Untrained Rats Research Articles

Setting Treadmill Intensity for Rat Aerobic Training Using Lactate and Gas Exchange Thresholds.

To open up new horizons of translational research, we studied the lactate threshold (LT)-dependent physiological responses and adaptations to exercise in rats, highlighting the importance of intensity-specific studies for optimizing exercise prescriptions. LT is physiologically related to the non-invasive gas exchange threshold (GET), and both thresholds are moderate-heavy-intensity boundary indices in determining an effective intensity of aerobic training in humans. While their practical utility is presumed to extend to rats, the actual existence of GET, the thresholds' relations to maximal oxygen consumption (VO2max), and whether aerobic adaptations by training differ around the LT intensity remain uncertain. This study sought to identify the GET using our previously established rat LT-model by combining the use of a metabolic chamber and the V-slope method and to confirm the thresholds' relations to VO2max. We investigated changes in the thresholds and VO2max following 6 weeks of endurance training at below or above LT intensity. GET and LT were significantly correlated, and agreed with high precision, although with a fixed bias. Untrained rats exhibited GET and LT at 56% and 52% of their VO2max, respectively. Endurance training at supra-, but not below-, the LT intensity significantly improved VO2max and both thresholds; however, their %VO2max remained unaltered. GET in rats is identifiable as a threshold associated with LT using the V-slope method. Further, both thresholds can serve as moderate-heavy-intensity boundary indices for the aerobic training of rats. This study advances our understanding of exercise intensity regulation in rats, thereby contributing to the development of a more nuanced and effective model for exercise prescription, with implications for human health and fitness.

Enhancement of response learning in male rats with intrastriatal infusions of a BDNF - TrkB agonist, 7,8-dihydroxyflavone.

Enhancement of learning and memory by cognitive and physical exercise may be mediated by brain-derived neurotrophic factor (BDNF) acting at tropomyosin receptor kinase B (TrkB). Upregulation of BDNF and systemic administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), enhance learning of several hippocampus-sensitive tasks in rodents. Although BDNF and 7,8-DHF enhance functions of other brain areas too, these effects have mainly targeted non-cognitive functions. One goal of the present study was to determine whether 7,8-DHF would act beyond the hippocampus to enhance cognitive functions sensitive to manipulations of the striatum. Here, we examined the effects of intrastriatal infusions of 7,8-DHF on learning a striatum-sensitive response maze and on phosphorylation of TrkB receptors in 3-month-old male Sprague Dawley rats. Most prior studies of BDNF and 7,8-DHF effects on learning and memory have administered the drugs for days to months before assessing effects on cognition. A second goal of the present study was to determine whether a single drug treatment near the time of training would effectively enhance learning. Moreover, 7,8-DHF is often tested for its ability to reverse impairments in learning and memory rather than to enhance these functions in the absence of impairments. Thus, a third goal of this experiment was to evaluate the efficacy of 7,8-DHF in enhancing learning in unimpaired rats. In untrained rats, intrastriatal infusions of 7,8-DHF resulted in phosphorylation of TrkB receptors, suggesting that 7,8-DHF acted as a TrkB agonist and BDNF mimic. The findings that a single, intra-striatal infusion of 7,8-DHF 20 min before training enhanced response learning in rats suggest that, in addition to its trophic effects, BDNF modulates learning and memory through receptor mediated cell signaling events.

Impact of dihydropyrimidinase-related protein 2 in memory formation on rats and its possible role in neuronal back remodeling

The article concerns the problem of molecular mechanisms of memory formation. In this study the effects of polyclonal antibodies to serotonin-modulating anticonsolidation protein (SMAP) complex and its component dihydropyrimidinase-related protein 2 (DRP2) have been analyzed. Intra-cerebral administration of polyclonal anti-SMAP antibody significantly enhanced elaboration and strengthened memory formation in two complex behavioral conditioned models. At the same time, intra-cerebral administration of anti-SMAP antibody resulted in an increase of the content of nerve growth factor (NGF) in the water-soluble fraction of the hippocampus while intra-cerebral administration of anti-DRP2 antibody caused a decrease in the content of β-III tubulin (a marker of differentiated neurons) in the hippocampus and in the left parietal cortex of untrained rats. The obtained results indicate that DRP2 might participate in regulation of the processes of back remodeling of mature nerve cells of adult organisms, occurring during training of rats in the behavioral paradigm used in this study under the effects of anti-SMAP and anti-DRP2 antibodies. Conclusion is made that back remodeling (dedifferentiation) of mature nerve cells, apparently, is engaged in memory formation.

Protocol guide for food foraging behavior test: Assessment of decision making in rodents

Food foraging behavior requires higher cognitive function like investing efforts in decision making. Hoarding food for the future consumption in adverse climatic conditions or to avoid predatory threats needs precise perception and potential of decision making to overcome challenges in the time of need. The brain areas and neural circuitry responsible for such cognitive skills are poorly understood. Previously available animal models are trained prior to test, which makes it difficult to understand the true nature of animals, and hoard the food from external source into the cage. The new food foraging behavior test, recently developed and evidenced by Li et al., relies on untrained rats and test the competitive ability and hoarding from source within the test box. It can be used to study decision making potentials and underlying neural bases in laboratory settings. Multiple aspects like food quality/flavor preference, competitive nature can be assessed within the test box and the paradigm is conveniently customizable according the hypothesis. However, a detailed protocol guide, to be followed in the laboratory setting, for food foraging behavior test is not available. Therefore, it is urged to produce an elaborated guide for scientists to conduct food foraging behavior test in convenient and precise manner.

Lactate thresholds and role of nitric oxide in male rats performing a test with forced swimming to exhaustion.

The present study assessed a complex of biochemical parameters at the anaerobic threshold (AT) in untrained male Wistar rats with different times to exhaustion (Tex ) from swimming. The first group of rats was randomly divided into six subgroups and subjected to a swimming test to exhaustion without a load or with a load of 2%-10% of body weight (BW). In the first group, we established that for untrained rats, the load of 4% BW in the swimming to exhaustion test was optimal for endurance assessment in comparison with other loads. The second group of rats went through a preliminary test with swimming to exhaustion at 4% BW and was then divided into two subgroups: long swimming time (LST, Tex > 240 min) and short swimming time (SST, Tex < 90 min). All rats of the second group performed, for 6 days, an experimental training protocol: swimming for 20 min each day with weight increasing each day. We established that the AT was 3% BW in SST rats and 5% BW in LST rats. The AT shifted to the right on the lactate curve in LST rats. Also, at the AT in the LST rats, we found significantly lower levels of blood lactate, cortisol, and NO.

Native predators can learn new prey cues to overcome naivete and hunt novel alien prey

Biological invasions continue to rise globally, increasing the frequency of novel ecological interactions and the potential for naivete. Native predators can defend against invasion by alien prey species through biotic resistance, but initial predator naivete towards novel alien prey can allow prey to establish. Here we test if predator naivete can be overcome via a learned association between novel prey cues and a food reward, and if this conditioning increases predator motivation to hunt novel alien prey. We exposed free-living native bush rats (Rattus fuscipes) to repeated bouts of novel alien cockroach (Nauphoeta cinerea) odour and food rewards over an 11-day training period. We then conducted a simulated invasion, comparing the survival rates of sentinel cockroach prey in sites with trained and untrained rats. Cockroaches in sites with trained rats were 46 % more likely to be found and consumed over the invasion period than prey in sites with untrained rats. Also, the number of food rewards taken during training was correlated with the number of prey consumed on the first night of the invasion. Our results suggest that predators can overcome their naivete to novel prey through learning and that pre-exposing free-living predators to novel prey cues can subsequently increase predation rates on novel alien prey.

Comparison of interleukin-6, oxidant and antioxidant levels in the kidneys of the trained and untrained rats following exhaustive exercise

In this study, the cytokine response (interleukin-6; IL-6), free oxygen radicals which are claimed to be responsible for the damage in the kidney tissue of exercise-trained rats and untrained-rats, and antioxidant levels were investigated after being forced to an exhausting run. Forty male Wistar albino rats were assigned to the following groups: sedentary controls (C); untrained animals that acutely completed the exhaustive exercise and were sacrificed immediately after exhaustion (UT-i) or 1 day after exhaustion (UT-1); and long-term trained animals that completed the exhaustive exercise and were sacrificed immediately after exhaustion (T-i) or 1 day after exhaustion (T-1). In UT-i and 1 day after exhaustion (T-1) groups, total oxidant status levels were increased compared to controls (P&lt;0.05). IL-6, which is reported to have an anti-inflammatory effect in exercise, did not increase in untrained group immediately, but started to increase 1 day after exhaustion compared to controls. IL-6 levels were significantly increased in the T-i and T-1 groups compared to the control and UT-i groups (P&lt;0.05). The level of total antioxidant status did not show a significant increase in the UT-i group but started to rise after exhaustion the T-1 group. IL-6 levels were significantly increased in the T-i and T-1 groups compared to the control, UT-i, and UT-1 groups (P&lt;0.05). As a result, while oxidant stress and antioxidant mechanism increased immediately in the trained group, IL-6 increased significantly immediately and 1 day later. In the untrained group, however, an increase was observed in oxidant stress, antioxidant mechanism, and IL-6 levels after 1 day.

CHANGES IN THE VOLUME OF LEFT ATRIUM IN HEALTHY WHITE EXPERIMENTAL RATS AGED 10-11 WEEKS EXERCISED WITH MODERATE INTENSITY

The aim of the study was to evaluate the volume of the left atrium by ultrasonography after dosed, moderate-intense treadmill exercise for 10 weeks in healthy rats aged 10-11 weeks. In general, physical exercise is a well-known preventive method for reducing the risk-factors of cardiovascular diseases. Within the frame of our study, we subjected 10-11-week-old healthy male rats to moderate-intensity physical exercise on treadmill for 10 weeks and then studied functional parameters of heart by echocardiography to assess the effect of physical exercise on the volume of left atrium of healthy heart. Rats were divided into 2 groups: 1) control group, which did not receive any exercise (n=6); 2) the investigational group performed 6 complete rotations on treadmill per day with a 2-minute active break in between, 5 days a week (treadmill speed 12m/min, incline 200) – n=6.The functional parameters of heart were evaluated by transthoracic echocardiography twice (at the beginning of the study and after 10 weeks). In the rats of the investigational group, the volume of the left atrium was increased compared to the data of untrained rats of the same sex and age. The mentioned study can be considered as another step forward in the study of compensative changes developed amid physical exercise with moderate intensity.

Regular exercise increases H2S levels in mitochondria and cardiac tissue, enhances genes expression of H2S-synthesizing enzymes and prevents mitochondrial swelling

Abstract Funding Acknowledgements Type of funding sources: None. Introduction It is known that regular exercise is important and very useful for the cardiovascular system because of decreasing the incidence of myocardial infarction and protection against chronic and acute coronary disease. It normalizes blood pressure, lowers weight, reduces vascular resistance and enhances structural adaptations through increasing number of capillaries and arteries. It was also shown that exercise has a positive effect on vasodilatation by increasing nitric oxide (NO) production via eNOS gene expression enhancing. As we know hydrogen sulfide (H2S) is also a gaseous molecule that performs many functions in the cardiovascular system. It was found that disorders of H2S synthesis are found during hypertension, atherosclerosis, diabetes, heart failure, neurodegenerative diseases and aging. Purpose The aim of this study was to investigate the effect of moderate exercise on endogenous H2S content, gene expression levels of H2S-synthesizing enzymes and opening of mitochondrial pore in adult and old rats. Methods We used adult (5-7 months) and old (22-24 months) Wistar male rats. Physical training of adult and old animals was carried out 5 days a week by forcibly swimming for six and four weeks, respectively. The first training session of adult and old rats lasted 2 minutes and the duration was increased by 4 and 2 minutes every other day respectively. Mitochondria were isolated by differential centrifugation method. H2S was determined in mitochondria and heart tissues by biochemical method using zinc acetate, N,N-DPD and FeCl3. H2S-synthesizing enzymes genes were defined by real-time PCR using TaqMan Master Mix and primers for CSE and 3-MST. Results In our experiments we showed that physical training increases the H2S level in mitochondria and heart tissue of adult and old animals. The concentration of H2S in mitochondria enhances by 2,3 times for adult (4,58±0,3 nmol/mg compare to 10,55 ±1,18 nmol/mg, Р&amp;lt;0,05) and by 8,8 times for old rats (2,38±0,45 nmol/mg compare to 20,91 ±3,56 nmol/mg, Р&amp;lt;0,05). A slight increase in these indicators was also observed in the heart tissue of both groups. It should be noted that in old animals initially H2S level was decreased twice compared to adult. At the same time the levels of H2S-synthesizing enzymes, CSE and 3-MST, was lowered by 4 and 3 times in old rat heart. Exercise increases levels of these genes by 2,6 and 3 times for adult cardiac tissue and 7,9 and 7,2 times for old heart tissue. Physical training also has positive effect on mitochondrial pore opening and reduces ROS generation in the heart of old animals. Thus, Ca2+-induced mitochondrial swelling decreased by 37% in adult and 26% in old rat cardiac tissue, and the rate of O2- generation by 85% compared to untrained rats. Conclusion Physical training increases H2S levels, genes expression of H2S-synthesizing enzymes in mitochondria and cardiac tissue and prevents mitochondrial permeability transition opening in adult and old rats.

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury.

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited.Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats.We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14).This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability.

Rehabilitative training improves skilled forelimb motor function after cervical unilateral contusion spinal cord injury in rats

Animal models of cervical spinal cord injury (SCI) have frequently utilized partial transection injuries to evaluate plasticity promoting treatments such as rehabilitation training of skilled reaching and grasping tasks. Though highly useful for studying the effects of cutting specific spinal tracts that are important for skilled forelimb motor function, cervical partial-transection SCI-models underappreciate the extensive spread of most human SCIs, thus offering poor predictability for the clinical setting. Conversely, moderate cervical contusion SCI models targeting the spinal tracts important for skilled reaching and grasping can better replicate the increased size of most human SCIs and are often considered more clinically relevant. However, it is unknown whether animals with moderate cervical contusion SCIs that damage key spinal motor tracts can train in skilled reaching and grasping tasks. In this study, we quantify the impact of injury size and distribution on recovery in a skilled motor task called the single pellet reaching, grasping and retrieval (SPRGR) task in rats with cervical unilateral contusion injuries (UCs), and compare to rats with a partial transection SCIs (i.e., dorsolateral quadrant transection; DLQ). We found that UCs damage key tracts important for performing skilled motor tasks, similar to DLQs, but UCs also produce more extensive grey matter damage and more ventral white matter damage than DLQs. We also compared forelimb functionality at 1, 3, and 5 weeks of rehabilitative motor training between trained and untrained rats and found a more severe drop in SPRGR performance than in DLQ SCIs. Nevertheless, despite more severe injuries and initially low SPRGR performance, rehabilitative training for contusion animals resulted in significant improvements in SPRGR performance and proportionally more recovery than DLQ rats. Our findings show that rehabilitative motor training can facilitate considerable amounts of motor recovery despite extensive spinal cord damage, especially grey matter damage, thus supporting the use of contusion or compression SCI models and showing that ventral grey and white matter damage are not necessarily detrimental to recovery after training.

High-frequency burst spiking in layer 5 thick-tufted pyramids of rat primary somatosensory cortex encodes exploratory touch

Diversity of cell-types that collectively shape the cortical microcircuit ensures the necessary computational richness to orchestrate a wide variety of behaviors. The information content embedded in spiking activity of identified cell-types remain unclear to a large extent. Here, we recorded spike responses upon whisker touch of anatomically identified excitatory cell-types in primary somatosensory cortex in naive, untrained rats. We find major differences across layers and cell-types. The temporal structure of spontaneous spiking contains high-frequency bursts (≥100 Hz) in all morphological cell-types but a significant increase upon whisker touch is restricted to layer L5 thick-tufted pyramids (L5tts) and thus provides a distinct neurophysiological signature. We find that whisker touch can also be decoded from L5tt bursting, but not from other cell-types. We observed high-frequency bursts in L5tts projecting to different subcortical regions, including thalamus, midbrain and brainstem. We conclude that bursts in L5tts allow accurate coding and decoding of exploratory whisker touch.

Extracellular levels of glucose in the hippocampus and striatum during maze training for food or water reward in male rats

Glucose potently enhances cognitive functions whether given systemically or directly to the brain. The present experiments examined changes in brain extracellular glucose levels while rats were trained to solve hippocampus-sensitive place or striatum-sensitive response learning tasks for food or water reward. Because there were no task-related differences in glucose responses, the glucose results were pooled across tasks to form combined trained groups. During the first 1−3 min of training for food reward, glucose levels in extracellular fluid (ECF) declined significantly in the hippocampus and striatum; the declines were not seen in untrained, rewarded rats. When trained for water reward, similar decreases were observed in both brain areas, but these findings were less consistent than those seen with food rewards. After the initial declines in ECF glucose levels, glucose increased in most groups, approaching asymptotic levels ∼15−30 min into training. Compared to untrained food controls, training with food reward resulted in significant glucose increases in the hippocampus but not striatum; striatal glucose levels exhibited large increases to food intake in both trained and untrained groups. In rats trained to find water, glucose levels increased significantly above the values seen in untrained rats in both hippocampus and striatum. The decreases in glucose early in training might reflect an increase in brain glucose consumption, perhaps triggering increased brain uptake of glucose from blood, as evident in the increases in glucose later in training. The increased brain uptake of glucose may provide additional neuronal metabolic substrate for metabolism or provide astrocytic substrate for production of glycogen and lactate.

The Effects of Direct Red Bull Administration to Isolated Hearts of Trained and Untrained Rats Who Regularly Consumed or Did Not Consume Energy Drink: Focus on Cardiodynamics and Oxidative Stress

Abstract Energy drinks (EDs) contain caffeine and other active ingredients which affect cardiovascular system. The aims of this study were to examine direct effects of Red Bull (RB) on cardiodynamics and oxidative stress in isolated hearts of rats. The rats were divided into four groups: untrained rats who never consumed ED (dEDUT); untrained rats who consumed ED 5 days a week during 4 weeks (ch+dED-UT); rats trained 5 times a week for 4 weeks, but did not consume ED (dED-T); rats trained and consumed ED 5 times a week for 4 weeks (ch+dED-T). After sacrificing, hearts were isolated and perfused according to Langendorff technique. Through the isolated heart of all rats in each group, RB was administered. The parameters of cardiac function were recorded, and the levels of prooxidants were measured in the coronary effluent during coronary autoregulation. Rats in ch+dED-UT group had significantly lower rates of myocardial contraction and relaxation compared to rats in dED-UT group. The same effect was recorded in the dED-T group compared to dED-UT group. The levels of hydrogen peroxide were significantly higher in trained rats. Rats in ch+dED-T group also had significantly higher levels of superoxide anion radical and index of lipid peroxidation, as well as lower levels of nitrites when compared to ch+dED-UT group, while opposite effect was recorded in rats in dED-T group compared to dEDUT group. The RB could have a potentially negative inotropic effect in chronic consumers. Prooxidative effect of RB was most pronounced in trained chronic consumers.

Вплив кальцієвого навантаження на утворення мітохондріальних пор in situ і експресію генів мітохондріальних роз’єднувальних білків у серці тренованих щурів

We have studied the effect of calcium load (1.7 to 15 mmol/l in perfusate) on isolated heart function, mitochondrial factor release (as a marker of mitochondrial permeability transition pore, MPTP), and cardiac uncoupling proteins (UCP2/3) mRNA expression in untrained and trained rats (swimming for 4 weeks). It was found that the improvement in the isolated heart function of trained rats was accompanied by an increase in the expression of UCP3, but not UCP2. A gradual increase of the calcium content in the perfusate led to an increase in contractile function, more pronounced in trained rats. However, 10 mmol/l and higher concentration of calcium led to arrhythmia and drastic decrease in contractility of isolated heart more obvious in untrained rats. Swimming course prevented the calcium-induced release of mitochondrial factor exerting a stabilizing effect on mitochondrial membranes which was, however, diminished by a nitric oxide synthesis blocker (L-NAME). We have found that UCPs genes expression is calcium-sensitive: an increase in UCP3 mRNA at 5 mmol of calcium and a sharp decrease in UCP2/3 expression at 12.5 mmol/l of calcium in perfusate in both trained and untrained rats indicating the participation of UCPs in the regulation of calcium homeostasis. Our data suggest that the calcium load may serve as a test for in situ MPTP titration. Activation of UCPs together with up-regulated nitric oxide may play a protective role against increasing extracellular calcium inhibiting MPTP formation during physical trainings.

Physiological and oxidative stress responses to intermittent hypoxia training in Sprague Dawley rats

Aim Rapid ascent to high altitude and inability to acclimatize lead to high-altitude illnesses. Intermittent hypoxia (IH) conditioning has been hypothesized as a non-pharmacological strategy aiming to improve adaptive responses during high altitude ascent. In the recent years, IH training (IHT) has become increasingly popular among recreational and professional athletes owing to its ability to mitigate high altitude related problems. This study aimed at exploring the role of IHT in altitude acclimatization. Methods Male Sprague Dawley rats were subjected to IHT for 4 h consecutively for 5 days at 12% FiO2 under normobaric conditions. To assess the effect of IHT in hypoxic acclimatization, animals were further exposed to extreme hypoxia (EH) at 8% FiO2. Oxygen saturation (SpO2), respiratory rate and heart rate were recorded during the exposure. Oxidative stress (ROS, MDA, and 4-HNE) and histopathological examinations were studied in the lung tissue sections. Hypoxia biomarkers, HIF-1α, EPO, VEGF, and BPGM were evaluated through western blotting in the lung tissue. Results Assessment of the IHT showed that SpO2 levels were found to be higher in the IH trained rats with a statistical difference of p < 0.01 in the first hour of hypoxia exposure as compared to the untrained rats. There was a significantly higher (p < 0.001) generation of ROS and MDA in the untrained rats as compared to the trained rats. Lipid peroxidation markers and systemic inflammatory marker were found to be expressed at much higher level in the untrained rats. There was a higher expression of HIF-1α (1.24-fold ↑), VEGF (1.14-fold ↑) and decrease in EPO (1.43-fold ↓) in the untrained rats as compared to trained rats. Conclusions Preconditioning with IHT resulted in the reduction in hypoxia induced oxidative stress during extreme hypoxia exposure and thus, maintaining redox balance as well as adjustment in the physiological changes in rats.

Adjustments in β-Adrenergic Signaling Contribute to the Amelioration of Cardiac Dysfunction by Exercise Training in Supravalvular Aortic Stenosis.

Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive β-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through β-adrenergic signaling preservation. Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks. ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The β2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the β-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during β-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET. Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the β-adrenergic responsiveness, which reveals that the adjustments in β-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats.

The Capability to Learn and Expression of the Insulin-Like Growth Factor II Gene in the Brain of Male Rats Whose Fathers Were Subjected to Stress Factors in the “Stress–Restress” Paradigm

Abstract—We studied the capability to learn in a passive avoidance task and the rate of its extinction in male rats whose fathers were subjected to stress during the period of spermatogenesis using the “stress–restress” paradigm (a model of post-traumatic stress disorder). In the brain of trained and untrained rats, we studied the expression of genes encoding insulin-like growth factor II and H19, the expression of which is imprinted at the early stages of ontogeny. Experimental males exhibited impaired memory consolidation and accelerated extinction of a passive avoidance response. The expression of Igf2 was decreased in the hippocampus and neocortex of untrained male offspring of stressed fathers. The increased expression of the Igf2 and H19 genes was revealed in the hippocampus of male offspring of control fathers 20 h after training, whereas in the experimental rats, the expression of these genes did not alter. Our data show that the impairment of memory in male offspring of stressed fathers may be mediated by decreased expression of the Igf2 gene.

Evaluation of the effects of different intensities of forced running wheel exercise on oxidative stress biomarkers in muscle, liver and serum of untrained rats.

Exercise induces different effects on antioxidant status depending on its intensity. The forced running wheel (FRW) model maintains a constant intensity and volume during exercise. The aim of the present study was to investigate the effects of FRW exercise at different running speeds on several serum biochemical parameters of liver and muscle functions and on oxidative stress biomarkers in skeletal muscle, liver and serum in the rat. Thirty-six male Wistar rats were randomly divided into six groups. Five groups participated in constant power tests at intensities of 10, 13, 14.5, 16, and 17.5 m/min, and a non-exercise group was chosen as the control. Serum, muscle and liver tissues were collected after the tests and analyzed. At speeds >16 m/min, exercise on an FRW significantly increased several serum biochemical parameters, malondialdehyde level and superoxide dismutase activity in all tissues of exercise rats compared with control rats; FRW exercise also increased catalase activity in the liver and glutathione S-transferase activity in muscle, whereas it decreased glutathione level in all tissues and catalase activity in muscle and serum. These data suggest that FRW exercise in rats activates an adaptation of the antioxidant system response in skeletal muscle at speeds <16 m/min, whereas it induces oxidative stress at higher speeds in muscle, liver and serum. In addition, we observed a correlation between the systematic and local oxidative stress status in rats after exercise on FRW.

Exercise Prevents Hypertension and Disrupts the Correlation Between Vascular Sympathetic Activity and Age-Related Increase in Blood Pressure in SHRs.

Hypertension usually accompanies the elevated sympathetic activity and sleep interruption. Few researches explored the dynamic changes and possible correlations in cardiovascular functions and sleep patterns during the development of hypertension. In contrast, exercise training provides several benefits on cardiovascular and sleep function in hypertensive subjects. However, controlling various factors during a long period of exercise training is difficult in hypertensive subjects, an animal model may be essential. This study aimed to explore dynamic changes in cardiovascular functions and sleep patterns during the development period of hypertension (10-20 weeks old) in spontaneously hypertensive rats (SHRs) and effects of exercise intervention. We used the treadmill exercise model for 8 weeks and started when SHRs were 12 weeks old. Electroencephalogram, electromyogram, electrocardiogram, and blood pressure (BP) were recorded simultaneously for 24 hours once a week over 11 weeks. Untrained SHRs revealed the age-related increments in BP, and the significant increasing slopes of differences on BP and vascular sympathetic activity were observed during the development period of hypertension. Compared with untrained rats, age-related increases in BP and vascular sympathetic activity were significantly suppressed in trained SHRs. Nevertheless, trained SHRs showed more quiet sleep time at partial weeks. The positive correlation between the differences from 10 weeks of vascular sympathetic activity and BP was disappeared in trained SHRs. There existed the significant correlation between the dynamic changes of vascular sympathetic activity and age-related elevation of BP during the development period of hypertension; however, exercise prevented hypertension and disrupted this correlation.