The combined action of lead and physical load in a subchorionic experiment on rats

Introduction. Exposure to lead associated with working conditions (especially in mining and metallurgical production) is usually combined with muscular work. However, the influence of this combination on the pathological process development has not been thoroughly studied. Materials and methods. During six weeks, white outbred male rats received intraperitoneal lead acetate at a dose of 11 mg / kg, corresponding to 1/20 LD50, three times a week and/or five times a week physical exercises (forced running for 10 minutes at a speed of 25 m/min). Results. As can be seen from the results, lead caused statistically significant shifts in 33.5% of the organism’s status indices, pointing to the onset of a moderate subchronic intoxication. Content of coproporphyrin in urine and percentage of reticulocytes in the peripheral blood increased, the average content of haemoglobin in the erythrocyte decreased. Under physical activity the harmful effect of lead enhanced in 23.7% of indices and weakened in 28.9% of indices. We did not find changes in 47.4% of indices. Conclusion. Lead intoxication changes ambiguously under the influence of physical exercises. The type of combined effect of lead toxicity and physical activities depends on the outcome by which this type is assessed, on this outcome’s level and the dose ratio.

Interactive Effects of Enalapril Administration and Novel HIIT Wheel-Bed Training in Aged Rats

Introduction: Growing research suggests that aerobic high-intensity interval training (HIIT) improves cardiovascular function and physical performance compared with moderate intensity continuous training (MICT). However relatively few animal models of HIIT are available to inform about the benefits of this exercise—particularly among older animals. In addition, there is little evidence for how HIIT training interacts with adjuvant pharmacological therapies known to enhance the impact of MCIT in older individuals such as Angiotensin Converting Enzyme (ACE) Inhibitors.Purpose: The aim of the present study was to establish a HIIT protocol in aged rats based on forced running wheel-bed, and to subsequently (1) establish the feasibility of the HIIT protocol in a proof-of-concept study evaluating interactions between HIIT and (2) the result of combining HIIT + ACE inhibitor treatment using the ACE inhibitor enalapril.Methods: Two groups of rats were used in this study. The feasibility of using wheel-bed for HIIT training was tested in group one (15- and 30-month-old male rats). In the second group, 37 24-month-old Fisher 344 x Brown Norway male rats were randomly divided into four subgroups: control, enalapril, HIIT training group, and HIIT training combined with enalapril administration. The training and administration lasted for 4 weeks. After the intervention, locomotor activity, exercise tolerance, and grip strength were tested.Results: Our feasibility study suggested that middle-aged and aged rats were able to successfully complete the HIIT training. In our intervention study, HIIT training alone, regardless of adjuvant enalapril intervention, did raise treadmill exercise tolerance vs. the sedentary condition. Measures of healthspan were not negatively impacted by HIIT training.Conclusion: The novel HIIT protocol based on forced running wheel-bed was successfully employed in aged rats. We conclude that future studies should compare the results and of multi-modal intervention strategies which include both HIIT and MICT in combination with adjuvant therapies such as enalapril to improve exercise tolerance and other global indices of healthspan.

A Handful of Details to Ensure the Experimental Reproducibility on the FORCED Running Wheel in Rodents: A Systematic Review

A well-documented method and experimental design are essential to ensure the reproducibility and reliability in animal research. Experimental studies using exercise programs in animal models have experienced an exponential increase in the last decades. Complete reporting of forced wheel and treadmill exercise protocols would help to ensure the reproducibility of training programs. However, forced exercise programs are characterized by a poorly detailed methodology. Also, current guidelines do not cover the minimum data that must be included in published works to reproduce training programs. For this reason, we have carried out a systematic review to determine the reproducibility of training programs and experimental designs of published research in rodents using a forced wheel system. Having determined that most of the studies were not detailed enough to be reproducible, we have suggested guidelines for animal research using FORCED exercise wheels, which could also be applicable to any form of forced exercise.

Dopaminergic Modulation of Forced Running Performance in Adolescent Rats: Role of Striatal D1 and Extra-striatal D2 Dopamine Receptors

Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental exercise test, in which the speed was gradually increased until exhaustion. We found that systemic administration of D1-like (SCH23390) and/or D2-like (raclopride) receptor antagonists prior to the incremental test reduced the duration of forced running in a dose-dependent manner. Similarly, locomotor activity in the open field was decreased by the dopamine antagonists. Interestingly, this was not the case following intrastriatal infusion of an effective dose of SCH23390, which decreased motor performance during the incremental test without disrupting the behavioral response in the open field. Surprisingly, intrastriatal delivery of raclopride failed to impact the duration of forced running. Altogether, these results indicate that the level of locomotor response to incremental loads of forced running in adolescent rats is dopamine dependent and mechanistically linked to the activation of striatal D1 and extra-striatal D2 receptors.

Forced running exercise mitigates radiation-induced cognitive deficits via regulated DNA hydroxymethylation

Aim: Roles of forced running exercise (FE) in remediation of neurogenesis inhibition and radiation-induced cognitive dysfunction were investigated in a whole-brain irradiation mice model via the regulation of DNA 5-hydroxymethylation modification (5 hmC) and its catalytic enzymes ten–eleven translocation (Tet) proteins. Materials & methods: Hippocampal neurogenesis and cognitive function, DNA 5 hmC level and Tet expression were determined in mice. Results: The expression of DNA 5 hmC and Tet2, brain-derived neurotrophic factor significantly decreased in hippocampus postradiation. FE mitigated radiation-induced neurogenesis deficits and cognitive dysfunction. Furthermore, FE increased 5 hmC and brain-derived neurotrophic factor expression. SC1, a Tet inhibitor, reversed partly such changes. Conclusion: Tet-mediated 5 hmC modification represents a kind of diagnostic biomarkers of radiation-induced cognitive dysfunction. Targeting Tet-related epigenetic modification may be a novel therapeutic strategy for radiation-induced brain injury.