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1.
CNS Neurosci Ther ; 30(4): e14672, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38644561

RESUMEN

AIMS: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. METHODS: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. RESULTS: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. CONCLUSION: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Descanso , Convulsiones , Humanos , Masculino , Femenino , Adulto , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Descanso/fisiología , Adulto Joven , Convulsiones/fisiopatología , Convulsiones/diagnóstico por imagen , Persona de Mediana Edad , Mapeo Encefálico , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/farmacología , Adolescente , Actividad Motora/fisiología , Actividad Motora/efectos de los fármacos
2.
Cell Mol Neurobiol ; 44(1): 39, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649645

RESUMEN

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.


Asunto(s)
Proteínas Potenciadoras de Unión a CCAAT , Traumatismos de la Médula Espinal , Ubiquitina-Proteína Ligasas , Animales , Traumatismos de la Médula Espinal/fisiopatología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ratones , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Actividad Motora/fisiología , Ratones Endogámicos C57BL , Recuperación de la Función/fisiología , Femenino , Médula Espinal/metabolismo , Médula Espinal/patología , Regulación de la Expresión Génica
3.
Sci Rep ; 14(1): 5962, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472324

RESUMEN

Neuroscience heavily relies on animal welfare in laboratory rodents as it can significantly affect brain development, cognitive function and memory formation. Unfortunately, laboratory animals are often raised in artificial environments devoid of physical and social stimuli, potentially leading to biased outcomes in behavioural assays. To assess this effect, we examined the impact of social and physical cage enrichment on various forms of motor coordination. Our findings indicate that while enriched-housed animals did not exhibit faster learning in eyeblink conditioning, the peak timing of their conditioned responses was slightly, but significantly, improved. Additionally, enriched-housed animals outperformed animals that were housed in standard conditions in the accelerating rotarod and ErasmusLadder test. In contrast, we found no significant effect of enrichment on the balance beam and grip strength test. Overall, our data suggest that an enriched environment can improve motor performance and motor learning under challenging and/or novel circumstances, possibly reflecting an altered state of anxiety.


Asunto(s)
Ambiente , Actividad Motora , Ratones , Animales , Actividad Motora/fisiología , Aprendizaje , Animales de Laboratorio , Condicionamiento Clásico , Conducta Animal/fisiología , Aprendizaje por Laberinto/fisiología
4.
Mol Metab ; 82: 101907, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38428817

RESUMEN

OBJECTIVES: There is significant interest in uncovering the mechanisms through which exercise enhances cognition, memory, and mood, and lowers the risk of neurodegenerative diseases. In this study, we utilize forced treadmill running and distance-matched voluntary wheel running, coupled with light sheet 3D brain imaging and c-Fos immunohistochemistry, to generate a comprehensive atlas of exercise-induced brain activation in mice. METHODS: To investigate the effects of exercise on brain activity, we compared whole-brain activation profiles of mice subjected to treadmill running with mice subjected to distance-matched wheel running. Male mice were assigned to one of four groups: a) an acute bout of voluntary wheel running, b) confinement to a cage with a locked running wheel, c) forced treadmill running, or d) placement on an inactive treadmill. Immediately following each exercise or control intervention, blood samples were collected for plasma analysis, and brains were collected for whole-brain c-Fos quantification. RESULTS: Our dataset reveals 255 brain regions activated by acute exercise in mice, the majority of which have not previously been linked to exercise. We find a broad response of 140 regulated brain regions that are shared between voluntary wheel running and treadmill running, while 32 brain regions are uniquely regulated by wheel running and 83 brain regions uniquely regulated by treadmill running. In contrast to voluntary wheel running, forced treadmill running triggers activity in brain regions associated with stress, fear, and pain. CONCLUSIONS: Our findings demonstrate a significant overlap in neuronal activation signatures between voluntary wheel running and distance-matched forced treadmill running. However, our analysis also reveals notable differences and subtle nuances between these two widely used paradigms. The comprehensive dataset is accessible online at www.neuropedia.dk, with the aim of enabling future research directed towards unraveling the neurobiological response to exercise.


Asunto(s)
Actividad Motora , Condicionamiento Físico Animal , Ratones , Masculino , Animales , Actividad Motora/fisiología , Encéfalo , Cognición
5.
Commun Biol ; 7(1): 303, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461321

RESUMEN

Animal behavior emerges from integration of many processes with different spatial and temporal scales. Dynamical behavioral patterns, including daily and ultradian rhythms and the dynamical microstructure of behavior (i.e., autocorrelations properties), can be differentially affected by external cues. Identifying these patterns is important for understanding how organisms adapt to their environment, yet unbiased methods to quantify dynamical changes over multiple temporal scales are lacking. Herein, we combine a wavelet approach with Detrended Fluctuation Analysis to identify behavioral patterns and evaluate changes over 42-days in mice subjected to different dietary restriction paradigms. We show that feeding restriction alters dynamical patterns: not only are daily rhythms modulated but also the presence, phase and/or strength of ~12h-rhythms, as well as the nature of autocorrelation properties of feed-intake and wheel running behaviors. These results highlight the underlying complexity of behavioral architecture and offer insights into the multi-scale impact of feeding habits on physiology.


Asunto(s)
Ritmo Ultradiano , Ratones , Animales , Actividad Motora/fisiología , Conducta Animal/fisiología , Ingestión de Alimentos , Agricultura
6.
J Appl Physiol (1985) ; 136(3): 592-605, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38299221

RESUMEN

Regular exercise has numerous health benefits, but the human population displays significant variability in exercise participation. Rodent models, such as voluntary wheel running (VWR) in rats, can provide insight into the underlying mechanisms of exercise behavior and its regulation. In this study, we focused on the role of estrogen on VWR in female rats. Female rats run more than males, and we aimed to determine to what extent running levels in females were regulated by estrogen signaling. The running behavior of rats (duration, speed, and total distance run) was measured under normal physiological conditions, ovariectomy (OVX), and estrogen replacement in an OVX background. Results show cyclic variations in running linked to the estrous cycle. Ovariectomy markedly reduced running and eliminated the cyclic pattern. Estrogen replacement through estradiol benzoate (EB) injections and osmotic minipumps reinstated running activity to pre-OVX levels and restored the cyclic pattern. Importantly, individual differences and ranking are preserved such that high versus low runners before OVX remain high and low runners after treatment. Further analysis revealed that individual variation in running distance was primarily caused by rats running different speeds, but rats also varied in running duration. However, it is noteworthy that this model also displays features distinct from estrogen-driven running behavior under physiological conditions, notably a delayed onset and a broader duration of running activity. Collectively, this estrogen causality VWR model presents a unique opportunity to investigate sex-specific mechanisms that control voluntary physical activity.NEW & NOTEWORTHY This study investigates estrogen's role in voluntary wheel running (VWR) behavior in female rats. Female rats exhibit greater running than males, with estrogen signaling regulating this activity. The estrous cycle influences running, whereas ovariectomy reduces it, and estrogen replacement restores it, maintaining individual differences under all conditions. Both running speed and duration contribute to VWR variations. These findings emphasize individual estrogen regulation in female exercise and provide an estrogen replacement animal model for investigating neurobiological underpinnings that drive voluntary exercise behavior.


Asunto(s)
Individualidad , Actividad Motora , Masculino , Humanos , Ratas , Animales , Femenino , Actividad Motora/fisiología , Estrógenos/farmacología , Estradiol/farmacología , Ovariectomía
7.
BMC Public Health ; 24(1): 546, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383370

RESUMEN

BACKGROUND: The aim of our study was to determine how six mood indicators (vigour, fatigue, depression, anger, confusion, tension) depend on moderate to vigorous physical activity, walking time and sedentary time at work, after working hours and during leisure time, in men and women of different age groups. METHODS: A total of 1,140 individuals aged 18 to 64 years participated in the study. The participants were enrolled in this cross-sectional survey using a snowball sampling method. An online questionnaire was shared through popular social networks and emails within the period October 2019 to June 2020. Mood responses were assessed using The Brunel Mood Scale-LTU. Physical activity was assessed using the long International Physical Activity Questionnaire. Descriptive analysis, a two-way analysis of variance, and linear regression analysis were used to interpret the data. RESULTS: The survey results showed that vigour and fatigue correlated significantly only with leisure-time moderate to vigorous physical activity. The present results show a significant positive correlation between women and men moods and leisure-time moderate to vigorous physical activity, the length of time walking to work and back home, and negative correlation between moods and leisure-time sedentary behaviour. However, there was no significant correlation between moods and work-related moderate to vigorous physical activity and household moderate to vigorous physical activity, walking at work, and sitting duration at work. CONCLUSIONS: This study provides theoretical implications of the physical activity paradox, justifying the benefits of moderate to vigorous physical activity practiced in different circumstances. According to the regression analysis, exercising men in all age groups moved the most (had a higher moderate to vigorous physical activity level) during leisure time, the highest work-related moderate to vigorous physical activity was observed in men and women with lower education, and the highest household moderate to vigorous physical activity was observed in older age men and women living in rural areas. Clinicians and leaders at all levels of health care should consider the greater importance of leisure-time physical activity for mental health when choosing the most targeted physical activity recommendations for mood profile improvement in men and women of different age groups.


Asunto(s)
Actividades Recreativas , Actividad Motora , Masculino , Humanos , Femenino , Estudios Transversales , Actividad Motora/fisiología , Actividades Recreativas/psicología , Ejercicio Físico/fisiología , Fatiga
8.
Brain Struct Funct ; 229(2): 323-348, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38170266

RESUMEN

Anorexia nervosa (AN) is a mental illness with high rates of mortality and relapse, and no approved pharmacotherapy. Using the activity-based anorexia (ABA) model of AN, we previously showed that a single sub-anesthetic intraperitoneal injection of ketamine (30 mg/kg-KET, but not 3 mg/kg-KET), has an immediate and long-lasting effect of reducing anorexia-like behavior among adolescent female mice. We also showed previously that excitatory outflow from medial prefrontal cortex (mPFC) engages hunger-evoked hyperactivity, leading to the ABA condition of severe weight loss. Ketamine is known to target GluN2B-containing NMDARs (NR2B). Might synaptic plasticity involving NR2B in mPFC contribute to ketamine's ameliorative effects? We addressed this question through electron microscopic immunocytochemical quantification of GluN2B at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (IN) in mPFC layer 1 of animals that underwent recovery from a second ABA induction (ABA2), 22 days after ketamine injection during the first ABA induction. The 30 mg/kg-KET evoked synaptic plasticity that differed for PN and IN, with changes revolving the cytoplasmic reserve pool of NR2B more than the postsynaptic membrane pool. Those individuals that suppressed hunger-evoked wheel running the most and increased food consumption during recovery from ABA2 the most showed the greatest increase of NR2B at PN and IN excitatory synapses. We hypothesize that 30 mg/kg-KET promotes long-lasting changes in the reserve cytoplasmic pool of NR2B that enables activity-dependent rapid strengthening of mPFC circuits underlying the more adaptive behavior of suppressed running and enhanced food consumption, in turn supporting better weight restoration.


Asunto(s)
Ketamina , Ratones , Animales , Femenino , Ketamina/farmacología , Anorexia/tratamiento farmacológico , Receptores de N-Metil-D-Aspartato/metabolismo , Actividad Motora/fisiología , Células Piramidales/metabolismo , Interneuronas/metabolismo , Corteza Prefrontal/metabolismo
9.
Sci Rep ; 14(1): 146, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168503

RESUMEN

Circadian rhythms play a crucial role in the regulation of various physiological processes, including cardiovascular function and metabolism. Exercise provokes numerous beneficial adaptations in heart, including physiological hypertrophy, and serves to shift circadian rhythms. This study investigated the impact of time-restricted exercise training on exercise-induced adaptations in the heart and locomotor activity rhythms. Male mice (n = 45) were allocated to perform voluntary, time-restricted exercise in the early active phase (EAP), late active phase (LAP), or remain sedentary (SED) for 6 weeks. Subsequently, mice were allowed 24-h ad libitum access to the running wheel to assess diurnal rhythms in locomotor activity. Heart weight and cross-sectional area were measured at sacrifice, and cardiac protein and gene expression levels were assessed for markers of mitochondrial abundance and circadian clock gene expression. Mice rapidly adapted to wheel running, with EAP mice exhibiting a significantly greater running distance compared to LAP mice. Time-restricted exercise induced a shift in voluntary wheel activity during the 24-h free access period, with the acrophase in activity being significantly earlier in EAP mice compared to LAP mice. Gene expression analysis revealed a higher expression of Per1 in LAP mice. EAP exercise elicited greater cardiac hypertrophy compared to LAP exercise. These findings suggest that the timing of exercise affects myocardial adaptations, with exercise in the early active phase inducing hypertrophy in the heart. Understanding the time-of-day dependent response to exercise in the heart may have implications for optimizing exercise interventions for cardiovascular health.


Asunto(s)
Relojes Circadianos , Condicionamiento Físico Animal , Ratones , Masculino , Animales , Actividad Motora/fisiología , Ritmo Circadiano/fisiología , Condicionamiento Físico Animal/fisiología , Hipertrofia
10.
Med Sci Sports Exerc ; 56(3): 486-498, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37882083

RESUMEN

PURPOSE: The purpose of this study was to determine how the intersection of coactivator-associated arginine methyltransferase 1 (CARM1) and biological sex affects skeletal muscle adaptations to chronic physical activity. METHODS: Twelve-week-old female (F) and male (M) wild-type (WT) and CARM1 skeletal muscle-specific knockout (mKO) mice were randomly assigned to sedentary (SED) or voluntary wheel running (VWR) experimental groups. For 8 wk, the animals in the VWR cohort had volitional access to running wheels. Subsequently, we performed whole-body functional tests, and 48 h later muscles were harvested for molecular analysis. Western blotting, enzyme activity assays, as well as confocal and transmission electron microscopy were used to examine skeletal muscle biology. RESULTS: Our data reveal a sex-dependent reduction in VWR volume caused by muscle-specific ablation of CARM1, as F CARM1 mKO mice performed less chronic, volitional exercise than their WT counterparts. Regardless of VWR output, exercise-induced adaptations in physiological function were similar between experimental groups. A broad panel of protein arginine methyltransferase (PRMT) biology measurements, including markers of arginine methyltransferase expression and activity, were unaffected by VWR, except for CARM1 and PRMT7 protein levels, which decreased and increased with VWR, respectively. Changes in myofiber morphology and mitochondrial protein content showed similar trends among animals. However, a closer examination of transmission electron microscopy images revealed contrasting responses to VWR in CARM1 mKO mice compared with WT littermates, particularly in mitochondrial size and fractional area. CONCLUSIONS: The present findings demonstrate that CARM1 mKO reduces daily running volume in F mice, as well as exercise-evoked skeletal muscle mitochondrial plasticity, which indicates that this enzyme plays an essential role in sex-dependent differences in exercise performance and mitochondrial health.


Asunto(s)
Condicionamiento Físico Animal , Proteína-Arginina N-Metiltransferasas , Humanos , Masculino , Femenino , Ratones , Animales , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Actividad Motora/fisiología , Condicionamiento Físico Animal/fisiología , Músculo Esquelético/metabolismo , Ratones Endogámicos C57BL
11.
J Appl Physiol (1985) ; 136(1): 89-108, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37969082

RESUMEN

We present the first demonstration of chronic in vivo imaging of microglia in mice undergoing voluntary wheel running. We find that healthy mice undergoing voluntary wheel running have similar microglia dynamics, morphologies, and responses to injury when compared to sedentary mice. This suggests that exercise over a period of 1 mo does not grossly alter cortical microglial phenotypes and that exercise may exert its beneficial effects on the brain through other mechanisms. Future work examining how microglia dynamics may be altered during exercise in disease or injury models could provide further insights into the therapeutic benefit of exercise.NEW & NOTEWORTHY We demonstrate the first use of chronic in vivo imaging of microglia over time during physical exercise. We found that microglia movement, morphology, and process motility were remarkably stable during voluntary wheel running (VWR). Additionally, microglia in running mice respond similarly to laser ablation injury compared to sedentary mice. These findings indicate that VWR does not induce changes in microglia dynamics in healthy adults. Exercise may elicit positive effects on the brain through other mechanisms.


Asunto(s)
Microglía , Condicionamiento Físico Animal , Humanos , Ratones , Animales , Actividad Motora/fisiología , Condicionamiento Físico Animal/fisiología , Encéfalo
12.
Exp Physiol ; 109(2): 271-282, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37974360

RESUMEN

Murine exercise models are developed to study the molecular and cellular mechanisms regulating muscle mass. A progressive weighted wheel running model, named 'PoWeR', was previously developed to serve as a more translatable alternative to involuntary resistance-type exercise models in rodents, such as synergist ablation. However, mice still run great distances despite the added resistance as evidenced by a large glycolytic-to-oxidative shift in muscle fibre type. Thus, PoWeR reflects a blended resistance/endurance model. In an attempt to bias PoWeR further towards resistance-type exercise, we developed a novel heavy PoWeR model (hPoWeR) utilizing higher wheel loads (max of 12.5 g vs 6 g). Adult male C57BL/6 mice voluntarily performed an 8-week progressive loading protocol (PoWeR or hPoWeR). Running distance peaked at ∼5-6 km day-1 in both treatments and was maintained by PoWeR mice, but declined in the hPoWeR mice as load increased beyond 7.5 g. Peak isometric force of the gastrocnemius-soleus-plantaris complex tended to increase in wheel running treatments. Soleus mass increased by 19% and 24% in PoWeR and hPoWeR treatments, respectively, and plantaris fibre cross-sectional area was greater in hPoWeR, compared to PoWeR. There were fewer glycolytic and more oxidative fibres in the soleus and plantaris muscles in the PoWeR treatment, but not hPoWeR. Collectively, these data suggest hPoWeR may modestly alter skeletal muscle supporting the aim of better reflecting typical resistance training adaptations, in line with decreased running volume and exposure to higher resistance. Regardless, PoWeR remains an effective hypertrophic concurrent training model in mice.


Asunto(s)
Condicionamiento Físico Animal , Entrenamiento de Fuerza , Ratones , Masculino , Animales , Humanos , Actividad Motora/fisiología , Ratones Endogámicos C57BL , Músculo Esquelético/fisiología , Fibras Musculares Esqueléticas/fisiología , Condicionamiento Físico Animal/fisiología
13.
Dev Psychobiol ; 66(1): e22444, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38131238

RESUMEN

Exercise is known to promote efficient function of stress circuitry. The developing brain is malleable and thus exercise during adolescence could potentially exert lasting beneficial effects on the stress response that would be detectable in adulthood. The current study determined whether adolescent wheel running was associated with reduced stress response in adulthood, 6 weeks after cessation of exercise. Male and female adolescent rats voluntarily ran for 6 weeks and then were sedentary for 6 weeks prior to 10 days of chronic restraint stress in adulthood. Fecal corticosterone levels were measured during stress, and escape from the restraint tube was assessed on the final day as a proxy for depressive-like behavior. Anxiety-like behavior was measured 24 h later with the elevated plus maze and locomotor behaviors with the open field. Brain and body measurements were taken immediately following behavioral testing. Developmental exercise and adulthood stress both exerted independent effects on physiological and behavioral outcomes in adulthood. Exercise history increased the odds ratio of escape from restraint stress in males, but did not influence other stress-induced behaviors. In summary, exercise early in life exerted lasting effects, but did not substantially alter the adulthood response to restraint stress.


Asunto(s)
Actividad Motora , Restricción Física , Ratas , Masculino , Femenino , Animales , Actividad Motora/fisiología , Ansiedad , Corticosterona , Encéfalo , Estrés Psicológico
14.
Behav Brain Res ; 460: 114812, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38104637

RESUMEN

Numerous studies have shown that prior visual experiences play an important role in sensory processing and adapting behavior in a dynamic environment. A repeated and passive presentation of visual stimulus is one of the simplest procedures to manipulate acquired experiences. Using this approach, we aimed to investigate exposure-based visual learning of aging zebrafish and how cholinergic intervention is involved in exposure-induced changes. Our measurements included younger and older wild-type zebrafish and achesb55/+ mutants with decreased acetylcholinesterase activity. We examined both within-session and across-day changes in the zebrafish optomotor responses to repeated and passive exposure to visual motion. Our findings revealed short-term (within-session) changes in the magnitude of optomotor response (i.e., the amount of position shift by fish as a response to visual motion) rather than long-term and persistent effects across days. Moreover, the observed short-term changes were age- and genotype-dependent. Compared to the initial presentations of motion within a session, the magnitude of optomotor response to terminal presentations decreased in the older zebrafish. There was a similar robust decrease specific to achesb55/+ mutants. Taken together, these results point to short-term (within-session) alterations in the motion detection of adult zebrafish and suggest differential effects of neural aging and cholinergic system on the observed changes. These findings further provide important insights into adult zebrafish optomotor response to visual motion and contribute to understanding this reflexive behavior in the short- and long-term stimulation profiles.


Asunto(s)
Acetilcolinesterasa , Pez Cebra , Animales , Pez Cebra/fisiología , Actividad Motora/fisiología , Envejecimiento , Colinérgicos
15.
Brain Behav Immun ; 115: 419-431, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37924957

RESUMEN

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor CD59. The levels of upstream complement components (C3) and their inhibitors (CD55, CR1 and CFH) were altered by CCI, but not increased by voluntary wheel running. Since MAC can degrade myelin, which in turn contributes to neuropathic pain, we evaluated myelin integrity at the sciatic nerve injury site. We found that the loss of myelinated fibers and decreased myelin protein which occurs in sedentary rats following CCI was not observed in rats with prior running. Substitution of prior voluntary wheel running with exogenous CD59 also attenuated mechanical allodynia and reduced MAC deposition at the nerve injury site, pointing to CD59 as a critical effector of the neuroprotective and antinociceptive actions of prior voluntary wheel running. This study links attenuation of neuropathic pain by prior voluntary wheel running with inhibition of MAC and preservation of myelin integrity at the sciatic nerve injury site.


Asunto(s)
Neuralgia , Traumatismos de los Nervios Periféricos , Neuropatía Ciática , Humanos , Ratas , Animales , Vaina de Mielina/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento , Actividad Motora/fisiología , Traumatismos de los Nervios Periféricos/complicaciones , Hiperalgesia/metabolismo , Neuralgia/complicaciones , Nervio Ciático/lesiones
16.
PLoS One ; 18(12): e0293415, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38055657

RESUMEN

Regular physical activity is a proven routine for weight management in addressing obesity. Another method that has gained attention for its health benefits is intermittent fasting (IF). Physical and cognitive abilities while on these routines are poorly understood in the obese population. Sixty-five male Sprague Dawley rats at 7 weeks of age were subjected to diet-induced obesity by feeding a high-fat diet (HFD) or a standard diet (SD) for 8 weeks, after which behavioral testing was performed to detect any changes in physical and cognitive abilities. Rats from the HFD-fed (now considered obese) and SD-fed groups were then subjected to IF (18-hour fast and 6-hour feeding daily), voluntary wheel running (VWR), or control conditions for 3 weeks before repeating the same behavioral testing protocol. IF resulted in less weight gain (p<0.05) and elevated ketone levels (p<0.05) in both SD and HFD-fed groups. IF improved physical activity when compared to VWR and control animals in both SD and HFD-fed groups (p<0.05) while the VWR group in the SD-fed rats exhibited less physical fatigue compared to IF and controls (p<0.05). Additionally, elevated ketone levels were weakly correlated with decreased physical (p<0.0001) and exploratory behavior (p<0.01). These results suggest that IF is more effective than VWR in HFD and SD-fed rats in minimizing weight gain and retaining physical activity, and ketones may play a part in establishing the reported physical benefits. Exploration of physiological mechanisms between ketones, diet, and exercise will help fight obesity and many associated diseases.


Asunto(s)
Dieta Alta en Grasa , Ayuno Intermitente , Ratas , Masculino , Animales , Dieta Alta en Grasa/efectos adversos , Ratas Sprague-Dawley , Actividad Motora/fisiología , Obesidad/etiología , Aumento de Peso/fisiología , Cognición , Cetonas
17.
Behav Processes ; 213: 104973, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38013137

RESUMEN

Locomotor play is vigorous and seemingly purposeless behavior, commonly observed in young mammals. It can be costly in terms of energy expenditure, increased injury risk, and predator exposure. The main hypothesized benefit of locomotor play is enhancement of neuromuscular development, with effects persisting into adulthood. We hypothesized that levels of locomotor play would have evolved as a correlated response to artificial selection for increased voluntary exercise behavior. We studied mice from 4 replicate lines bred for voluntary wheel running (High Runner or HR) at 6-8 weeks of age and four non-selected Control (C) lines. Mice were weaned at 21 days of age and play behavior was observed for generations 20 (22-24 days old), 68 (22-23 days old), and 93 (15 days old). We quantified locomotor play as (1) rapid, horizontally directed jerk-run sequences and (2) vertical "bouncing." We used focal sampling to continuously record behavior in cages containing 4-6 individuals during the first 2-3 h of the dark cycle. Observations were significantly repeatable between observers and days. A two-way, mixed-model simultaneously tested effects of linetype (HR vs. C), sex, and their interaction. Contrary to our hypothesis, HR and C lines did not differ in any generation, nor did we find sex differences. However, differences among the replicate HR lines and among the replicate C lines were detected, and may be attributed to the effects of random genetic drift (and possibly founder effects). Thus, play behavior did evolve in this selection experiment, but not as a correlated response to selection for voluntary exercise.


Asunto(s)
Actividad Motora , Selección Artificial , Ratones , Femenino , Animales , Masculino , Actividad Motora/fisiología , Flujo Genético , Destete , Caracteres Sexuales , Selección Genética , Mamíferos
18.
J Vis Exp ; (200)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37929955

RESUMEN

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of AS. We use the rotarod learning paradigm, detailed gait analysis, and nest building test to detect and characterize animal motor impairments. We test animal emotionality in the open field and elevated plus maze tests, as well as the affect in the tail suspension test. When AS mice are tested in the open field test, the results should be interpreted with care, since motor dysfunctions influence mouse behavior in the maze and alter activity scores. The reproducibility and effectiveness of the presented behavioral tests has already been validated in several independent Uba3a mouse lines with different knockout variants, establishing this set of tests as an excellent validation tool in AS research. Models with the relevant construct and face validity will warrant further investigations to elucidate the pathophysiology of the disease and grant the development of causal treatments.


Asunto(s)
Síndrome de Angelman , Ratones , Animales , Síndrome de Angelman/genética , Modelos Animales de Enfermedad , Reproducibilidad de los Resultados , Aprendizaje , Actividad Motora/fisiología , Conducta Animal/fisiología , Aprendizaje por Laberinto
19.
Bull Exp Biol Med ; 175(5): 685-689, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37861898

RESUMEN

The multi-day dynamics of the intensity of 40K decay fluctuations was compared with motor activity of laboratory mice, circulating cortisol in rabbits, and proliferation of fibroblast-like cultured cells L-929. A positive correlation was established between the intensity of decay fluctuations on the one hand, and total daily motor activity in mice and plasma cortisol level in rabbits, on the other hand. In addition, a negative correlation was observed between 40K decay fluctuations and proliferative activity of the cultured cells. Interestingly, these close correlations were observed not only against the background 4-day rhythm, but also in the time when any rhythmicity was absent. Thus, the intensity of 40K decay fluctuations is an indicator of a biotropic environmental factor that augments motor activity and raises the circulating cortisol in animals and down-regulates proliferation of cultured cells.


Asunto(s)
Ritmo Circadiano , Ritmo Infradiano , Ratones , Conejos , Animales , Ritmo Circadiano/fisiología , Hidrocortisona , Proliferación Celular , Actividad Motora/fisiología
20.
Pediatr Phys Ther ; 35(4): 479-484, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37747985

RESUMEN

PURPOSE: The purpose of this study was to investigate the Head Control Scale's (HCS's) responsiveness and concurrent validity with the Alberta Infant Motor Scale (AIMS). METHODS: The HCS and the AIMS were administered to 50 infants and young children. Thirty children were reevaluated at hospital discharge or at 18 months of age. RESULTS: A statistically significant positive change was noted in mean score from the initial HCS assessment to the second assessment for total score and all position scores. Concurrent validity between HCS and AIMS total scores was excellent. CONCLUSION: Responsiveness to changes in head control and concurrent validity with the AIMS were established, supporting HCS use in clinical practice.


Asunto(s)
Desarrollo Infantil , Cabeza , Actividad Motora , Preescolar , Humanos , Lactante , Actividad Motora/fisiología , Examen Físico
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