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1.
CNS Neurosci Ther ; 30(5): e14739, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38702935

RESUMEN

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.


Asunto(s)
Antipsicóticos , Aripiprazol , Modelos Animales de Enfermedad , Maleato de Dizocilpina , Hipocampo , Hipercinesia , Esquizofrenia , Animales , Aripiprazol/farmacología , Aripiprazol/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Maleato de Dizocilpina/farmacología , Ratones , Hipercinesia/tratamiento farmacológico , Masculino , Locomoción/efectos de los fármacos , Locomoción/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Ratones Endogámicos C57BL , Animales Recién Nacidos , Neuronas/efectos de los fármacos , Ritmo Teta/efectos de los fármacos , Ritmo Teta/fisiología
2.
Clinics (Sao Paulo) ; 79: 100359, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38657346

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the GSH effect on functional and histological recovery after experimental spinal cord injury in rats. METHODS: Forty Wistar rats were subjected to spinal cord injury through the Multicenter Animal Spinal Cord Injury Study (MASCIS) Impactor system. The rats were sorted and divided into four groups, as follows: Group 1 ‒ Laminectomy and spinal cord injury; Group 2 ‒ Laminectomy, spinal cord injury and Saline Solution (SS) 0.9%; Group 3 ‒ Laminectomy, spinal cord injury, and GSH; and Group 4 ‒ lLaminectomy without spinal cord injury. GSH and SS were administered intraperitoneally. Groups 1 and 4 received no intervention. RESULTS: The rats were evaluated for locomotor function recovery at seven different times by the Basso, Beattie, and Bresnahan (BBB) scale on days 2, 7, 14, 21, 28, 35, and 42 after the spinal cord injury. On day 42, the rats were sacrificed to analyze the histological findings of the injured spinal cord. In the group submitted to GSH, our experimental study revealed better functional scores on the BBB scale, horizontal ladder scale, and cranial and caudal axon count. The differences found were statistically significant in BBB scores and axonal count analysis. CONCLUSION: This study demonstrated that using glutathione in experimental spinal trauma can lead to better functional recovery and improved axonal regeneration rate in Wistar rats submitted to experimental spinal cord injury.


Asunto(s)
Modelos Animales de Enfermedad , Glutatión , Ratas Wistar , Recuperación de la Función , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/patología , Factores de Tiempo , Laminectomía , Masculino , Médula Espinal/patología , Médula Espinal/fisiopatología , Distribución Aleatoria , Ratas , Axones/patología , Locomoción/fisiología , Reproducibilidad de los Resultados , Actividad Motora/fisiología , Resultado del Tratamiento
3.
Elife ; 132024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591541

RESUMEN

Collective cell migration is fundamental for the development of organisms and in the adult for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact inhibition of locomotion (CIL), a local repulsive force, can propel the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell (SC) collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin is required to present the repulsive Slit2/Slit3 signal at the cell surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, nonmigratory cell clusters. Moreover, analysis of ex vivo explants from mice following sciatic nerve injury showed that inhibition of Slit2 decreased SC collective migration and increased clustering of SCs within the nerve bridge. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.


Asunto(s)
Cadherinas , Movimiento Celular , Inhibición de Contacto , Péptidos y Proteínas de Señalización Intercelular , Proteínas de la Membrana , Regeneración Nerviosa , Proteínas del Tejido Nervioso , Células de Schwann , Células de Schwann/metabolismo , Células de Schwann/fisiología , Animales , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Ratones , Cadherinas/metabolismo , Cadherinas/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Regeneración Nerviosa/fisiología , Locomoción/fisiología , Adhesión Celular , Transducción de Señal
4.
Neuropeptides ; 105: 102425, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38554699

RESUMEN

The control of feeding and physical activity is tightly linked and coordinated. However the underlying mechanisms are unclear. One of the major regulatory systems of feeding behaviour involves neuropeptide Y (NPY) signalling, with the signalling mediated through NPY Y4 receptor also known to influence activity. Here we show that mice globally lacking the Npy4r (Npy4r-/-) in the absence of access to a running wheel behaved WT-like with regards to food intake, energy expenditure, respiratory exchange ratio and locomotion regardless of being fed on a chow or high fat diet. Interestingly however, when given the access to a running wheel, Npy4r-/- mice while having a comparable locomotor activity, showed significantly higher wheel-running activity than WT, again regardless of dietary conditions. This higher wheel-running activity in Npy4r-/-mice arose from an increased dark-phase running time rather than changes in number of running bouts or the running speed. Consistently, energy expenditure was higher in Npy4r-/- than WT mice. Importantly, food intake was reduced in Npy4r-/-mice under wheel access condition which was due to decreased feeding bouts rather than changes in meal size. Together, these findings demonstrate an important role of Npy4r signalling in the dual control of feeding and physical activity, particularly in the form of wheel-running activity.


Asunto(s)
Ingestión de Alimentos , Metabolismo Energético , Conducta Alimentaria , Ratones Noqueados , Neuropéptido Y , Receptores de Neuropéptido Y , Transducción de Señal , Animales , Receptores de Neuropéptido Y/metabolismo , Receptores de Neuropéptido Y/genética , Transducción de Señal/fisiología , Neuropéptido Y/metabolismo , Metabolismo Energético/fisiología , Conducta Alimentaria/fisiología , Ingestión de Alimentos/fisiología , Ratones , Masculino , Ratones Endogámicos C57BL , Actividad Motora/fisiología , Condicionamiento Físico Animal/fisiología , Dieta Alta en Grasa , Locomoción/fisiología
5.
Soft Robot ; 11(1): 70-84, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37477672

RESUMEN

For decades, it has been difficult for small-scale legged robots to conquer challenging environments. To solve this problem, we propose the introduction of a bioinspired soft spine into a small-scale legged robot. By capturing the motion mechanism of rat erector spinae muscles and vertebrae, we designed a cable-driven centrally symmetric soft spine under limited volume and integrated it into our previous robotic rat SQuRo. We called this newly updated robot SQuRo-S. Because of the coupling compliant spine bending and leg locomotion, the environmental adaptability of SQuRo-S significantly improved. We conducted a series of experiments on challenging environments to verify the performance of SQuRo-S. The results demonstrated that SQuRo-S crossed an obstacle of 1.07 body height, thereby outperforming most small-scale legged robots. Remarkably, SQuRo-S traversed a narrow space of 0.86 body width. To the best of our knowledge, SQuRo-S is the first quadruped robot of this scale that is capable of traversing a narrow space with a width smaller than its own width. Moreover, SQuRo-S demonstrated stable walking on mud-sand, pipes, and slopes (20°), and resisted strong external impact and repositioned itself in various body postures. This work provides a new paradigm for enhancing the flexibility and adaptability of small-scale legged robots with spine in challenging environments, and can be easily generalized to the design and development of legged robots with spine of different scales.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Animales , Ratas , Locomoción/fisiología , Caminata , Columna Vertebral
6.
Artículo en Inglés | MEDLINE | ID: mdl-38083682

RESUMEN

Many small bionic crawling robots have been invented for search and rescue missions in narrow spaces. However, their locomotion capability is far from that of insects of the same size. Transforming a cockroach into a bio-bot has been a hot topic in the past decade. Herein, we modified this insect to perform surveillance work in dark confined environments. The synergistic electrical stimulation for turning control was proposed by alternating electrical stimulation of the cerci and antennae every 5 trials. The result showed that this method was able to control cockroaches turning steadily 117 times. An electronic backpack was designed, which was capable of transmitting images in real time, and a light emitting diode (LED) was installed on the backpack providing a light source for the camera. Thus, a vision-aided navigation system was formed for dark confined environments, e.g. pipelines. With a host computer software, the operator controlled the bio-bot to pass through a completely dark and closed pipeline. The electronic backpack and the host computer were connected via transmission control protocol (TCP), which allows the operator to manipulate the bio-robot remotely. This technology can be applied in pipeline surveillance in the future.


Asunto(s)
Cucarachas , Robótica , Caminata , Animales , Cucarachas/fisiología , Estimulación Eléctrica/métodos , Locomoción/fisiología , Robótica/métodos
7.
J Exp Biol ; 226(15)2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37565347

RESUMEN

Animal locomotion is the result of complex and multi-layered interactions between the nervous system, the musculo-skeletal system and the environment. Decoding the underlying mechanisms requires an integrative approach. Comparative experimental biology has allowed researchers to study the underlying components and some of their interactions across diverse animals. These studies have shown that locomotor neural circuits are distributed in the spinal cord, the midbrain and higher brain regions in vertebrates. The spinal cord plays a key role in locomotor control because it contains central pattern generators (CPGs) - systems of coupled neuronal oscillators that provide coordinated rhythmic control of muscle activation that can be viewed as feedforward controllers - and multiple reflex loops that provide feedback mechanisms. These circuits are activated and modulated by descending pathways from the brain. The relative contributions of CPGs, feedback loops and descending modulation, and how these vary between species and locomotor conditions, remain poorly understood. Robots and neuromechanical simulations can complement experimental approaches by testing specific hypotheses and performing what-if scenarios. This Review will give an overview of key knowledge gained from comparative vertebrate experiments, and insights obtained from neuromechanical simulations and robotic approaches. We suggest that the roles of CPGs, feedback loops and descending modulation vary among animals depending on body size, intrinsic mechanical stability, time required to reach locomotor maturity and speed effects. We also hypothesize that distal joints rely more on feedback control compared with proximal joints. Finally, we highlight important opportunities to address fundamental biological questions through continued collaboration between experimentalists and engineers.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Animales , Retroalimentación , Locomoción/fisiología , Médula Espinal/fisiología , Vertebrados
8.
BMJ Open ; 13(5): e068645, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37192799

RESUMEN

OBJECTIVES: The purpose of this study was to compile the currently available evidence on the clinical characteristics of the locomotive syndrome (LS) categorised by the 25-question Geriatric Locomotive Function Scale (GLFS-25) and clarify its clinical usefulness for assessing mobility function. DESIGN: Systematic review. DATA SOURCES: The PubMed and Google Scholar were searched for the relevant studies on 20 March 2022. ELIGIBILITY CRITERIA: We included relevant peer-reviewed articles, available in English language, on clinical LS characteristics categorised with the GLFS-25. DATA EXTRACTION AND SYNTHESIS: Pooled ORs or mean differences (MDs) of the LS groups were calculated and compared with the non-LS groups for each clinical characteristic. RESULTS: In total, 27 studies that involve 13 281 participants (LS, n=3385; non-LS, n=9896) were examined in this analysis. Older age (MD 4.71; 95% (CI) 3.97 to 5.44; p<0.00001), female gender (OR 1.54; 95% CI 1.38 to 1.71; p<0.00001), higher body mass index (MD 0.78; 95% CI 0.57 to 0.99; p<0.00001), osteoporosis (OR 1.68; 95% CI 1.32 to 2.13; p<0.0001), depression (OR 3.14; 95% CI 1.81 to 5.44; p<0.0001), lower lumbar lordosis angle (MD -7.91; 95% CI -10.08 to -5.74; p<0.00001), higher spinal inclination angle (MD 2.70; 95% CI 1.76 to 3.65; p<0.00001), lower grip strength (MD -4.04; 95% CI -5.25 to -2.83; p<0.00001), lower back muscle strength (MD -15.32; 95% CI -23.83 to -6.81; p=0.0004), lower maximum stride (MD -19.36; 95% CI -23.25 to -15.47; p<0.00001), higher timed up-and-go (MD 1.36; 95% CI 0.92 to 1.79; p<0.00001), lower one-leg standing time (MD -19.13; 95% CI -23.29 to -14.97; p<0.0001) and slower normal gait speed (MD -0.20; 95% CI -0.22 to -0.18; p<0.0001) were found to be associated with LS. No significant differences were noted in other clinical characteristics between the two groups. CONCLUSIONS: GLFS-25 is clinically useful for assessing mobility function according to the evidence available on the clinical characteristics of LS categorised by the GLFS-25 questionnaire items until.


Asunto(s)
Osteoporosis , Humanos , Femenino , Anciano , Fuerza de la Mano , Síndrome , Locomoción/fisiología , Encuestas y Cuestionarios
9.
J Exp Biol ; 226(9)2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37042272

RESUMEN

Control of locomotion involves the interplay of sensory signals and motor commands. Sensory information is essential for adjusting locomotion in response to environmental changes. A previous study using mathematical modelling of lamprey swimming has shown that, in the absence of sensory feedback, increasing fluid viscosity constrains swimming kinematics, limiting tail amplitude and body wavelength, resulting in decreased swimming speed. In contrast, previous experiments with Polypterus senegalus reported increased magnitude swimming kinematics (increased body curvature, body wave speed and frequency, and pectoral fin frequency) in high viscosity water suggesting that sensory information is used to adjust swimming form. It is not known what sensory systems are providing the necessary information to respond to these environmental changes. We tested the hypothesis that lateral line and visual input are responsible for the sensory-driven increase in swimming kinematics in response to experimentally increased fluid viscosity. The kinematics of five P. senegalus were recorded in two different viscosities of water while removing lateral line and visual sensory feedback. Unlike the mathematical model devoid of sensory feedback, P. senegalus with lateral line and/or visual senses removed did not reduce the magnitude of swimming kinematic variables, suggesting that additional sensory feedback mechanisms are present in these fish to help overcome increased fluid viscosity. Increases in swimming speed when both lateral line and visual sensory feedback were removed suggest that lateral line and visual information may be used to regulate swimming speed in P. senegalus, possibly using an internal model of predictions to adjust swimming form.


Asunto(s)
Privación Sensorial , Natación , Animales , Natación/fisiología , Locomoción/fisiología , Peces/fisiología , Fenómenos Biomecánicos/fisiología , Agua
10.
Zoology (Jena) ; 157: 126076, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36842298

RESUMEN

The evolutionary transformation of limb morphology to the four-segmented pantograph of therians is among the milestones of mammalian evolution. But, it is still unknown if changes of the mechanical limb function were accompanied by corresponding changes in development and sensorimotor control. The impressive locomotor performance of mammals leaves no doubt about the high integration of pattern formation, neural control and mechanics. But, deviations from normal intra- and interlimb coordination (spatial and temporal) become evident in the presence of perturbations. We induced a perturbation in the development of the neural circuits of the spinal cord of mice (Mus musculus) using a deletion of the Wilms tumor suppressor gene Wt1 in a subpopulation of dI6 interneurons. These interneurons are assumed to participate in the intermuscular coordination within the limb and in left-right-coordination between the limbs. We describe the locomotor kinematics in mice with conditional Wt1 knockout and compare them to mice without Wt1 deletion. Unlike knockout neonates, knockout adult mice do not display severe deviations from normal (=control group) interlimb coordination, but the coordinated protraction and retraction of the limbs is altered. The forelimbs are more affected by deviations from the control than the hindlimbs. This observation appears to reflect a different degree of integration and resistance against the induced perturbation between the limbs. Interestingly, the observed effects are similar to locomotor deficits reported to arise when sensory feedback from proprioceptors or cutaneous receptors is impaired. A putative participation of Wt1 positive dI6 interneurons in sensorimotor integration is therefore considered.


Asunto(s)
Locomoción , Médula Espinal , Animales , Ratones , Locomoción/fisiología , Fenómenos Biomecánicos , Miembro Posterior/fisiología , Médula Espinal/fisiología , Extremidades/fisiología , Mamíferos
11.
Sci Rep ; 13(1): 1571, 2023 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-36709355

RESUMEN

Robotic locomotion in subterranean environments is still unsolved, and it requires innovative designs and strategies to overcome the challenges of burrowing and moving in unstructured conditions with high pressure and friction at depths of a few centimeters. Inspired by antagonistic muscle contractions and constant volume coelomic chambers observed in earthworms, we designed and developed a modular soft robot based on a peristaltic soft actuator (PSA). The PSA demonstrates two active configurations from a neutral state by switching the input source between positive and negative pressure. PSA generates a longitudinal force for axial penetration and a radial force for anchorage, through bidirectional deformation of the central bellows-like structure, which demonstrates its versatility and ease of control. The performance of PSA depends on the amount and type of fluid confined in an elastomer chamber, generating different forces and displacements. The assembled robot with five PSA modules enabled to perform peristaltic locomotion in different media. The role of friction was also investigated during experimental locomotion tests by attaching passive scales like earthworm setae to the ventral side of the robot. This study proposes a new method for developing a peristaltic earthworm-like soft robot and provides a better understanding of locomotion in different environments.


Asunto(s)
Oligoquetos , Robótica , Animales , Oligoquetos/fisiología , Robótica/métodos , Locomoción/fisiología , Fricción , Peristaltismo/fisiología
12.
Mod Rheumatol ; 33(4): 836-842, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-35919937

RESUMEN

OBJECTIVES: This study aimed to evaluate preoperative and post-operative locomotive syndrome (LS) in older adults undergoing surgical treatment for musculoskeletal diseases of the lumbar spine and lower extremities and identify risk factors that impede LS improvement after surgery. METHODS: The baseline evaluation included 471 patients 65 years or older [276 in the pre-old-age (65-74 years) group; 195 in the old-age (75 years or older) group] and examined the preoperative and post-operative LS data. The second evaluation performed to identify risk factors, including anthropometric measurements, comorbidity, and frailty, that hinder LS improvement after surgery included 378 patients with preoperative LS Stage 3. RESULTS: Preoperatively, 80% of the patients had LS Stage 3; this rate decreased to 40% post-operatively. Half of the patients exhibited post-operative LS improvement. The LS improvement rate was higher in the pre-old-age group than in the old-age group. According to the multiple logistic regression analysis, old age, high body mass index, weak hand grip strength, and high 5-factor modified frailty index score were significant risk factors that hinder LS improvement after surgery. CONCLUSIONS: Ageing, obesity, weak muscle strength, and frailty can hinder LS improvement in older patients who undergo surgery.


Asunto(s)
Fragilidad , Enfermedades Musculoesqueléticas , Humanos , Anciano , Estudios Prospectivos , Fuerza de la Mano , Fragilidad/complicaciones , Fragilidad/diagnóstico , Fragilidad/cirugía , Locomoción/fisiología , Síndrome , Enfermedades Musculoesqueléticas/cirugía , Factores de Riesgo , Vértebras Lumbares
13.
Nature ; 611(7937): 762-768, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36352228

RESUMEN

The canonical model of striatal function predicts that animal locomotion is associated with the opposing regulation of protein kinase A (PKA) in direct and indirect pathway striatal spiny projection neurons (SPNs) by dopamine1-7. However, the precise dynamics of PKA in dorsolateral SPNs during locomotion remain to be determined. It is also unclear whether other neuromodulators are involved. Here we show that PKA activity in both types of SPNs is essential for normal locomotion. Using two-photon fluorescence lifetime imaging8-10 of a PKA sensor10 through gradient index lenses, we measured PKA activity within individual SPNs of the mouse dorsolateral striatum during locomotion. Consistent with the canonical view, dopamine activated PKA activity in direct pathway SPNs during locomotion through the dopamine D1 receptor. However, indirect pathway SPNs exhibited a greater increase in PKA activity, which was largely abolished through the blockade of adenosine A2A receptors. In agreement with these results, fibre photometry measurements of an adenosine sensor11 revealed an acute increase in extracellular adenosine during locomotion. Functionally, antagonism of dopamine or adenosine receptors resulted in distinct changes in SPN PKA activity, neuronal activity and locomotion. Together, our results suggest that acute adenosine accumulation interplays with dopamine release to orchestrate PKA activity in SPNs and proper striatal function during animal locomotion.


Asunto(s)
Adenosina , Cuerpo Estriado , Proteínas Quinasas Dependientes de AMP Cíclico , Dopamina , Locomoción , Neuronas , Animales , Ratones , Adenosina/metabolismo , Cuerpo Estriado/citología , Cuerpo Estriado/enzimología , Cuerpo Estriado/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Dopamina/metabolismo , Locomoción/fisiología , Neuronas/enzimología , Neuronas/metabolismo , Receptores de Dopamina D1/metabolismo , Receptor de Adenosina A2A/metabolismo
14.
Bioinspir Biomim ; 17(5)2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35700723

RESUMEN

While most insect-inspired robots come with a simple tarsus, such as a hemispherical foot tip, insect legs have complex tarsal structures and claws, which enable them to walk on complex terrain. Their sharp claws can smoothly attach and detach on plant surfaces by actuating a single muscle. Thus, installing an insect-inspired tarsus on legged robots would improve their locomotion on complex terrain. This paper shows that the tendon-driven ball-socket structure provides the tarsus with both flexibility and rigidity, which is necessary for the beetle to walk on a complex substrate such as a mesh surface. Disabling the tarsus' rigidity by removing the socket and elastic membrane of a tarsal joint, means that the claws could not attach to the mesh securely. Meanwhile, the beetle struggled to draw the claws out of the substrate when we turned the tarsus rigid by tubing. We then developed a cable-driven bio-inspired tarsus structure to validate the function of the tarsus as well as to show its potential application in the legged robot. With the tarsus, the robotic leg was able to attach and retract smoothly from the mesh substrate when performing a walking cycle.


Asunto(s)
Escarabajos , Procedimientos Quirúrgicos Robotizados , Robótica , Animales , Escarabajos/fisiología , Locomoción/fisiología , Extremidad Inferior/fisiología , Caminata
15.
Curr Biol ; 32(5): 1038-1048.e2, 2022 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-35104440

RESUMEN

Dynamic neuronal Na+/K+ pumps normally only respond to intense action potential firing owing to their low affinity for intracellular Na+. Recruitment of these Na+ pumps produces a post-activity ultraslow afterhyperpolarization (usAHP) up to ∼10 mV in amplitude and ∼60 s in duration, which influences neuronal properties and future network output. In spinal motor networks, the usAHP underlies short-term motor memory (STMM), reducing the intensity and duration of locomotor network output in a manner dependent on the interval between locomotor bouts. In contrast to tonically active Na+ pumps that help set and maintain the resting membrane potential, dynamic Na+ pumps are selectively antagonized by low concentrations of ouabain, which, we show, blocks both the usAHP and STMM. We examined whether dynamic Na+ pumps and STMM can be influenced by neuromodulators, focusing on 5-HT and nitric oxide. Bath-applied 5-HT alone had no significant effect on the usAHP or STMM. However, this is due to the simultaneous activation of two distinct 5-HT receptor subtypes (5-HT7 and 5-HT2a) that have opposing facilitatory and suppressive influences, respectively, on these two features of the locomotor system. Nitric oxide modulation exerts a potent inhibitory effect that can completely block the usAHP and erase STMM. Using selective blockers of 5-HT7 and 5-HT2a receptors and a nitric oxide scavenger, PTIO, we further provide evidence that the two modulators constitute an endogenous control system that determines how the spinal network self-regulates the intensity of locomotor output in light of recent past experience.


Asunto(s)
Óxido Nítrico , ATPasa Intercambiadora de Sodio-Potasio , Animales , Locomoción/fisiología , Serotonina , ATPasa Intercambiadora de Sodio-Potasio/farmacología , ATPasa Intercambiadora de Sodio-Potasio/fisiología , Médula Espinal/fisiología , Xenopus laevis/fisiología
16.
Behav Brain Res ; 417: 113630, 2022 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-34656691

RESUMEN

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.


Asunto(s)
Ansiedad/etiología , COVID-19 , Conducta Alimentaria , Hipocampo/metabolismo , Locomoción , Trastornos de la Memoria/etiología , Aislamiento Social , Factores de Edad , Animales , Conducta Animal/fisiología , Factor Neurotrófico Derivado del Encéfalo , COVID-19/prevención & control , Modelos Animales de Enfermedad , Conducta Alimentaria/fisiología , Vivienda para Animales , Hipotálamo/metabolismo , Locomoción/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-fos/metabolismo
17.
Cell Rep ; 37(8): 110019, 2021 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-34818559

RESUMEN

In cell transplantation therapy for spinal cord injury (SCI), grafted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) mainly differentiate into neurons, forming synapses in a process similar to neurodevelopment. In the developing nervous system, the activity of immature neurons has an important role in constructing and maintaining new synapses. Thus, we investigate how enhancing the activity of transplanted hiPSC-NS/PCs affects both the transplanted cells themselves and the host tissue. We find that chemogenetic stimulation of hiPSC-derived neural cells enhances cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhances the expression of synapse-related genes and proteins in surrounding host tissues and prevents atrophy of the injured spinal cord, thereby improving locomotor function. These findings provide a strategy for enhancing activity within the graft to improve the efficacy of cell transplantation therapy for SCI.


Asunto(s)
Células Madre Pluripotentes Inducidas/trasplante , Locomoción/fisiología , Traumatismos de la Médula Espinal/terapia , Animales , Diferenciación Celular/fisiología , Línea Celular , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/fisiología , Ratones , Ratones SCID , Células-Madre Neurales/metabolismo , Células-Madre Neurales/fisiología , Células-Madre Neurales/trasplante , Neuronas/metabolismo , Recuperación de la Función , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Trasplante de Células Madre/métodos
18.
PLoS One ; 16(11): e0252559, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34762669

RESUMEN

Syringomyelia (SM) is a spinal cord disorder in which a cyst (syrinx) filled with fluid forms in the spinal cord post-injury/disease, in patients syrinx symptoms include loss of pain and temperature sensation or locomotion deficit. Currently, there are no small animal models and connected tools to help study the functional impacts of SM. The objective of this study was to determine the detectability of subtle locomotion deficits due to syrinx formation/expansion in post-traumatic syringomyelia (PTSM) rat model using the recently reported method of Gait Analysis Instrumentation, and Technology Optimized for Rodents (GAITOR) with Automated Gait Analysis Through Hues and Areas (AGATHA) technique. First videos of the rats were collected while walking in an arena (using GAITOR) followed by extracting meaningful locomotion information from collected videos using AGATHA protocol. PTSM injured rats demonstrated detectable locomotion deficits in terms of duty factor imbalance, paw placement accuracy, step contact width, stride length, and phase dispersion parameters compared to uninjured rats due to SM. We concluded that this technique could detect mild and subtle locomotion deficits associated with PTSM injury, which also in future work could be used further to monitor locomotion responses after different treatment strategies for SM.


Asunto(s)
Hiperalgesia/fisiopatología , Locomoción/fisiología , Médula Espinal/fisiopatología , Siringomielia/fisiopatología , Caminata/fisiología , Animales , Modelos Animales de Enfermedad , Análisis de la Marcha , Masculino , Dimensión del Dolor , Ratas , Ratas Wistar
19.
Bioinspir Biomim ; 17(1)2021 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-34496355

RESUMEN

Earthworms (Lumbricus terrestris) are characterized by soft, highly flexible and extensible bodies, and are capable of locomoting in most terrestrial environments. Previous studies of earthworm movement focused on the use of retrograde peristaltic gaits in which controlled contraction of longitudinal and circular muscles results in waves of shortening/thickening and thinning/lengthening of the hydrostatic skeleton. These waves can propel the animal across ground as well as into soil. However, worms benefit from axial body bends during locomotion. Such lateral bending and buckling dynamics can aid locomotor function via hooking/anchoring (to provide propulsion), modify travel orientation (to avoid obstacles and generate turns) and even generate snake-like undulatory locomotion in environments where peristaltic locomotion results in poor performance. To the best of our knowledge, lateral bending and buckling of an earthworm's body has not yet been systematically investigated. In this study, we observed that within confined environments, worms use lateral bending and buckling to anchor their body to the walls of their burrows and tip (anterior end) bending to search the environment. This locomotion strategy improved the performance of our soft-bodied robophysical model of the earthworm both in a confined (in an acrylic tube) and above-ground heterogeneous environment (rigid pegs), where present peristaltic robots are relatively limited in terradynamic capabilities. In summary, lateral bending and buckling facilitates the mobility of earthworm locomotion in diverse terrain and can play an important role in the creation of low cost soft robotic devices capable of traversing a variety of environments.


Asunto(s)
Oligoquetos , Procedimientos Quirúrgicos Robotizados , Robótica , Animales , Marcha , Locomoción/fisiología , Oligoquetos/fisiología , Robótica/métodos
20.
Mol Neurobiol ; 58(11): 5494-5516, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34341881

RESUMEN

Spinal cord injury (SCI) is a devastating condition that affects approximately 294,000 people in the USA and several millions worldwide. The corticospinal motor circuitry plays a major role in controlling skilled movements and in planning and coordinating movements in mammals and can be damaged by SCI. While axonal regeneration of injured fibers over long distances is scarce in the adult CNS, substantial spontaneous neural reorganization and plasticity in the spared corticospinal motor circuitry has been shown in experimental SCI models, associated with functional recovery. Beneficially harnessing this neuroplasticity of the corticospinal motor circuitry represents a highly promising therapeutic approach for improving locomotor outcomes after SCI. Several different strategies have been used to date for this purpose including neuromodulation (spinal cord/brain stimulation strategies and brain-machine interfaces), rehabilitative training (targeting activity-dependent plasticity), stem cells and biological scaffolds, neuroregenerative/neuroprotective pharmacotherapies, and light-based therapies like photodynamic therapy (PDT) and photobiomodulation (PMBT). This review provides an overview of the spontaneous reorganization and neuroplasticity in the corticospinal motor circuitry after SCI and summarizes the various therapeutic approaches used to beneficially harness this neuroplasticity for functional recovery after SCI in preclinical animal model and clinical human patients' studies.


Asunto(s)
Plasticidad Neuronal , Tractos Piramidales/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Animales , Interfaces Cerebro-Computador , Terapia Combinada , Terapia por Estimulación Eléctrica , Humanos , Locomoción/fisiología , Terapia por Luz de Baja Intensidad , Corteza Motora/fisiopatología , Regeneración Nerviosa , Proyección Neuronal , Fármacos Neuroprotectores/uso terapéutico , Fotoquimioterapia , Calidad de Vida , Recuperación de la Función , Riluzol/uso terapéutico , Médula Espinal/fisiopatología , Enfermedades de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/terapia , Trasplante de Células Madre , Estimulación Transcraneal de Corriente Directa , Estimulación Eléctrica Transcutánea del Nervio
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