RESUMEN
BACKGROUND: Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels. RESULTS: Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 - 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01-0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 - 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 - 0.01) and upregulated cerebral BDNF expression (p < 0.05). CONCLUSION: In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.
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Fibronectinas , Trastornos de la Memoria , Pentilenotetrazol , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Convulsiones , Animales , Masculino , Trastornos de la Memoria/etiología , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Fibronectinas/metabolismo , Fibronectinas/administración & dosificación , Ratas , Enfermedades Neuroinflamatorias , Epilepsia , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiologíaRESUMEN
This study aimed to evaluate the influence of combined intermittent fasting (IF) and high-intensity interval training (HIIT) on morphology, caspase-independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty-day-old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high-intensity-interval training (T), and high-intensity-interval training and intermittent fasting (T-IF). The C and T groups received ad libitum chow daily; IF and T-IF received the same standard chow every other day. Animals from T and T-IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro-apoptotic proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved-to-non-cleaved PARP-1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved-to-total PARP-1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross-sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved-to-non-cleaved PARP-1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase-independent apoptosis signaling.
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Factor Inductor de la Apoptosis , Apoptosis , Ayuno , Entrenamiento de Intervalos de Alta Intensidad , Fibras Musculares de Contracción Lenta , Atrofia Muscular , Miostatina , Ratas Wistar , Transducción de Señal , Animales , Masculino , Apoptosis/fisiología , Ayuno/metabolismo , Ayuno/fisiología , Miostatina/metabolismo , Entrenamiento de Intervalos de Alta Intensidad/métodos , Ratas , Transducción de Señal/fisiología , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Factor Inductor de la Apoptosis/metabolismo , Fibras Musculares de Contracción Lenta/metabolismo , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares de Contracción Rápida/patología , Endodesoxirribonucleasas/metabolismo , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Músculo Esquelético/metabolismo , Ayuno Intermitente , Poli(ADP-Ribosa) Polimerasa-1RESUMEN
BACKGROUND: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. METHODS: db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. RESULTS: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. CONCLUSIONS: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.
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Diferenciación Celular , Diabetes Mellitus Experimental , Interleucina-17 , Condicionamiento Físico Animal , Factor de Transcripción STAT3 , Células Th17 , Vasodilatación , Animales , Ratones , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Vasodilatación/fisiología , Factor de Transcripción STAT3/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Experimental/terapia , Masculino , Interleucina-17/sangre , Interleucina-17/metabolismo , Endotelio Vascular/fisiopatología , Resistencia a la Insulina/fisiología , Transducción de Señal , Ratones Endogámicos C57BL , Aorta/fisiopatologíaRESUMEN
To investigate the role of JAK2/STAT3 signaling pathway in neural function recovery in rats with spinal cord injury (SCI) after treadmill training. Sprague-Dawley rats were randomly divided into four groups: (a) sham group; (b) SCI group; (c) SCI+treadmill training group (SCI/TT); and (d) SCI/TT+AG490 group (a JAK2 inhibitor) ( n â =â 12). The 12 Sprague-Dawley rats in each group were randomly assigned into 1 st , 3 rd , 7 th , and 14 th â day subgroups. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to assess the spinal cord function, and JAK2, STAT3, and IL-6 protein expressions in the rat spinal cord were evaluated by western blot. The level of cell apoptosis and expressions of apoptotic proteins were evaluated by TUNEL assay and immunohistochemistry, respectively. Rats in the SCI+TT group showed a significantly higher BBB score after SCI compared with the SCI group and the SCI/TT+AG490 group. Mechanistically, the JAK2/STAT3 signal pathway was immediately activated after SCI compared with sham group, and JAK2 and STAT3 were obviously upregulated when treadmill training was performed ( P â <â 0.05). Results of TUNEL assay showed that the apoptotic rate in SCI/TT was significantly lower than that in the SCI group and SCI/TT+AG490 group ( P â <â 0.05). Besides, the IL-6 expression in the SCI/TT group was significantly attenuated compared with the SCI group ( P â <â 0.05). Our results showed that physical treadmill training can enhance activation of JAK2/STAT3 signal pathway and attenuate apoptosis in the injured spinal cord, resulting in better functional recovery. These results underline the importance of synergistic treatment strategies for SCI.
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Apoptosis , Janus Quinasa 2 , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Recuperación de la Función , Factor de Transcripción STAT3 , Transducción de Señal , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Apoptosis/fisiología , Transducción de Señal/fisiología , Recuperación de la Función/fisiología , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Ratas , Médula Espinal/metabolismo , Interleucina-6/metabolismo , Masculino , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: To observe the effects of 4 weeks of voluntary wheel running on depressive-like behavior in a rat chronic stress-induced depression model to explore the anti-depressive mechanism of exercise. METHODS: In this observational study, 36 Sprague-Dawley rats were randomly divided into control, stress model, and stress exercise groups (12 rats/group). The control group received no intervention, and the stress model and stress exercise group rats underwent chronic mild unpredictable stress and isolation. The stress exercise group rats also underwent 4 weeks of voluntary wheel running. Behavioral changes and hippocampal protein and mRNA expression levels were detected. RESULTS: Voluntary wheel running significantly increased horizontal and vertical movements, sucrose intake, and the sucrose preference percentage and reduced immobility time in the forced swimming test in depression model rats. The hippocampal tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, and quinolinic acid levels were significantly decreased, while the IL-4, IL-10, and kynurenic acid levels were significantly increased. Kynurenine-3-monooxygenase and 3-hydroxyanthranilate-3, 4-dioxygenase mRNA levels were downregulated, and kynurenine aminotransferase mRNA was upregulated. CONCLUSION: Voluntary wheel running improved depressive-like behavior in depression model rats. The mechanism may be related to a kynurenine pathway metabolite level imbalance, which has neurotoxic and neuroprotective effects, caused by long-term voluntary wheel running.
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Conducta Animal , Depresión , Hipocampo , Quinurenina , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Estrés Psicológico , Animales , Depresión/metabolismo , Depresión/etiología , Condicionamiento Físico Animal/métodos , Quinurenina/metabolismo , Estrés Psicológico/metabolismo , Estrés Psicológico/complicaciones , Masculino , Ratas , Hipocampo/metabolismo , Modelos Animales de Enfermedad , Transducción de SeñalRESUMEN
This study aimed to investigate how intermittent hyperoxic exposure (three cycles of 21% O2 [10 min] and 30% O2 [15 min]) affects exercise performance in mice. Three hours after the acute exposure, there was an observed increase in mRNA levels of phosphofructokinase (Bayes factor [BF] ≥ 10), mitochondrial transcription factor-A (BF ≥10), PPAR-α (BF ≥3), and PPAR-γ (BF ≥3) in the red gastrocnemius muscle (Gr). Four weeks of exercise training under intermittent (INT), but not continuous (HYP), hyperoxia significantly (BF ≥30) increased maximal exercise capacity compared to normoxic exercise-trained (ET) group. INT group exhibited significantly higher activity levels of 3-hydroxyacyl-CoA-dehydrogenase (HAD) in Gr (BF = 7.9) compared to ET group. Pyruvate dehydrogenase complex activity levels were significantly higher in INT group compared to ET group in white gastrocnemius, diaphragm, and left ventricle (BF ≥3). NT-PGC1α protein levels in Gr (BF = 7.7) and HAD activity levels in Gr (BF = 6.9) and soleus muscles (BF = 3.3) showed a significant positive correlation with maximal work values. These findings suggest that exercise training under intermittent hyperoxia is a beneficial strategy for enhancing endurance performance by improving fatty acid and pyruvic acid utilization.
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Músculo Esquelético , Condicionamiento Físico Animal , Resistencia Física , Animales , Masculino , Músculo Esquelético/metabolismo , Ratones , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Resistencia Física/fisiología , Ratones Endogámicos C57BL , Hiperoxia/metabolismo , Hiperoxia/fisiopatología , PPAR alfa/metabolismo , PPAR alfa/genética , PPAR gamma/metabolismo , PPAR gamma/genética , Fosfofructoquinasas/metabolismo , Fosfofructoquinasas/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN , Proteínas MitocondrialesRESUMEN
Alleviation of motor impairment by aerobic exercise (AE) in Parkinson's disease (PD) patients points to activation of neurobiological mechanisms that may be targetable by therapeutic approaches. However, evidence for AE-related recovery of striatal dopamine (DA) signaling or tyrosine hydroxylase (TH) loss has been inconsistent in rodent studies. This ambiguity may be related to the timing of AE intervention in relation to the status of nigrostriatal neuron loss. Here, we replicated human PD at diagnosis by establishing motor impairment with >80% striatal DA and TH loss prior to initiating AE, and assessed its potential to alleviate motor decline and restore DA and TH loss. We also evaluated if serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of human PD severity, changed in response to AE. 6-hydroxydopamine (6-OHDA) was infused unilaterally into rat medial forebrain bundle to induce progressive nigrostriatal neuron loss over 28 days. Moderate intensity AE (3× per week, 40 min/session), began 8-10 days post-lesion following establishment of impaired forelimb use. Striatal tissue DA, TH protein and mRNA, and serum levels of NfL/GFAP were determined 3-wks after AE began. Despite severe striatal DA depletion at AE initiation, forelimb use deficits and hypokinesia onset were alleviated by AE, without recovery of striatal DA or TH protein loss, but reduced NfL and GFAP serum levels. This proof-of-concept study shows AE alleviates motor impairment when initiated with >80% striatal DA loss without obligate recovery of striatal DA or TH protein. Moreover, the AE-related reduction of NfL and GFAP serum levels may serve as objective blood-based biomarkers of AE efficacy.
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Biomarcadores , Cuerpo Estriado , Dopamina , Oxidopamina , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa , Animales , Ratas , Tirosina 3-Monooxigenasa/metabolismo , Oxidopamina/toxicidad , Masculino , Cuerpo Estriado/metabolismo , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Biomarcadores/sangre , Dopamina/metabolismo , Dopamina/sangre , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína Ácida Fibrilar de la Glía/sangre , Índice de Severidad de la Enfermedad , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/metabolismo , Enfermedad de Parkinson/sangre , Terapia por Ejercicio/métodosRESUMEN
Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.
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Entrenamiento de Intervalos de Alta Intensidad , Histona Demetilasas con Dominio de Jumonji , Trastornos del Humor , Neuroglía , Condicionamiento Físico Animal , Animales , Ratones , Histona Demetilasas con Dominio de Jumonji/metabolismo , Neuroglía/metabolismo , Neuroglía/inmunología , Entrenamiento de Intervalos de Alta Intensidad/métodos , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Trastornos del Humor/metabolismo , Masculino , Corteza Prefrontal/metabolismo , Ratones Endogámicos C57BL , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Plasticidad Neuronal/fisiología , Encéfalo/metabolismo , Encéfalo/inmunología , Epigénesis Genética , Modelos Animales de Enfermedad , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Inflamación/metabolismo , Inflamación/inmunología , FemeninoRESUMEN
Moderate physical exercise has positive effects on memory. The present study aimed to investigate the impact of long-term exercise on spatial memory in developing mice, as well as its association with the cholinergic system, antioxidant activities, apoptosis factor, and BDNF/PI3K/Akt/CREB pathway in the brain. In this study, Y maze and Novel object recognition (NOR) tests were employed to assess the impact of long-term voluntary exercise on memory. The cholinergic system, antioxidant activities, and apoptosis factors in the brain were quantified using Elisa. Additionally, western blot analysis was conducted to determine the expression of relevant proteins in the BDNF/PI3K/Akt/CREB pathway. The findings demonstrated that prolonged voluntary wheel running exercise enhanced memory in developing mice, concomitant with increased catalase (CAT) activity and decreased malondialdehyde (MDA) levels in the brain. Moreover, it could also increase the hippocampal acetylcholine (ACh) content and suppress the expression of neuronal apoptosis protein. Additionally, exercise also upregulated the expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphoinositide 3 kinases (PI3K), Akt, cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB) in the hippocampus. These findings suggest that long-term voluntary wheel running exercise improves the spatial memory of developing mice by modulating the cholinergic system, antioxidant activities, apoptosis factors, and activating the BDNF/PI3K/Akt/CREB pathway.
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Antioxidantes , Factor Neurotrófico Derivado del Encéfalo , Cognición , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Fosfatidilinositol 3-Quinasas , Condicionamiento Físico Animal , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Ratones , Transducción de Señal/fisiología , Masculino , Antioxidantes/metabolismo , Cognición/fisiología , Hipocampo/metabolismo , Carrera/fisiología , Carrera/psicología , Acetilcolina/metabolismo , Aprendizaje por Laberinto/fisiología , Memoria Espacial/fisiologíaRESUMEN
Voluntary or forced exercise training in mice is used to assess functional capacity as well as potential disease-modifying effects of exercise over a range of cardiovascular disease phenotypes. Compared to voluntary wheel running, forced exercise training enables precise control of exercise workload and volume, and results in superior changes in cardiovascular performance. However, the use of a shock grid with treadmill-based training is associated with stress and risk of injury, and declining compliance with longer periods of training time for many mouse strains. With these limitations in mind, we designed a novel, high-intensity interval training modality (HIIT) for mice that is carried out on a rotarod. Abbreviated as RotaHIIT, this protocol establishes interval workload intensities that are not time or resource intensive, maintains excellent training compliance over time, and results in improved exercise capacity independent of sex when measured by treadmill graded exercise testing (GXT) and rotarod specific acceleration and endurance testing. This protocol may therefore be useful and easily implemented for a broad range of research investigations. As RotaHIIT training was not associated cardiac structural or functional changes, or changes in oxidative capacity in cardiac or skeletal muscle tissue, further studies will be needed to define the physiological adaptations and molecular transducers that are driving the training effect of this exercise modality.
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Ratones Endogámicos C57BL , Condicionamiento Físico Animal , Animales , Ratones , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Masculino , Femenino , Entrenamiento de Intervalos de Alta Intensidad/métodos , Tolerancia al Ejercicio/fisiología , Músculo Esquelético/fisiología , Prueba de Desempeño de Rotación con Aceleración Constante/métodosRESUMEN
BACKGROUND: In the present study, we investigated the effect of high-intensity interval training (HIIT) on cognitive behaviors in female rats with a high-fat diet + streptozotocin (STZ)-induced type 2 diabetes. METHODS: Twenty-four female rats were divided into four groups randomly (n = 6): control (C), control + exercise (Co + EX), diabetes mellitus (type 2) (T2D), and diabetes mellitus + exercise (T2D + EX). Diabetes was induced by a two-month high-fat diet and a single dose of STZ (35 mg/kg) in the T2D and T2D + EX groups. The Co + EX and T2D + EX groups performed HIIT for eight weeks (five sessions per week, running on a treadmill at 80-100% of VMax, 4-10 intervals). Elevated plus maze (EPM) and open field test (OFT) were used for assessing anxiety-like behaviors, and passive avoidance test (PAT) and Morris water maze (MWM) were applied for evaluating learning and memory. The hippocampal levels of beta-amyloid (Aß) and Tau were also assessed using Western blot. RESULTS: An increase in fasting blood glucose (FBG), hippocampal level of Tau, and a decrease in the percentage of open arm time (%OAT) as an index of anxiety-like behavior were seen in the female diabetic rats which could be reversed by HIIT. In addition, T2D led to a significant decrease in rearing and grooming in the OFT. No significant difference among groups was seen for the latency time in the PAT and learning and memory in the MWM. CONCLUSIONS: HIIT could improve anxiety-like behavior at least in part through changes in hippocampal levels of Tau.
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Péptidos beta-Amiloides , Ansiedad , Diabetes Mellitus Experimental , Hipocampo , Condicionamiento Físico Animal , Proteínas tau , Animales , Femenino , Hipocampo/metabolismo , Proteínas tau/metabolismo , Ratas , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/psicología , Ansiedad/terapia , Ansiedad/psicología , Ansiedad/metabolismo , Péptidos beta-Amiloides/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/psicología , Diabetes Mellitus Experimental/terapia , Entrenamiento de Intervalos de Alta Intensidad/métodos , Aprendizaje por Laberinto/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/terapia , Conducta Animal/fisiología , Dieta Alta en Grasa/efectos adversos , Ratas Sprague-DawleyRESUMEN
This study aimed to determine whether heat acclimation could induce adaptations in exercise performance, thermoregulation, and the expression of proteins associated with heat stress in the skeletal muscles of Thoroughbreds. Thirteen trained Thoroughbreds performed 3 weeks of training protocols, consisting of cantering at 90% maximal oxygen consumption (VO2max) for 2 min 2 days/week and cantering at 7 m/s for 3 min 1 day/week, followed by a 20-min walk in either a control group (CON; Wet Bulb Globe Temperature [WBGT] 12-13°C; n = 6) or a heat acclimation group (HA; WBGT 29-30°C; n = 7). Before and after heat acclimation, standardized exercise tests (SET) were conducted, cantering at 7 m/s for 90 s and at 115% VO2max until fatigue in hot conditions. Increases in run time (p = 0.0301), peak cardiac output (p = 0.0248), and peak stroke volume (p = 0.0113) were greater in HA than in CON. Pulmonary artery temperature at 7 m/s was lower in HA than in CON (p = 0.0332). The expression of heat shock protein 70 (p = 0.0201) and 90 (p = 0.0167) increased in HA, but not in CON. These results suggest that heat acclimation elicits improvements in exercise performance and thermoregulation under hot conditions, with a protective adaptation to heat stress in equine skeletal muscles.
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Aclimatación , Proteínas HSP70 de Choque Térmico , Músculo Esquelético , Condicionamiento Físico Animal , Animales , Caballos/fisiología , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Proteínas HSP70 de Choque Térmico/metabolismo , Aclimatación/fisiología , Masculino , Calor , Regulación de la Temperatura Corporal/fisiología , Consumo de Oxígeno/fisiología , Respuesta al Choque Térmico/fisiologíaRESUMEN
AIMS: Parkinson's disease (PD) is characterized by loss of dopamine neurons in the brain, which leads to motor dysfunction; excessive inflammation induces neuronal death. This study aimed to determine the most effective exercise modality to improve motor dysfunction in PD by comparing three different exercise regimens (low-intensity treadmill, high-intensity treadmill, and swimming). MATERIALS AND METHODS: The rat model for PD was established through stereotaxic surgery, inducing unilateral 6-OHDA (6-hydroxydopamine) lesions. The low-intensity treadmill regimen exerted better protective effects on neurological and motor functions in a rat model of unilateral 6-OHDA-induced PD compared to high-intensity treadmill and swimming. The most suitable exercise regimen and the optimal duration of daily exercise (15 or 30 min) on motor activity and oxidative stress parameters were evaluated. KEY FINDINGS: Comparison of 15 and 30 min low-intensity treadmill regimens (10 m/min) revealed 30 min daily exercise was the optimal duration and had more favorable impacts on neurological and motor function. Furthermore, we assessed the neuroprotective effects of exercising for 15 and 30 min per day for either four or ten weeks; 30 min of daily exercise for ten weeks improved mitochondrial function, the antioxidant defense system, neurotrophic factors, and muscle mass, and thereby provided protection against dopaminergic neuron loss, and motor dysfunction in rats with 6-OHDA-induced PD. SIGNIFICANCE: 30 min of daily low-intensity treadmill exercise over 10 weeks resulted in heightened mitochondrial function in both muscle and brain tissues, therefore, yielded a neuroprotective effect against the loss of dopaminergic neurons and motor dysfunction in PD rats.
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Modelos Animales de Enfermedad , Mitocondrias , Estrés Oxidativo , Oxidopamina , Enfermedad de Parkinson , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Animales , Ratas , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Masculino , Mitocondrias/metabolismo , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Terapia por Ejercicio/métodos , Actividad Motora/fisiologíaRESUMEN
Exercise increases the expression of brain-derived neurotrophic factor (BDNF) in the brain and contributes to cognitive and sensorimotor functions. This study aimed to elucidate how repeated exercise modifies BDNF expression elicited by a single bout of exercise in the brain using in vivo bioluminescence imaging (BLI). Bdnf-luciferase (Luc) mice with the firefly luciferase gene inserted at the translation start point of the Bdnf gene were used for BLI to monitor changes in BDNF expression in the brain. The treadmill exercise at a speed of 10 m/s for 60 min was repeated 5 days a week for 4 weeks. BLI in individual subjects was repeated four times: before the exercise intervention, on the first exercise day, and 14 and 28 days after the start of the intervention. Each BLI was performed after a single bout of exercise and monitored for 8 h after exercise. Repetitive BLI showed that the exercise regimen enhanced BDNF expression in the brain, specifically at 4-8 h after a single bout of exercise. Repeated exercise for 2 weeks accelerated the start of enhancement after a single bout of exercise, but not after 4 weeks of repeated exercise. This study showed that repeated exercise modulated the time window of exercise-enhanced BDNF expression, suggesting that repeated exercise could change the sensitivity of gene expression to a single bout of exercise. These findings can be attributed to the advantages of in vivo BLI, which allowed us to precisely measure the time course of BDNF expression after repeated exercise in individual subjects.
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Factor Neurotrófico Derivado del Encéfalo , Encéfalo , Mediciones Luminiscentes , Condicionamiento Físico Animal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Animales , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Encéfalo/metabolismo , Mediciones Luminiscentes/métodos , Masculino , Ratones , Factores de Tiempo , Ratones Endogámicos C57BLRESUMEN
Mitochondria play a crucial role in maintaining cellular energy supply and serve as a source of energy for repairing nerve damage following a stroke. Given that exercise has the potential to enhance energy metabolism, investigating the impact of exercise on mitochondrial function provides a plausible mechanism for stroke treatment. In our study, we established the middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats and implemented early exercise intervention. Neurological severity scores, beam-walking test score, and weight were used to evaluate neurological function. The volume of cerebral infarction was measured by MRI. Nerve cell apoptosis was detected by TUNEL staining. Mitochondrial morphology and structure were detected by mitochondrial electron microscopy. Mitochondrial function was assessed using membrane potential and ATP measurements. Western blotting was used to detect the protein expression of AMPK/PGC-1α/GLUT4. Through the above experiments, we found that early exercise improved neurological function in rats after MCAO, reduced cerebral infarction volume and neuronal apoptosis, promoted the recovery of mitochondrial morphology and function. We further examined the protein expression of AMPK/PGC-1α/GLUT4 signaling pathway and confirmed that early exercise was able to increase its expression. Therefore, we suggest that early exercise initiated the AMPK/PGC-1α/GLUT4 signaling pathway, restoring mitochondrial function and augmenting energy supply. This, in turn, effectively improved both nerve and body function in rats following ischemic stroke.
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Proteínas Quinasas Activadas por AMP , Mitocondrias , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Transducción de Señal , Animales , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Transducción de Señal/fisiología , Masculino , Proteínas Quinasas Activadas por AMP/metabolismo , Mitocondrias/metabolismo , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/terapia , Isquemia Encefálica/metabolismo , Ratas , Modelos Animales de Enfermedad , Apoptosis/fisiologíaRESUMEN
The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1ß), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1ß, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1ß, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse.
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Cardiotoxicidad , Suplementos Dietéticos , Modelos Animales de Enfermedad , Cardiopatías , Interleucina-18 , Metanfetamina , Condicionamiento Físico Animal , Piroptosis , Ratas Wistar , Animales , Metanfetamina/toxicidad , Metanfetamina/administración & dosificación , Masculino , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Piroptosis/efectos de los fármacos , Interleucina-18/metabolismo , Interleucina-18/genética , Cardiopatías/inducido químicamente , Cardiopatías/prevención & control , Cardiopatías/patología , Cardiopatías/fisiopatología , Cardiopatías/metabolismo , Síndrome de Abstinencia a Sustancias/fisiopatología , Síndrome de Abstinencia a Sustancias/metabolismo , Síndrome de Abstinencia a Sustancias/prevención & control , Caspasa 1/metabolismo , Caspasa 1/genética , Estimulantes del Sistema Nervioso Central/toxicidad , Estimulantes del Sistema Nervioso Central/administración & dosificación , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Miocardio/metabolismo , Miocardio/patología , Ratas , Trastornos Relacionados con Anfetaminas/fisiopatología , Trastornos Relacionados con Anfetaminas/metabolismo , Trastornos Relacionados con Anfetaminas/terapia , Factores de TiempoRESUMEN
OBJECTIVE: To identify subclinical left ventricle dysfunction (LVD) in obese rats by speckle-tracking echocardiography, and to evaluate the effects of 12-week Moderate-Intensity Continuous Training (MICT) or High-Intensity Interval Training (HIIT) on LV geometry, histology and function in obese rats. METHODS: Eighteen male standard or obese Sprague-Dawley rats were randomly divided into the Control group, the MICT group, and the HIIT group. Exercise interventions were conducted for 12 weeks, with equal total load and increased intensity gradient. Using dual-energy X-ray, two-dimensional speckle-tracking echocardiography, pulse Doppler, and HE staining to evalucate body shape, LV morphology, structure, and myocardial mechanics function. RESULTS: (1) Both MICT and HIIT have good weight loss shaping effect. (2) The LV of obese rats underwent pathological remodeling, with decreased longitudinal contractility and synchrony, and increased circumferential contractility and synchrony. (3) Exercise can inhibit LV pathological remodeling, improve myocardial mechanical function. HIIT is superior to MICT. (4) The global longitudinal strain of obese rats in the HIIT group showed a significant correlation with Fat% and Lean%. CONCLUSION: Obesity can induce LV pathological remodeling and subclinical dysfunction. Compared with MICT, 12-week HIIT can effectively inhibit the pathological remodeling of LV and promote the benign development of myocardial mechanical function in obese rats.
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Ecocardiografía , Obesidad , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Disfunción Ventricular Izquierda , Animales , Obesidad/fisiopatología , Obesidad/terapia , Obesidad/complicaciones , Masculino , Ratas , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Condicionamiento Físico Animal/métodos , Ecocardiografía/métodos , Entrenamiento de Intervalos de Alta Intensidad/métodos , Remodelación Ventricular , Modelos Animales de EnfermedadRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and moderate exercise holds promise in ameliorating the ongoing neurodegeneration and cognitive decline. Here, we investigated whether exercise-enriched blood plasm could yield a beneficial therapeutic effect on AD pathologies and cognitive decline in transgenic AD (P301S) mice. In this investigation, a cohort of 2-month-old C57BL/6 mice were granted continuous access to either a running wheel or a fixed wheel for 6 weeks. After that, their plasmas were extracted and subsequently injected intravenously into 4.5-month-old P301S mice biweekly over a 6-week period. A comprehensive methodology was then employed, integrating behavioral tests, pathology assessments, and biochemical analyses to unveil the potential anti-dementia implications of exercise-enriched blood plasma in P301S mice. Upon systemic administration, the findings revealed a noteworthy attenuation of hippocampus-dependent behavioral impairments in P301S mice. Conversely, blood plasma from sedentary counterparts exhibited no discernible impact. These effects were intricately associated with the mitigation of neuroinflammation, the augmentation of hippocampal adult neurogenesis, and a reduction of synaptic impairments following the administration of exercise-enriched blood plasma. These findings advance the proposition that administering exercise-enriched blood plasma may serve as an effective prophylactic measure against AD, opening avenues for further exploration and potential therapeutic interventions.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Modelos Animales de Enfermedad , Hipocampo , Ratones Endogámicos C57BL , Ratones Transgénicos , Condicionamiento Físico Animal , Animales , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/sangre , Hipocampo/metabolismo , Hipocampo/patología , Condicionamiento Físico Animal/métodos , Disfunción Cognitiva/terapia , Disfunción Cognitiva/sangre , Ratones , Plasma/metabolismo , Masculino , NeurogénesisRESUMEN
Hypertensive postmenopausal women are more likely to develop adverse cardiac remodeling and respond less effectively to drug treatment than men. High-intensity interval exercise (HIIE) is a nonpharmacological strategy for the treatment of hypertension; however, the effectiveness in women remains uncertain. This study was designed to evaluate 1) the effects of HIIE training upon morphological and functional markers of cardiovascular health in female SHR and 2) to determine whether the hormonal shift induced by ovariectomy could influence cardiovascular responses to HIIE. Thirty-six SHR were randomly assigned to four groups: ovariectomized sedentary, ovariectomized trained, sham-operated sedentary, and sham-operated trained. The trained rats performed HIIE 5 days/wk for 8 wk. Blood pressure and echocardiographic measurements were performed before and after training in animals. Cardiac response to ß-adrenergic stimulation and the expression of calcium regulatory proteins and estrogen receptors in heart samples were assessed. Endothelium-dependent vasorelaxation in response to acetylcholine was evaluated in aortic rings as well as the expression of nitric oxide synthase isoforms (eNOS and P-eNOS) by Western blotting. In both groups of trained SHR, HIIE induced eccentric cardiac remodeling with greater inotropic and chronotropic effects, as well as an increase in SERCA and ß1AR expression. However, although the trained rats showed improved endothelial function and expression of eNOS and P-eNOS in the aorta, there was no demonstrated effect on blood pressure. In addition, the responses to HIIE training were not affected by ovariectomy. This work highlights the importance of assessing the cardiovascular efficacy and safety of different exercise modalities in women.NEW & NOTEWORTHY This study reports the effects of high-intensity interval exercise (HIIE) training on cardiac and endothelial function in female hypertensive rats. Despite a lack of effect on blood pressure (BP), HIIE training induces eccentric cardiac remodeling with greater functionals effects. Furthermore, training has beneficial effects on endothelial function. However, ovarian hormones do not seem to modulate cardiac and aortic adaptations to this training modality. All this underlines the need to consider training modalities on the cardiovascular system in women.
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Presión Sanguínea , Entrenamiento de Intervalos de Alta Intensidad , Hipertensión , Ovariectomía , Condicionamiento Físico Animal , Ratas Endogámicas SHR , Animales , Femenino , Entrenamiento de Intervalos de Alta Intensidad/métodos , Ratas , Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Hipertensión/metabolismo , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Remodelación Ventricular/fisiologíaRESUMEN
The developmental origins of health and disease concept highlights the impact of early environments on chronic non-communicable diseases like diabetes, cardiovascular disease, and cancer. Studies using animal models have investigated how maternal factors such as undernutrition, overnutrition, obesity, and exposure to chemicals or hypoxia affect fetal development and offspring health, leading to issues like low birth weight, high blood pressure, dyslipidemia, and insulin resistance. Given the increasing prevalence of overweight and obesity among reproductive-age women, effective interventions are critical. Maternal exercise during pregnancy has emerged as a key intervention, benefiting both mother and offspring and reducing the risk of disease. This study compares the differences of three exercise models on pregnant rats: voluntary wheel running, motorized treadmills, and swimming. Swimming is the most beneficial option due to its safe and controlled intensity levels. This protocol details the rat breeding methods, swimming training during pregnancy, and post-breeding nursing protocols. This model, suitable for various rat and mouse species, is useful for studying the benefits of maternal exercise on offspring health and intergenerational wellness.