Whole-body vibration mediates mechanical hypersensitivity through Aß-fiber and C-fiber thermal sensation in a chronic pain model.

Whole-body vibration (WBV), which is widely used as a type of exercise, involves the use of vibratory stimuli and it is used for rehabilitation and sports performance programmes. This study aimed to investigate the effect of WBV treatment in a chronic pain model after 10 WBV sessions. An animal model (chronic pain) was applied in 60 male Wistar rats (±180 g, 12 weeks old) and the animals were treated with low intensity exercise (treadmill), WBV (vibrating platform), and a combined treatment involving both. The controls on the platform were set to a frequency of 42 Hz with 2 mm peak-to-peak displacement, g ≈ 7, in a spiral mode. Before and after the vibration exposure, sensitivity was determined. Aß-fibers-mediated mechanical sensitivity thresholds (touch-pressure) were measured using a pressure meter. C-fibers-mediated thermal perception thresholds (hot pain) were measured with a hot plate. After each session, WBV influenced the discharge of skin touch-pressure receptors, reducing mechanical sensitivity in the WBV groups (P < 0.05). Comparing the conditions "before vs. after", thermal perception thresholds (hot pain) started to decrease significantly after the third WBV session (P < 0.05). WBV decreases mechanical hyperalgesia after all sessions and thermal sensitivity after the third session with the use of WBV.

Effects of Maternal Physical Exercise on Global DNA Methylation and Hippocampal Plasticity of Rat Male Offspring.

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.

Severe Uncontrolled Maternal Hyperglycemia Induces Microsomia and Neurodevelopment Delay Accompanied by Apoptosis, Cellular Survival, and Neuroinflammatory Deregulation in Rat Offspring Hippocampus.

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.

Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring.

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.

Synaptophysin and caspase-3 expression on lumbar segments of spinal cord after sensorimotor restriction during early postnatal period and treadmill training.

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.

Paternal physical exercise demethylates the hippocampal DNA of male pups without modifying the cognitive and physical development.

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 (20 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.

The Effects of Two Different Exercise Programs on the Ultrastructural Features of the Sciatic Nerve and Soleus Muscle After Sciatic Crush.

Peripheral nerve injuries constitute a significant medical problem and the recovery is critically dependent on post-injury treatment. In this study, following sciatic nerve crush, we investigated the effects of a 4-week endurance training program (ET) and balance and coordination training program (BCT) on the ultrastructural features of the sciatic nerve and soleus muscle. The animals were randomly divided into Sham, non-trained (NT), ET, and BCT groups each of which included three animals. Ultra-thin cross and longitudinal sections (70-85 nm) were digitized and analyzed comparatively. The electron micrographic analysis of the sciatic nerve showed similar organelles features in the injury groups (myelin debris and swelling mitochondria). Nonetheless, the ET group presented better ultrastructural features as demonstrated by the greater predominance of rounded fibers and more defined organization in the myelinated axon bundles. In the soleus muscle's analyses, the injured groups demonstrated similar organelles' features (nucleus contained highly heterochromatic nuclei and smaller mitochondria). However, ET and BCT groups showed apparently enlarged myofibril cross-sectional areas and less collagen around muscle fibers, although, the ET group displayed reduced intermyofibrillar spaces and more closely aligned myofilaments when compared with the BCT group. Based on electron micrographic analysis, our findings suggest the presence of ultrastructural differences between the Sham, NT, and the trained groups. Therefore, exercise type seems to be responsible for producing some different positive features in the trained groups, while ET seems to have a more pronounced influence on the ultrastructural features of the sciatic nerve and the soleus muscle after a crush injury. Anat Rec, 300:1654-1661, 2017. © 2017 Wiley Periodicals, Inc.

Physical exercise reverses spatial memory deficit and induces hippocampal astrocyte plasticity in diabetic rats.

Physical exercise can induce brain plasticity and reduce the cognitive decline observed in type 1 diabetes mellitus (T1DM). We investigated the effects of physical exercise to prevent or reverse spatial memory deficits produced by diabetes and some biochemical and immunohistochemical changes in hippocampal astrocytes of T1DM model. In this study, 56 male Wistar rats were divided in four groups: trained control (TC), non-trained control (NTC), trained diabetic (TD) and non-trained diabetic (NTD). 27 days after streptozotocin-induced (STZ) diabetes, the exercise groups were submitted to 5 weeks of aerobic exercise. All groups were assessed in place recognition (PR) test before and after training. The glial fibrillary acidic protein (GFAP) positive astrocytes were evaluated using planar morphology, optical densitometry and Sholl's concentric circles method. Glucose and glutamate uptake, reduced glutathione (GSH) and glutamine synthetase (GS) levels were measured using biochemical assays. Our main results are: 1-Exercise reverses spatial memory impairments generated by T1DM; 2-Exercise increases GSH and GS in TC but not in TD rats; 3-Exercise increases density of GFAP positive astrocytes in the TC and TD groups and increases astrocytic ramification in TD animals. Our findings indicate that physical exercise reverses the cognitive deficits present in T1DM and induces important biochemical and immunohistochemical astrocytic changes.

Association of environmental enrichment and locomotor stimulation in a rodent model of cerebral palsy: Insights of biological mechanisms.

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.

An evaluation of aversive memory and hippocampal oxidative status in streptozotocin-induced diabetic rats treated with resveratrol.

The present study evaluated the effects of streptozotocin (STZ)-induced diabetes on aversive memory, free radical content and enzymatic antioxidant activity in the hippocampus of adult Wistar rats submitted to oral treatment with resveratrol. Animals were divided into eight groups: non-diabetic rats treated with saline (ND SAL), non-diabetic rats treated with resveratrol at a dose 5mg/kg (ND RSV 5), non-diabetic rats treated with resveratrol at a dose 10mg/kg (ND RSV 10), non-diabetic rats treated with resveratrol at a dose 20mg/kg (ND RSV 20), diabetic rats treated with saline (D SAL), diabetic rats treated with resveratrol at a dose 5mg/kg (D RSV 5), diabetic rats treated with resveratrol at a dose 10mg/kg (D RSV 10) and diabetic rats treated with resveratrol at a dose 20mg/kg (D RSV 20). The animals received oral gavage for 35days. The contextual fear conditioning task was performed to evaluate aversive-based learning and memory. The oxidative status was evaluated in the hippocampus, by measuring the free radical content - using a 2',7'-dichlorofluorescein diacetate probe - and enzymatic antioxidant activities, such as superoxide dismutase and glutathione peroxidase. Our main behavioral results demonstrated that rats from the D RSV 10 and D RSV 20 groups showed an increase in freezing behavior when compared, respectively, to the ND RSV 10 (p<0.01) and ND RSV 20 (p<0.05). Oxidative stress parameters remained unchanged in the hippocampus of all the experimental groups. In contrast to previous experimental findings, our study was unable to detect either cognitive impairments or oxidative stress in the hippocampus of the diabetic rats. We suggest additional long-term investigations be conducted into the temporal pattern of STZ-induced diabetic disruption in memory and hippocampal oxidative status, as well as the effects of resveratrol on these parameters, in a time and dose-dependent manner.

The effect of the carotenoid bixin and annatto seeds on hematological markers and nephrotoxicity in rats subjected to chronic treatment with cisplatin

ABSTRACT This study assessed the protective effect of the carotenoid bixin and annatto seeds against possible nephrotoxicity induced with a single peritoneal administration of pharmacological cisplatin in male Wistar rats. After 48 h, the blood cell differential count showed a significant reduction in neutrophil counts in rats that received a diet rich in bixin when compared to the group that received only cisplatin. The use of cisplatin led to an increase in kidney weight. The carotenoid bixin attenuated renal injury, characterized by increased polymorphonuclear infiltration. No protective effect was observed with respect to Annatto. These results demonstrate the role of toxic cisplatin and suggest that bixin affords a protective effect against cisplatin-induced nephrotoxicity in adult Wistar rats.

Physical training improves non-spatial memory, locomotor skills and the blood brain barrier in diabetic rats.

Type 1 diabetes mellitus (T1DM) progressively affects cognitive domains, increases blood-brain barrier (BBB) permeability and promotes neurovascular impairment in specific brain areas. Physical exercise, on the other hand, has beneficial effects on brain functions, improving learning and memory. This study investigated the effects of treadmill training on cognitive and motor behavior, and on the expression of proteins related to BBB integrity, such as claudin-5 and aquaporin-4 (AQP4) in the hippocampus and striatum in diabetic rats. For this study, 60 Wistar rats were divided into four groups (n=15 per group): non-trained control (NTC), trained control (TC), non-trained diabetic (NTD), trained diabetic (TD). After diabetic induction of 30 days by streptozotocin injection, the exercise groups were submitted to 5 weeks of running training. After that, all groups were assessed in a novel object-recognition task (NOR) and the rotarod test. Additionally, claudin-5 and AQP4 levels were measured using biochemical assays. The results showed that exercise enhanced NOR task performance and rotarod ability in the TC and TD animals. Diabetes produced a decrease in claudin-5 expression in the hippocampus and striatum and reduced AQP4 in the hippocampus. Exercise preserved the claudin-5 content in the striatum of TD rats, but not in the hippocampus. The reduction of AQP4 levels produced by diabetes was not reversed by exercise. We conclude that exercise improves short-term memory retention, enhances motor performance in diabetic rats and affects important structural components of the striatal BBB. The results obtained could enhance the knowledge regarding the neurochemical benefits of exercise in diabetes.

A whole body vibration perception map and associated acceleration loads at the lower leg, hip and head.

Whole-body vibration (WBV) training has become popular in recent years. However, WBV may be harmful to the human body. The goal of this study was to determine the acceleration magnitudes at different body segments for different frequencies of WBV. Additionally, vibration sensation ratings by subjects served to create perception vibration magnitude and discomfort maps of the human body. In the first of two experiments, 65 young adults mean (± SD) age range of 23 (± 3.0) years, participated in WBV severity perception ratings, based on a Borg scale. Measurements were performed at 12 different frequencies, two intensities (3 and 5 mm amplitudes) of rotational mode WBV. On a separate day, a second experiment (n = 40) included vertical accelerometry of the head, hip and lower leg with the same WBV settings. The highest lower limb vibration magnitude perception based on the Borg scale was extremely intense for the frequencies between 21 and 25 Hz; somewhat hard for the trunk region (11-25 Hz) and fairly light for the head (13-25 Hz). The highest vertical accelerations were found at a frequency of 23 Hz at the tibia, 9 Hz at the hip and 13 Hz at the head. At 5 mm amplitude, 61.5% of the subjects reported discomfort in the foot region (21-25 Hz), 46.2% for the lower back (17, 19 and 21 Hz) and 23% for the abdominal region (9-13 Hz). The range of 3-7 Hz represents the safest frequency range with magnitudes less than 1 g(*)sec for all studied regions.

Whole body vibration at different exposure frequencies: infrared thermography and physiological effects.

The aim of this study was to investigate the effects of whole body vibration (WBV) on physiological parameters, cutaneous temperature, tactile sensitivity, and balance. Twenty-four healthy adults (25.3 ± 2.6 years) participated in four WBV sessions. They spent 15 minutes on a vibration platform in the vertical mode at four different frequencies (31, 35, 40, and 44 Hz) with 1 mm of amplitude. All variables were measured before and after WBV exposure. Pressure sensation in five anatomical regions and both feet was determined using Von Frey monofilaments. Postural sway was measured using a force plate. Cutaneous temperature was obtained with an infrared camera. WBV influences the discharge of the skin touch-pressure receptors, decreasing sensitivity at all measured frequencies and foot regions (P ≤ 0.05). Regarding balance, no differences were found after 20 minutes of WBV at frequencies of 31 and 35 Hz. At 40 and 44 Hz, participants showed higher anterior-posterior center of pressure (COP) velocity and length. The cutaneous temperature of the lower limbs decreased during and 10 minutes after WBV. WBV decreases touch-pressure sensitivity at all measured frequencies 10 min after exposure. This may be related to the impaired balance at higher frequencies since these variables have a role in maintaining postural stability. Vasoconstriction might explain the decreased lower limb temperature.

Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory Response.

Stroke is the major cause of death and the most frequent cause of disability in the adult population worldwide. Guanosine plays an important neuroprotective role in several cerebral ischemic models and is involved in the modulation of oxidative responses and glutamatergic parameters. Because the excessive reactive oxygen species produced during an ischemic event can trigger an inflammatory response, the purpose of this study was to evaluate the hypothesis that guanosine is neuroprotective against focal cerebral ischemia, inhibits microglia/macrophages activation, and mediates an inflammatory response ameliorating the neural damage. Permanent focal cerebral ischemia was induced in adult rats, and guanosine was administered immediately, 1, 3, and 6 h after surgery. Twenty-four hours after ischemia, the asymmetry scores were evaluated by the cylinder test; neuronal damage was evaluated by Fluoro-Jade C (FJC) staining and propidium iodide (PI) incorporation; microglia and immune cells were evaluated by anti-Iba-1 antibody; and inflammatory parameters such as interleukins (IL): IL-1, IL-6, IL-10; tumor necrosis factors alpha (TNF-α); and interferon-gamma (INF-γ) were evaluated in the brain tissue and cerebrospinal fluid. The ischemic event increased the levels of Iba-1-positive cells and pro-inflammatory cytokines and decreased IL-10 levels (an anti-inflammatory cytokine) in the lesion periphery. The guanosine treatment attenuated the changes in these inflammatory parameters and also reduced the infarct volume, PI incorporation, and number of FJC-positive cells, improving the functional recovery. Thus, guanosine may have been a promising therapeutic agent for the treatment of ischemic brain injury by reduction of inflammatory process triggered in an ischemic event.

Resveratrol prevents akinesia and restores neuronal tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta of diabetic rats.

This study evaluated the effects of resveratrol on locomotor behaviors, neuronal and glial densities, and tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta of rats with streptozotocin-induced diabetes. Animals were divided into four groups: non-diabetic rats treated with saline (SAL), non-diabetic rats treated with resveratrol (RSV), diabetic rats treated with saline (DM) and diabetic rats treated with resveratrol (DM+RSV). The animals received oral gavage with resveratrol (20 mg/kg) for 35 days. The open field test and the bar test were performed to evaluate bradykinesia and akinesia, respectively. The Nissl-stained neuronal and glial densities and the dopaminergic neuronal density were estimated using planar morphometry. Tyrosine hydroxylase immunoreactivity was evaluated using regional and cellular optical densitometry. In relation to the locomotor behaviors, it was observed that the DM group developed akinesia, which was attenuated by resveratrol in the DM+RSV group, while the DM and DM+RSV groups showed bradykinesia. Our main morpho-physiological results demonstrated: a decrease in the cellular tyrosine hydroxylase immunoreactivity in the DM group, which was attenuated by resveratrol in the DM+RSV group; a higher neuronal density in the RSV group, when compared to the DM and DM+RSV groups; an increase in the glial density in the DM group, which was also reversed by resveratrol in the DM+RSV group. Resveratrol treatment prevents akinesia development and restores neuronal tyrosine hydroxylase immunoreactivity and glial density in the substantia nigra pars compacta of diabetic rats, suggesting that this polyphenol could be a potential therapeutic option against diabetes-induced nigrostriatal dysfunctions.

Beneficial effects of early environmental enrichment on motor development and spinal cord plasticity in a rat model of cerebral palsy.

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.

Enriched environment induces beneficial effects on memory deficits and microglial activation in the hippocampus of type 1 diabetic rats.

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.

Physical exercise increases GFAP expression and induces morphological changes in hippocampal astrocytes.

Physical exercise has an important influence on brain plasticity, which affects the neuron-glia interaction. Astrocytes are susceptible to plasticity, and induce and stabilize synapses, regulate the concentration of various molecules, and support neuronal energy metabolism. The aim of our study was to investigate whether physical exercise is capable of altering the morphology, density and expression of glial fibrillary acidic protein (GFAP) in astrocytes from the CA1 region of rat hippocampus. Thirteen male rats were divided in two groups: sedentary (n = 6) and exercise (n = 7). The animals in the exercise group were submitted to a protocol of daily physical exercise on a treadmill for four consecutive weeks. GFAP immunoreactivity was evaluated using optical densitometry and the morphological analyses were an adaptation of Sholl's concentric circles method. Our results show that physical exercise is capable of increasing the density of GFAP-positive astrocytes as well as the regional and cellular GFAP expression. In addition, physical exercise altered astrocytic morphology as shown by the increase observed in the degree of ramification in the lateral quadrants and in the length of the longest astrocytic processes in the central quadrants. Our data demonstrate important changes in astrocytes promoted by physical exercise, supporting the idea that these cells are involved in regulating neural activity and plasticity.

Análise morfométrica do nervo isquiático de ratos Wistar adultos submetidos à compressão crônica através de um clipe cirúrgico / Morphometric analysis of the sciatic nerve of Wistar rats submitted to chronic compression through surgical clip

Introdução: Hiperidrose é uma condição idiopática caracterizada por sudorese excessiva generalizada ou restrita a extremidades. O tratamento definitivo e com menor morbidade é a simpatectomia videotoracoscópica. O bloqueio da cadeia simpática com clipe possibilitaria a reversão da cirurgia para pacientes que sofrem de hiperidrose compensatória pós-operatória ­ complicação mais problemática. Como objetivo, este trabalho visa analisar a arquitetura ultraestrutural e morfométrica do nervo isquiático de ratos Wistar machos adultos submetidos à compressão crônica através de um clipe cirúrgico. Os objetivos são identificar se há alteração nervosa com o clipamento e se existe tempo para promover o retorno às atividades neuronais pós-retirada do clipe. Pode-se, portanto, verificar se o clipamento é eficaz como forma de tratamento para hiperidrose, com a vantagem de ser um procedimento reversível. Métodos: Foram selecionados 30 ratos Wistar machos separados em 3 grupos ­ 1, 2 e 3 ­ com n=10, com a retirada do clipe em 1, 2 e 4 semanas, respectivamente. Cada grupo foi dividido em A e B com n=5. Todos os ratos do grupo A eram sacrificados no momento da retirada do clipe e, no B, uma semana após a retirada do clipe. Resultados: O estudo mostrou que, em cada um dos grupos, houve nervos normais e com degeneração, independentemente da retirada do clipe ou de sua manutenção. Conclusão: Simpatectomia com clipe parece não ser um bom método para o tratamento da hiperidrose. O efeito da simpatectomia com clipe e sua remoção devem ser melhor observados em grandes estudos (AU)

Introduction: Hyperhidrosis is an idiopathic condition characterized by excessive sweating that may be generalized or restricted to specific parts of the body. The definitive treatment with less morbidity is endoscopic thoracic sympathectomy. Blockade of the sympathetic chain with a clip enables reversal of surgery for patients suffering from postoperative compensatory sweating ­ the most problematic complication. This work was designed to assess the ultrastructural and morphometric architecture of the sciatic nerve of adult male Wistar rats subjected to chronic compression via surgical clip. The aims were to determine if there are changes to nerve from clipping and if there is time to restore neuronal activity after removal of the clip. One can thus check if clipping is an effective treatment for hyperhidrosis, with the advantage of being a reversible procedure. Methods: Thirty male Wistar rats were selected and divided into 3 groups of ten rats each, with removal of the clip at weeks 1, 2 and 4, respectively. Each group was divided into A and B with n = 5. Rats in group A were sacrificed at the time of clip withdrawal and rats in group B were sacrifi ced one week after clip withdrawal. Results: The study showed that, in each of the groups, there were normal and degenerated nerves regardless of clip removal or maintenance. Conclusion: Sympathectomy with clip does not seem to be a good method for the treatment of hyperhidrosis. The effect of sympathectomy with clip and its removal should be further investigated in larger studies (AU)