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.

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.

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.

Implications of olfactory lamina propria transplantation on hyperreflexia and myelinated fiber regeneration in rats with complete spinal cord transection.

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.

Prenatal stress produces social behavior deficits and alters the number of oxytocin and vasopressin neurons in adult rats.

The present study investigated the long-lasting effects of prenatal repeated restraint stress on social behavior and anxiety, as well as its repercussions on oxytocin (OT) and vasopressin (VP)-positive neurons of the paraventricular (PVN) and supraoptic (SON) nuclei from stressed pups in adulthood. Female Wistar rats were exposed to restraint stress in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatally non-stressed offspring raised by prenatally non-stressed mothers (NS:NS), prenatally non-stressed offspring raised by prenatally stressed mothers (S:NS), prenatally stressed offspring raised by prenatally non-stressed mothers (NS:S), prenatally stressed offspring raised by prenatally stressed mothers (S:S). As adults, male prenatally stressed offspring raised both by stressed mothers (S:S group) and non-stressed ones (NS:S group) showed impaired social memory and interaction. In addition, when both adverse conditions coexisted (S:S group), increased anxiety-like behavior and aggressiveness was observed in association with a decrease in the number of OT-positive magnocellular neurons, VP-positive magnocellular and parvocellular neurons of the PVN. The NS:S group exhibited a reduction in the amount of VP-positive magnocellular neurons compared to the S:NS. Thus, the social behavior deficits observed in the S:S and NS:S groups may be only partially associated with these alterations to the peptidergic systems. No changes were shown in the OT and VP cellular composition of the SON nucleus. Nevertheless, it is clear that a special attention should be given to the gestational period, since stressful events during this time may be related to the emergence of behavioral impairments in adulthood.

Diabetes increases mechanical sensitivity and causes morphological abnormalities in the sural nerve that are prevented by treadmill training.

INTRODUCTION: In this investigation we evaluated the effects of treadmill training on mechanical sensitivity and sural nerve morphology in diabetic rats. METHODS: Rats were divided into 3 groups: control (C); diabetic (D); and trained diabetic (TD). Training was performed for 8 weeks. Mechanical sensitivity was evaluated using von Frey filaments. Sural nerve analysis included fiber area, diameter, density of myelinated fibers, area occupied by connective tissue, myelin sheath thickness, and g-ratio. RESULTS: Animals in the D group had a reduced mechanical sensitivity threshold. Morphometric study showed that the D group had a smaller myelinated fiber area and diameter, higher density of fibers and area occupied by connective tissue, thinner myelin sheath, and higher g-ratio. The D group had a higher percentage of small myelinated fibers and a lower percentage of large-diameter myelinated fibers than the C and TD groups. CONCLUSION: Training prevents functional and morphological abnormalities in the sural nerve caused by diabetes.

General morphology and innervation of the midgut and hindgut of Megalobulimus abbreviatus (Gastropoda, Pulmonata).

We describe the morphology and innervation of the midgut and hindgut of the giant land snail Megalobulimus abbreviatus for the first time. The midgut (stomach and intestine) and hindgut (rectum and anus) are innervated by the subesophageal ganglia, through the gastrointestinal branch (originated from the visceral nerve) and the rectum-anal nerve, respectively. Backfilling through these nerves revealed neuronal bodies, mainly in the right parietal and visceral ganglia. The enteric plexuses of the midgut and hindgut are formed by extensive axonal networks and several neuronal somata arranged in clusters or as isolated cells. The gastrointestinal branch and the rectum-anal nerve directly innervate the enteric plexuses of the intestine and the hindgut, respectively. However, the outer wall of the stomach has a stomatogastric nervous system, which consists of four ganglia: stomatogastric, gastric, cardic, and pyloric. Fibers of the gastrointestinal branch project to these ganglia. Anterograde tracing from stomatogastric system ganglia revealed that the enteric plexus of the stomach is innervated only by these peripheral ganglia. Anterograde tracing of the gastrointestinal branch did not result in labeling in the enteric plexus of the stomach. Therefore, the midgut and hindgut of M. abbreviatus is controlled by an intrinsic innervation, constituted by the submucous and myenteric plexuses, which are innervated directly by neurons from the subesophageal ganglia or indirectly via the stomatogastric nervous system (for the stomach).

Exercise improves motor deficits and alters striatal GFAP expression in a 6-OHDA-induced rat model of Parkinson's disease.

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.

Effects of chronic guanosine treatment on hippocampal damage and cognitive impairment of rats submitted to chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion contributes to a cognitive decline related to brain disorders. Its experimental model in rats is a permanent bilateral common carotid artery occlusion (2VO). Overstimulation of the glutamatergic system excitotoxicity due to brain energetic disturbance in 2VO animals seems to play a pivotal role as a mechanism of cerebral damage. The nucleoside guanosine (GUO) exerts extracellular effects including antagonism of glutamatergic activity. Accordingly, our group demonstrated several neuroprotective effects of GUO against glutamatergic excitotoxicity. Therefore, in this study, we evaluated a chronic GUO treatment effects in rats submitted to 2VO. We evaluated the animals performance in the Morris water maze and hippocampal damage by neurons and astrocytes immunohistochemistry. In addition, we investigated the cerebrospinal fluid (CSF) brain derived neurotrophic factor (BDNF) and serum S100B levels. Additionally, the purine CSF and plasma levels were determined. GUO treatment did not prevent the cognitive impairment promoted by 2VO. However, none of the 2VO animals treated with GUO showed differences in the hippocampal regions compared to control, while 20% of 2VO rats not treated with GUO presented loss of pyramidal neurons and increased glial labeling cells in CA1 hippocampal region. In addition, we did not observe differences in CSF BDNF nor serum S100B levels among the groups. Of note, both the 2VO surgery and GUO treatment changed the purine CSF and plasma profile. In conclusion, GUO treatment did not prevent the cognitive impairment observed in 2VO animals, but our data suggest that GUO could be neuroprotective against hippocampal damage induced by 2VO.

The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

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.

Exercise training improves the soleus muscle morphology in experimental diabetic nerve regeneration.

INTRODUCTION: In this study we evaluate the effects of exercise training (10 weeks) on soleus muscle morphology in diabetic nerve regeneration after injury by sciatic nerve crush. METHODS: Wistar rats were assigned to either a non-diabetic (n = 6), non-diabetic injured (n = 6), diabetic (n = 6), diabetic injured (DC; n = 9), or trained diabetic injured group (TDC; n = 7). Muscle transverse sections were used for morphometric and ultrastructural analyses. RESULTS: Higher fiber density and smaller average myofiber area were observed in the DC and TDC (P < 0.05) groups compared with the other groups. This atrophic pattern was partially reversed in TDC. There was misalignment of the sarcomeres and structural alterations in the blood vessels, sarcolemma, nucleus, and mitochondria in the DC animals. The myofibers and blood vessels had a similar normal appearance in the TDC group. In addition, polyribosomes, rough sarcoplasmic reticulum, developed Golgi apparatus, and new myofibrils were observed. CONCLUSIONS: Sciatic nerve injury was found to promote soleus muscle atrophy and ultrastructural alterations in experimental diabetic nerve regeneration, which were partially reversed by exercise training.

Balance and coordination training after sciatic nerve injury.

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.

Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats.

Type 1 diabetes mellitus (T1DM) is associated with neurocognitive dysfunction and astrogliosis. Physical exercise prevents cognitive impairments and induces important brain modifications. The aim of our study was to investigate the effect of treadmill exercise on spatial memory and astrocytic function in the hippocampus of a T1DM model. Fifty-seven Wistar rats were divided into four groups: trained control (TC) (n = 15), non-trained control (NTC) (n = 13), trained diabetic (TD) (n = 14) and non-trained diabetic (NTD) (n = 15). One month after streptozotocin-induced diabetes, exercise groups were submitted to 5 weeks of physical training, and then, all groups were assessed in the novel object-placement recognition task. Locomotor activity was analyzed in the open field apparatus using Any-maze software. The expression of glial fibrillary acidic protein (GFAP) and S100B in hippocampus and cerebrospinal fluid were measured using ELISA assay, and hippocampal GFAP immunoreactivity was evaluated by means of immunohistochemistry and optical densitometry. The results showed that physical exercise prevents and/or reverts spatial memory impairments observed in NTD animals (P < 0.01). Decreased locomotor activity was observed in both the NTD and TD groups when compared with controls (P < 0.05). ELISA and immunohistochemistry analyzes showed there was a reduction in GFAP levels in the hippocampus of NTD animals, which was not found in TD group. ELISA also showed an increase in S100B levels in the cerebrospinal fluid from the NTD group (P < 0.01) and no such increase was found in the TD group. Our findings indicate that physical exercise prevents and/or reverts the cognitive deficits and astroglial alterations induced by T1DM.

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.

Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin.

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.

Hippocampal alterations in rats submitted to streptozotocin-induced dementia model are prevented by aminoguanidine.

Although the exact cause of Alzheimer's disease remains elusive, many possible risk factors and pathological alterations have been used in the elaboration of in vitro and in vivo models of this disease in rodents, including intracerebral infusion of streptozotocin (STZ). Using this model, we evaluated spatial cognitive deficit and neurochemical hippocampal alterations, particularly astroglial protein markers such as glial fibrillary acidic protein (GFAP) and S100B, glutathione content, nitric oxide production, and cerebrospinal fluid (CSF) S100B. In addition, prevention of these alterations by aminoguanidine administration was evaluated. Results confirm a spatial cognitive deficit and nitrative stress in this dementia model as well as specific astroglial alterations, particularly S100B accumulation in the hippocampus and decreased CSF S100B. The hippocampal astroglial activation occurred independently of the significant alteration in GFAP content. Moreover, all these alterations were completely prevented by aminoguanidine administration, confirming the neuroprotective potential of this compound, but suggesting that nitrative stress and/or glycation may be underlying these alterations. These findings contribute to the understanding of diseases accompanied by cognitive deficits and the STZ-model of dementia.

Skilled forelimb reaching in Wistar rats: evaluation by means of Montoya staircase test.

Experimental animals have been used as models for several neurological disorders; their performance in behavioral tests is useful in determining the success of lesion repair procedures and assessing functional recovery. The staircase test is a behavioral test that consists in reaching for food inside a special box and allows for a sensitive measure of skilled reaching by each limb in an independent manner. In most laboratories in the south of Brazil, Wistar rats are used for the study of experimental stroke, hypoxia and peripheral neuropathy, but most studies with the staircase test have used other strains such as Sprague-Dawley and Long-Evans. Because skilled reaching, grasping and performance can differ among strains, the purpose of the present study was to characterize the performance of Wistar rats in the staircase test and determine the effect of median and ulnar nerve crush. Our results with Wistar rats on the staircase test showed that: similar to other strains, Wistar animals can display high performance after 2 weeks of training; the number of animals that attained the inclusion criterion increased by 10% with longer times of training; the stricter criterion of 15 pellets taken can be adopted as study inclusion criterion; the test has an unquestionable value in assessing lateralized deficits, as evidenced by the lack of performance deficit of the non-manipulated forelimb at any time point. These results extend the understanding about the performance of Wistar rats in the staircase test, which will be used for the best training and research using this strain.

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.

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.

Endurance and resistance exercise training programs elicit specific effects on sciatic nerve regeneration after experimental traumatic lesion in rats.

OBJECTIVE: To evaluate the effects of endurance, resistance, and a combination of both types of exercise training on hindlimb motor function recovery and nerve regeneration after experimental sciatic nerve lesion in rats. METHODS: Sciatic nerve crush was performed on adult male rats, and after 2 weeks of the nerve lesion, the animals were submitted to endurance, resistance, and a combination of endurance-resistance training programs for 5 weeks. Over the training period, functional recovery was monitored weekly using the Sciatic Functional Index (SFI) and histological and morphometric nerve analyses were used to assess the nerve regeneration at the end of the trainings. RESULTS: The SFI values of the endurance-trained group reached the control values from the first posttraining week and were significantly better than both the resistance-trained group at the first, second, and third posttraining weeks and the concurrent training group at the first posttraining week. At the distal portion of the regenerating sciatic nerve, the endurance-trained group showed a greater degree of the myelinated fiber maturation than the sedentary, resistance-trained, and concurrent training groups. Furthermore, the endurance-trained group showed a smaller percentage area of endoneurial connective tissue and a greater percentage area of myelinated fibers than the sedentary group. CONCLUSION: These data provide evidence that endurance training improves sciatic nerve regeneration after an experimental traumatic injury and that resistance training or the combination of 2 strategies may delay functional recovery and do not alter sciatic nerve fiber regeneration.