Dismutase/genética , Superóxido Dismutase-1/genética
19.
Sensors (Basel) ; 21(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070859

RESUMO

The protraction and retraction angles of horse limbs are important in the analysis of horse locomotion. This study explored two methods from an IMU positioned on the canon bone of eight horses to estimate these angles. Each method was based on a hypothesis in order to define the moment corresponding with the verticality of the canon bone: (i) the canon bone is in a vertical position at 50% of the stance phase or (ii) the verticality of the canon bone corresponds with the moment when the horse's withers reach their lowest point. The measurements were carried out on a treadmill at a trot and compared with a standard gold method based on motion capture. For the measurement of the maximum protraction and retraction angles, method (i) had average biases (0.7° and 1.7°) less than method (ii) (-1.3° and 3.7°). For the measurement of the protraction and retraction angles during the stance phase, method (i) had average biases (4.1° and -3.3°) higher to method (ii) (2.1° and -1.3°). This study investigated the pros and cons of a generic method (i) vs. a specific method (ii) to determine the protraction and retraction angles of horse limbs by a single IMU.


Assuntos
Marcha , Locomoção , Animais , Fenômenos Biomecânicos , Teste de Esforço , Cavalos , Tronco
20.
Sensors (Basel) ; 21(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071262

RESUMO

The inspection and maintenance of drains with varying heights necessitates a drain mapping robot with trained labour to maintain community hygiene and prevent the spread of diseases. For adapting to level changes and navigating in the narrow confined environments of drains, we developed a self-configurable hybrid robot, named Tarantula-II. The platform is a quadruped robot with hybrid locomotion and the ability to reconfigure to achieve variable height and width. It has four legs, and each leg is made of linear actuators and modular rolling wheel mechanisms with bi-directional movement. The platform has a fuzzy logic system for collision avoidance of the side wall in the drain environment. During level shifting, the platform achieves stability by using the pitch angle as the feedback from the inertial measuring unit (IMU) mounted on the platform. This feedback helps to adjust the accurate height of the platform. In this paper, we describe the detailed mechanical design and system architecture, kinematic models, control architecture, and stability of the platform. We deployed the platform both in a lab setting and in a real-time drain environment to demonstrate the wall collision avoidance, stability, and level shifting capabilities of the platform.


Assuntos
Robótica , Fenômenos Biomecânicos , Drenagem , Lógica Fuzzy , Locomoção
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