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OBJECTIVE: To describe the effects of strength exercise practice during pregnancy on the offspring's development parameters: growth and motor performance, hippocampal neuroplasticity, and stress levels. METHODS: Pregnant Wistar rats were divided into two groups: sedentary and exercised rats. Exercised pregnant rats were subjected to a strength training protocol (vertical ladder climbing) throughout the gestational period. Male offspring's body weight, length, and head size were evaluated during the neonatal period (postnatal days [P]2-P21), as well as motor milestones during P0-P8. At P8, a set of male pups were subjected to global hippocampal DNA methylation, hippocampal cell proliferation, and plasma corticosterone concentration. RESULTS: Offspring from trained mothers presented a transient change in body morphometric evaluations, no differences in milestone assessments, enhancement of cell proliferation in the dentate gyrus of the hippocampus, and decreased global hippocampal DNA methylation compared with the offspring from sedentary mothers. Furthermore, strength training during pregnancy did not change the corticosterone concentration of exercised mothers and their offspring. CONCLUSIONS: These data indicate that strength training can protect offspring's development and could impact positively on parameters linked to cognitive function. This study provides a greater understanding of the effects of strength exercise practiced during pregnancy on the offspring's health.
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Entrenamiento de Fuerza , Animales , Animales Recién Nacidos , Corticosterona , Femenino , Hipocampo , Humanos , Masculino , Embarazo , Ratas , Ratas WistarRESUMEN
Maternal diabetes constitutes an unfavorable intrauterine environment for offspring development. Although it is known that diabetes can cause brain alterations and increased risk for neurologic disorders, the relationship between neuroimmune activation, brain changes, and neurodevelopment deficits in the offspring remains unclear. In order to elucidate the short- and long-term biological basis of the developmental outcomes caused by the severe uncontrolled maternal hyperglycemia, we studied apoptosis, neurogenesis, and neuroinflammation pathways in the hippocampus of neonates and young rats born to diabetic dams. Diabetes was induced on gestational day 5 by an injection of streptozotocin. Evaluations of milestones, body growth, and inhibitory avoidance were performed to monitor the offspring development and behavior. Hippocampal modifications were studied through cellular survival by BrdU in the dentate gyrus, expression of apoptosis-regulatory proteins (procaspase 3, caspase 3, and Bcl-2), BDNF, and neuroinflammatory modulation by interleukins, MHC-I, MHC-II, Iba-1, and GFAP proteins. Severe maternal diabetes caused microsomia and neurodevelopmental delay in pups and decrease of Bcl-2, procaspase 3, and caspase 3 in the hippocampus. Moreover, in a later stage of development, it was found an increase of TNF-α and a decrease of procaspase 3, caspase 3, MHC-I, IL-1ß, and BDNF in the hippocampus, as well as impairment in cellular survival in the dentate gyrus. This study showed significant short- and long-term commitments on the development, apoptosis, cell survival, and neuroinflammation in the offspring hippocampus induced by severe uncontrolled maternal hyperglycemia. The data reinforce the need for treatment of maternal hyperglycemic states during pregnancy and breast-feeding.
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Apoptosis , Hipocampo/crecimiento & desarrollo , Hipocampo/patología , Hiperglucemia/complicaciones , Inflamación/patología , Efectos Tardíos de la Exposición Prenatal/patología , Glándulas Suprarrenales/patología , Animales , Animales Recién Nacidos , Reacción de Prevención , Peso Corporal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Supervivencia Celular , Citocinas/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Hígado/patología , Tamaño de los Órganos , Embarazo , Ratas Wistar , Estreptozocina , Timo/patologíaRESUMEN
Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic-pituitary-adrenal axis and microglial activation in diabetic animals.
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Diabetes Mellitus Experimental/psicología , Ambiente , Hipocampo/fisiopatología , Trastornos de la Memoria/prevención & control , Microglía/inmunología , Animales , Glucemia/análisis , Encéfalo/inmunología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Proteínas de Unión al Calcio/análisis , Corticosterona/sangre , Replicación del ADN , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inmunología , Conducta Exploratoria , Hipocampo/inmunología , Hipocampo/metabolismo , Vivienda para Animales , Masculino , Trastornos de la Memoria/sangre , Trastornos de la Memoria/etiología , Proteínas de Microfilamentos/análisis , Actividad Motora , Neurogénesis , Distribución Aleatoria , Ratas , Ratas Wistar , Reconocimiento en Psicología , Método Simple Ciego , Aprendizaje Espacial , Estreptozocina , Sinaptofisina/análisisRESUMEN
Transplantation with olfactory ensheathing cells (OECs) has been adopted after several models of spinal cord injury (SCI) with the purpose of creating a favorable environment for the re-growth of injured axons. However, a consensus on the efficacy of this cellular transplantation has yet to be reached. In order to explore alternative parameters that could demonstrate the possible restorative properties of such grafts, the present study investigated the effects of olfactory lamina propria (OLP) transplantation on hyperreflexia and myelinated fiber regeneration in adult rats with complete spinal cord transection. The efficacy of OLP (graft containing OECs) and respiratory lamina propria (RLP, graft without OECs) was tested at different post-injury times (acutely, 2- and 4-week delayed), to establish the optimum period for transplantation. In the therapeutic windows used, OLP and RLP grafts produced no considerable improvements in withdrawal reflex responses or on the low-frequency dependent depression of H-reflex. Both lamina propria grafts produced comparable results for the myelinated fiber density and for the estimated total number of myelinated fibers at the lesion site, indicating that the delayed transplantation approach does not seem to limit the regenerative effects. However, animals transplanted with OLP 2 or 4 weeks after injury exhibit smaller myelin sheath thickness and myelinated fiber area and diameter at the lesion site compared to their respective RLP groups. Despite the ongoing clinical use of OECs, it is important to emphasize the need for more experimental studies to clarify the exact nature of the repair capacity of these grafts in the treatment of SCI.
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Fibras Nerviosas Mielínicas/fisiología , Regeneración Nerviosa/fisiología , Mucosa Olfatoria/trasplante , Reflejo Anormal/fisiología , Traumatismos de la Médula Espinal/cirugía , Animales , Reflejo H/fisiología , Masculino , Membrana Mucosa/fisiología , Membrana Mucosa/trasplante , Mucosa Olfatoria/fisiología , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatología , Trasplante de Tejidos/métodosRESUMEN
Promising evidence points to gestational physical exercise as the key to preventing various disorders that affect the offspring neurodevelopment, but there are no studies showing the impact of resistance exercise on offspring health. Thus, the aim of this study was to investigate whether resistance exercise during pregnancy is able to prevent or to alleviate the possible deleterious effects on offspring, caused by early life-stress (ELS). Pregnant rats performed resistance exercise throughout the gestational period:they climbed a sloping ladder with a weight attached to their tail, 3 times a week. Male and female pups, on the day of birth (P0), were divided into 4 experimental groups: 1) rats of sedentary mothers (SED group); 2) rats of exercised mothers (EXE group); 3) rats of sedentary mothers and submitted to maternal separation (ELS group) and 4) rats of exercised mothers and submitted to MS (EXE + ELS group). From P1 to P10, pups from groups 3 and 4 were separated from their mothers for 3 h/day. Maternal behavior was assessed. From P30, behavioral tests were performed and on P38 the animals were euthanized and prefrontal cortex samples were collected. Oxidative stress and tissue damage analysis by Nissl staining were performed. Our results demonstrate that male rats are more susceptible to ELS than females, showing impulsive and hyperactive behavior similar to that seen in children with ADHD. This behavior was attenuated by the gestational resistance exercise. Our results demonstrate, for the first time, that resistance exercise performed during pregnancy seems to be safe for the pregnancy and offspring's neurodevelopment and are effective in preventing ELS-induced damage only in male rats. Interestingly, resistance exercise during pregnancy improved maternal care and it is reasonable to propose that this finding may be related to the protective role on the animals neurodevelopment, observed in our study.
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Experiencias Adversas de la Infancia , Entrenamiento de Fuerza , Embarazo , Humanos , Ratas , Animales , Femenino , Masculino , Ratas Wistar , Privación Materna , MadresRESUMEN
Astrocytic changes have been demonstrated in several neurodegenerative diseases, showing that these cells play an important role in functional recovery/maintenance against brain damage. Physical exercise is known to contribute to this process; however, the cellular mechanisms involved are not fully understood. This study investigated the effects of physical exercise on motor deficits and the expression of glial fibrillary acidic protein (GFAP) in a model of Parkinson's disease (PD). Rats were divided into four groups: sham sedentary (SS) and sham trained (ST); lesioned sedentary (LS) and lesioned trained (LT). 6-OHDA was infused unilaterally into the medial forebrain bundle. Behavioral tasks were applied to evaluate motor abilities. Tyrosine hydroxylase (TH-in substantia nigra) and GFAP (in striatum) immunoreactivities (ir) were semi-quantified using optical density. The animals submitted to treadmill training completed fewer pharmacological-induced rotations when compared with sedentary animals and they also showed ameliorated motor impairments. Interestingly, although no change in TH-ir, the exercise led to restored striatal GFAP expression in the LT group while there was no effect in the ST group. This study is the first study to show data indicating the recovery of GFAP expression post-exercise in this model and further research is necessary to determine the precise action mechanisms of exercise on astrocytes in the PD.
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Cuerpo Estriado/metabolismo , Proteína Ácida Fibrilar de la Glía/biosíntesis , Actividad Motora/fisiología , Condicionamiento Físico Animal , Adrenérgicos/toxicidad , Animales , Cuerpo Estriado/fisiopatología , Inmunohistoquímica , Masculino , Oxidopamina/toxicidad , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/fisiopatología , Ratas , Ratas WistarRESUMEN
Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.
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Plasticidad Neuronal , Traumatismos de la Médula Espinal/fisiopatología , Sinapsis/fisiología , Caminata , Animales , Western Blotting , Masculino , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Numerous therapeutic interventions have been tested to enhance functional recovery after peripheral nerve injuries. METHODS: After sciatic nerve crush in rats we tested balance and coordination and motor control training in sensorimotor tests and analyzed nerve and muscle histology. RESULTS: The balance and coordination training group and the sham group had better results than the sedentary and motor control groups in sensorimotor tests. The sham and balance and coordination groups had a significantly larger muscle area than the other groups, and the balance and coordination group showed significantly better values than the sedentary and motor control groups for average myelin sheath thickness and g-ratio of the distal portion of the nerve. CONCLUSIONS: The findings indicate that balance and coordination training improves sciatic nerve regeneration, suggesting that it is possible to revert and/or prevent soleus muscle atrophy and improve performance on sensorimotor tests.
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Terapia por Ejercicio , Equilibrio Postural/fisiología , Desempeño Psicomotor/fisiología , Recuperación de la Función/fisiología , Neuropatía Ciática/fisiopatología , Neuropatía Ciática/rehabilitación , Animales , Terapia por Ejercicio/métodos , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Studies indicate that gestational exercise practice positively impacts the offspring's cognition. Nevertheless, the influence of maternal resistance exercise, different periods of exercise practice, and the inter- and transgenerational effects involved in these responses are not known. This study sought to report the influence of the maternal practice of resistance exercise on offspring's cognitive function, exploring behavior, and neuroplastic and epigenetic marks in the hippocampus. Female Wistar rats were divided into four groups: sedentary (SS), exercised during pregnancy (SE), exercised before pregnancy (ES), and exercised before and during pregnancy (EE). Exercised rats were submitted to a resistance exercise protocol (vertical ladder climbing). Between postnatal days (P)81 and P85, male offspring were submitted to the Morris water maze test. At P85, the following analyses were performed in offspring's hippocampus: expression of IGF-1 and BrdU+ cells, global DNA methylation, H3/H4 acetylation, and HDAC2 amount. Only the offspring of SE mothers presented subtly better performance on learning and memory tasks, associated with lower HDAC2 amount. Offspring from ES mothers presented an overexpression of hippocampal neuroplastic marks (BrdU+ and IGF-1), as well as a decrease of DNA methylation and an increase in H4 acetylation. Offspring from EE mothers (continuously exercised) did not present modifications in plasticity or epigenetic parameters. This is the first study to observe the influence of maternal resistance exercise on offspring's brains. The findings provide evidence that offspring's hippocampus plasticity is influenced by exercise performed in isolated periods (pre- or gestationally) more than that performed continually.
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Entrenamiento de Fuerza , Adulto , Animales , Epigénesis Genética , Femenino , Hipocampo , Humanos , Masculino , Memoria , Embarazo , Ratas , Ratas WistarRESUMEN
The serotoninergic system modulates nociceptive and locomotor spinal cord circuits. Exercise improves motor function and changes dopaminergic, noradrenergic, and serotonergic central systems. However, the direct relationship between serotonin, peripheral nerve lesion and aerobic treadmill exercise has not been studied. Using immunohistochemistry and optic densitometry, this study showed that the sciatic nerve transection increased the serotoninergic immunoreactivity in neuronal cytoplasm of the magnus raphe nuclei of trained and sedentary rats. In the dorsal raphe nucleus the increase only occurred in sedentary-sham-operated rats. In the spinal cord of trained, transected rats, the ventral horn showed significant changes, while the change in dorsal horn was insignificant. Von Frey's test indicated analgesia in all exercise-trained rats. The sciatic nerve functional index indicated recovery in the trained group. Thus, both the aerobic treadmill exercise training and the nervous lesion appear to contribute to changes in serotonin immunoreactivity.
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Condicionamiento Físico Animal/fisiología , Núcleos del Rafe/metabolismo , Nervio Ciático/fisiología , Serotonina/metabolismo , Médula Espinal/metabolismo , Aerobiosis , Animales , Citrato (si)-Sintasa/metabolismo , Densitometría , Miembro Posterior/fisiología , Inmunohistoquímica , Masculino , Músculo Esquelético/metabolismo , Dimensión del Dolor , Resistencia Física , Estimulación Física , Ratas , Ratas WistarRESUMEN
The intracerebroventricular infusion of streptozotocin (icv-STZ) has been largely used in research to mimic the main characteristics of Alzheimer's disease (AD), including cognitive decline, impairment of cholinergic transmission, oxidative stress and astrogliosis. Moderate physical exercise has a number of beneficial effects on the central nervous system, as demonstrated both in animals and in human studies. This study aimed to evaluate the effect of 5-week treadmill training, in the icv-SZT model of sporadic AD, on cognitive function, oxidative stress (particularly mediated by NO) and on the astrocyte marker proteins, glial fibrillary acidic protein (GFAP) and S100B. Results confirm the spatial cognitive deficit and oxidative stress in this model, as well as astroglial alterations, particularly a decrease in CSF S100B. Physical exercise prevented these alterations, as well as increasing the hippocampal content of glutathione and GFAP per se in the CA1 region. These findings reinforce the potential neuroprotective role of moderate physical exercise. Astroglial changes observed in this dementia model contribute to understanding AD and other diseases that are accompanied by cognitive deficit.
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Trastornos del Conocimiento/rehabilitación , Hipocampo/fisiología , Actividad Motora/fisiología , Estrés Oxidativo/fisiología , Enfermedad de Alzheimer/rehabilitación , Animales , Trastornos del Conocimiento/inducido químicamente , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutatión/metabolismo , Hipocampo/efectos de los fármacos , Inmunohistoquímica , Inyecciones Intraventriculares , Masculino , Aprendizaje por Laberinto/fisiología , Neurotoxinas/administración & dosificación , Neurotoxinas/toxicidad , Ratas , Ratas Wistar , Estreptozocina/administración & dosificación , Estreptozocina/toxicidadRESUMEN
Intrauterine exposure to exercise is beneficial to cognition of the offspring. Although it is advisable to start practicing physical exercise during pregnancy, it is probable that practitioners or sedentary women keep their previous habits during gestation. This study was designed to evaluate the effects of maternal aerobic exercise initiated before and maintained during gestation, or performed in these isolated periods, on cognition and plasticity in the hippocampus of offspring. Groups of male pups were categorized by the exposure of their mothers to: treadmill off (sedentary, SS), pregestational exercise (ES), gestational exercise (SE) or combined protocols (EE). Between postnatal day 20 (P20) and P23 the offspring received one daily 5-bromo-2'-deoxiuridine (BrdU) injection and, from P47 to P51, were evaluated by the Morris water maze task. At P53, hippocampal global DNA methylation, survival of progenitor cells (BrdU), Brain-derived Neurotrophic Factor (BDNF) and reelin levels were measured. The offspring from ES, SE and EE mothers demonstrated improved spatial learning compared to SS, but hippocampal DNA methylation was significantly modified only in the offspring from ES mothers. The offspring from ES and SE mothers presented higher number of BrdU+ and reelin+ hippocampal cells than EE and SS. No differences were observed in the BDNF levels among the groups. The maternal pregestational and gestational isolated exercise protocols showed similar effects for offspring plasticity and spatial cognitive ability, while the combined protocol simply improved their spatial learning. Interestingly, only pregestational exercise was able to induce plasticity in the offspring hippocampus associated with modulation of global DNA methylation.
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Conducta Animal/fisiología , Metilación de ADN/fisiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Aprendizaje Espacial/fisiología , Animales , Cognición/fisiología , Femenino , Aprendizaje por Laberinto/fisiología , Condicionamiento Físico Animal/métodos , Embarazo , Ratas Wistar , Proteína ReelinaRESUMEN
It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2'-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2'-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear.
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The aim of the present study was to investigate whether treadmill locomotor training could have beneficial effects on deficits consequent to perinatal anoxia, sensorimotor restriction or a combination of both. Fifty-six newborn male Wistar rats were divided into four groups: control, anoxic, sensorimotor-restricted and anoxic-sensorimotor-restricted. Rats were exposed to anoxia in the first two postnatal days (P0 and P1) and/or hind-limb sensorimotor restriction from P2 to P28 for 16 h/day. Control and experimental rats underwent treadmill training for three weeks (from P31 to P52). Body weight and walking patterns (stride length and foot angle) were measured weekly during treadmill locomotor training. Soleus muscle cross-sectional mean area and fiber density were measured using planar morphometry. Anoxia per se did not cause gait or muscle deficits. Body weight, stride length and soleus fiber cross-sectional mean area, however, were increased in trained anoxic rats. Sensorimotor-restricted animals, either with or without perinatal anoxia, showed deficits in body weight gain, decreased stride length, wider foot angle and soleus fiber atrophy. In the sensorimotor-restricted group, treadmill training improved body weight gain and stride length, and decreased the percentage of the atrophic fibers. However, in the anoxic-sensorimotor-restricted group, training improved stride length only. Three weeks of treadmill training were able to improve stride length in restricted and anoxic-restricted animals, although body weight deficit and the degree of degradation in muscle histology were reduced only in the restricted group.
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Parálisis Cerebral , Músculo Esquelético/patología , Condicionamiento Físico Animal/métodos , Caminata/fisiología , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Conducta Animal , Peso Corporal , Parálisis Cerebral/etiología , Parálisis Cerebral/patología , Parálisis Cerebral/rehabilitación , Modelos Animales de Enfermedad , Prueba de Esfuerzo , Femenino , Masculino , Embarazo , Ratas , Ratas Wistar , Restricción Física/métodosRESUMEN
The purpose of the current study was to investigate whether locomotor stimulation training could have beneficial effects on spinal cord plasticity consequent to sensorimotor restriction (SR). Male Wistar rats were exposed to SR from postnatal day 2 (P2) to P28. Control and experimental rats underwent locomotor stimulation training in a treadmill from P31 to P52. The intensity of the synaptophysin and caspase-3 immunoreaction was determined on ventral horn of spinal cord. The synaptophysin immunoreactivity was lower in the ventral horn of sensorimotor restricted rats compared to controls animals and was accompanied by an increased caspase-3 immunoreactivity. Those alterations were reversed at the end of the training period. Our results suggest that immobility affects the normal developmental process that spinal cord undergoes in early postnatal life influencing both pro-apoptotic and synapse markers. Also, we demonstrated that this phenomenon was reversed by 3 weeks of treadmill training.
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Maternal exercise is known to have beneficial effects in progeny development, but the influence of paternal exercise on the offspring still unclear. Since spermatogenesis is a continuous process, the father's life experiences can reprogram epigenetic content of the sperm and somehow interfere on offspring phenotype. This study was designed to evaluate the effects of paternal physical exercise on cognitive and physical development and on hippocampal DNA methylation levels of the offspring. Adult male Wistar rats were divided into two groups: sedentary and exercised. The exercise protocol occurred before mating and consisted of treadmill running, 5 consecutive days/week for 8 weeks (20â¯min/day). The mothers were not trained. The following developmental parameters were examined in male offspring: body growth, physical and cognitive performance, weights of adrenal glands, gonadal fat and hindlimb muscles, BDNF expression and global DNA methylation at the hippocampus. The progeny of trained and sedentary fathers did not differ in relation to physical parameters and performance, spatial memory and BDNF expression. However, paternal exercise promoted a decrease in offspring´s relative gonadal fat weight and a lower percentage of global hippocampal DNA methylation compared to offspring of sedentary fathers. These results pointed to interference of male physical activity at the time of conception on adiposity and hippocampal epigenetic reprogramming of male offspring. The data reinforces that exercise does not harm the descendant's development and emphasize the benefits to include the practice of physical exercise in a healthier lifestyle of the parents. Nevertheless, future studies are necessary and should investigate further the long-effects of epigenetic mechanisms in order to elucidate the father's contribution in fetal programming.
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Metilación de ADN/fisiología , Herencia Paterna/genética , Herencia Paterna/fisiología , Animales , Peso Corporal , Cognición/fisiología , Epigénesis Genética/genética , Hipocampo/metabolismo , Hipocampo/fisiología , Masculino , Obesidad/metabolismo , Condicionamiento Físico Animal/fisiología , Ratas , Ratas WistarRESUMEN
Several evidences suggest that the posterodorsal medial amygdala (MePD) can be a relevant part of the rat neural circuitry for the regulation of hypothalamic neuroendocrine secretion and for ontogenetically different behavioral displays. The dendritic spine density of Golgi-impregnated neurons from the MePD was evaluated in young rats following acute or chronic restraint stress and in aged animals (24 months old). Compared to the control group, a single 1 h restraint stress session promoted a decreased spine density (p<0.01) whereas a single 6 h restraint stress session or daily 6-h restraint sessions for 28 consecutive days did not lead to the same effect (p>0.05). Aged rats showed no difference in this dendritic spine parameter when compared to young adults (p>0.05). These results indicate that short-term stress (1 h) can affect MePD dendritic spines and that neural plasticity is involved with adaptive responses onwards in restrained rats. On the other hand, brain structural modifications related with ageing appear not to influence the number of certain postsynaptic sites in the MePD of rats.
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Envejecimiento/patología , Amígdala del Cerebelo/patología , Espinas Dendríticas/patología , Estrés Psicológico/patología , Adaptación Fisiológica/fisiología , Amígdala del Cerebelo/fisiopatología , Amígdala del Cerebelo/ultraestructura , Animales , Espinas Dendríticas/ultraestructura , Hipotálamo/metabolismo , Hipotálamo/fisiopatología , Masculino , Vías Nerviosas/fisiopatología , Plasticidad Neuronal/fisiología , Sistemas Neurosecretores/patología , Sistemas Neurosecretores/fisiopatología , Sistemas Neurosecretores/ultraestructura , Ratas , Ratas Wistar , Restricción Física , Estrés Psicológico/fisiopatologíaRESUMEN
Several physiotherapy approaches are used with different aims in the treatment of cerebral palsy (CP), such as the early stimulation and the locomotor training, but their biological effects, isolated or combined, are not completely known. In animals models, these strategies can be compared, with due translational restrictions, to the environmental enrichment (EE), that involves the enhancement of animal's physical and social environment, and locomotor stimulation (LS), that can be performed using the treadmill adapted for rats. This study was designed to describe which biological and functional mechanisms underlying rehabilitative process in clinical practice. Male rat pups were initially divided in two groups: control (healthy) and submitted to a CP model. Then, pups were divided in eight groups: CP, CPEE, CPLS, CPEELS and its respectively control groups. Functional outcomes were assessed at the postnatal day (P) 31 and P52. The tibialis anterior and soleus muscles, tibia bone parameters, the expression of synaptophysin in the primary motor cortex (M1) and ventral horn (VH) of the spinal cord, were evaluated. The association of therapies was able to improve the functional assessments and musculoskeletal parameters. Isolated therapies presented complementary benefits in CP, but the association of therapies proved to be a fundamental and effective strategy to functional recovery, besides alter positively all biological tissues evaluated in this study.
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Parálisis Cerebral/fisiopatología , Parálisis Cerebral/terapia , Ambiente , Terapia por Ejercicio , Caminata/fisiología , Animales , Parálisis Cerebral/patología , Modelos Animales de Enfermedad , Vivienda para Animales , Inmunohistoquímica , Masculino , Corteza Motora/metabolismo , Corteza Motora/patología , Destreza Motora/fisiología , Músculo Esquelético/patología , Tamaño de los Órganos , Ratas Wistar , Médula Espinal/metabolismo , Médula Espinal/patología , Sinaptofisina/metabolismo , Tibia/patologíaRESUMEN
The rat posterodorsal medial amygdala (MePD) is a component of the neural network that modulates male sexual behavior. Dendritic spines were counted in Golgi-impregnated bitufted and stellate neurons and from cells located in the medial and lateral MePD subregions. It was also studied the effect of 8-OH-DPAT, a 5-HT1A receptor agonist, microinjected into the MePD on male sexual behavior. There were no significant differences in the dendritic spine density obtained from multipolar bitufted and stellate neurons (n = 48 cells in each group; p > 0.05) or in the data from the medial or the lateral MePD (n = 48 neurons per region; p > 0.05). Rats were stereotaxically microinjected into the MePD with saline (0.2 microl, n = 6) or 8-OH-DPAT (0.1 and 1.0 microg/0.2 microl, n = 6 and 5, respectively). Behavioral recordings prior to surgery and "non-target" microinjections served as additional control data. 8-OH-DPAT 1.0 microg decreased the latencies to intromission and ejaculation, the postejaculatory refractory period and the mount frequency when compared to control pre-surgery data (p < 0.05). When compared among groups, 8-OH-DPAT 1.0 microg promoted the highest percentage reduction in the postejaculatory refractory period. Saline and injections in the vicinity of MePD did not promote relevant effects on ejaculation (p > 0.05). Results indicate that a similar dendritic spine density can be found in morphologically different populations of MePD neurons and, 8-OH-DPAT can facilitate male sexual behavior by acting on postsynaptic 5-HT1A receptors in this brain area.
Asunto(s)
8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Espinas Dendríticas/fisiología , Espinas Dendríticas/ultraestructura , Conducta Sexual Animal/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Forma de la Célula/fisiología , Espinas Dendríticas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Eyaculación/efectos de los fármacos , Eyaculación/fisiología , Femenino , Masculino , Vías Nerviosas/citología , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Receptor de Serotonina 5-HT1A/metabolismo , Serotonina/metabolismo , Agonistas de Receptores de Serotonina/farmacología , Caracteres Sexuales , Conducta Sexual Animal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Sinapsis/fisiología , Sinapsis/ultraestructura , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiologíaRESUMEN
Cerebral palsy (CP) results from nonprogressive lesions in the immature brain generating changes on the neuromuscular system. Environmental enrichment (EE) is a combination of stimuli that provides greater motivation and interest in novel movement exploration through the provision of various devices associated to enhanced social stimulation that would mimic the physiotherapy approach. The aim of this study was to verify whether EE is able to prevent the establishment of motor impairment in a CP rat model. The animals were divided in two groups: control animals (healthy) and animals submitted to a CP model. After this, the pups were exposed to two environments: enriched or standard, totaling four groups: Control group (without CP in a standard environment), CP group (CP model in a standard environment), EE group (without CP in an enriched environment) and CP-EE (CP model in an enriched environment). The experimental model was induced in pregnant Wistar rats by the association of maternal exposure to bacterial endotoxin, perinatal anoxia and sensorimotor restriction of the pups. The assessment of motor skills was held using the following tests: open field, rotarod, horizontal ladder, narrow suspended bar and stride length. The histological analysis evaluated the mean cross-sectional area (CSA) of the soleus muscle fibers, the mean CSA of motoneuronal somata and expression of synaptophysin in the ventral horn of the spinal cord. EE was able to prevent the motor deficits, however, it did not reverse the muscle atrophy observed in CP animals. Furthermore, there was an average increase in the mean area of motoneurons and an increase in the expression of synaptophysin in the ventral horn of the spinal cord of the CP-EE group in relation to CP animals reared in a standard environment. Hereupon, the stimulus increment provided by EE can prevent the onset of motor deficits and histological changes in a CP rat model.