Aerobic exercise is an increasing trend worldwide. However, people are increasingly exercising outdoors, alongside roadways where heavy vehicles release diesel exhaust. We analyzed respiratory effects caused by inhaled diesel particulate emitted by vehicles adhering to Brazilian legislation, PROCONVE Phase P7 (equivalent to EURO 5), as well the effects of exposure during moderate-intensity aerobic exercise. Male C57BL/6 mice were divided into 4 groups for a 4-week treadmill protocol: CE (n=8) received intranasal sterile physiological saline and then performed moderate-intensity exercise (control), CS (n=10) received saline and then remained stationary on the treadmill (control), DS (n=9) received intranasal diesel exhaust particles and then remained stationary, and DE (n=10) was exposed to diesel exhaust and then exercised at moderate intensity. Mice were subsequently connected to a mechanical ventilator (SCIREQ{copyright, serif} flexiVent®, Canada) to analyze the following respiratory mechanics parameters: tissue resistance, elastance, inspiratory capacity, static compliance, Newtonian resistance, and pressure-volume loop area. After euthanasia, peripheral pulmonary tissue strips were extracted and subjected to force-length tests to evaluate parenchymal elastic and mechanical properties, using oscillations applied by a computer-controlled force transducer system; parameters obtained were tissue resistance, elastance, and hysteresivity. DS displayed impaired respiratory mechanics for all parameters, in comparison to CS. DE exhibited significantly reduced inspiratory capacity and static compliance, and increased Newtonian resistance when compared to CE. Exposure to diesel exhaust, both during exercise and rest, still exerts harmful pulmonary effects, even at current legislation limits. These results justify further changes in environmental standards, to reduce the health risks caused by traffic-related pollution.
Purpose: Mania is associated with disturbed dopaminergic transmission in frontotemporal regions. D-amphetamine (AMPH) causes increased extracellular DA levels, considered an acknowledged mania model in rodents. Doxycycline (DOXY) is a second-generation tetracycline with promising neuroprotective properties. Here, we tested the hypothesis that DOXY alone or combined with Lithium (Li) could reverse AMPH-induced mania-like behavioral alterations in mice by the modulation of monoamine levels in brain areas related to mood regulation, as well as cytoprotective and antioxidant effects in hippocampal neurons.
Methods: Male Swiss mice received AMPH or saline intraperitoneal (IP) injections for 14 days. Between days 8-14, mice receive further IP doses of DOXY, Li, or their combination. For in vitro studies, we exposed hippocampal neurons to DOXY in the presence or absence of AMPH. Results: DOXY alone or combined with Li reversed AMPH-induced risk-taking behavior and hyperlocomotion. DOXY also reversed AMPH-induced hippocampal and striatal hyperdopaminergia. In AMPH-exposed hippocampal neurons, DOXY alone and combined with Li presented cytoprotective and antioxidant effects, while DOXY+Li also increased the expression of phospho-Ser133-CREB. Conclusion: our results add novel evidence for DOXY’s ability the reversal of mania-like features while revealing that antidopaminergic activity in some brain areas, such as the hippocampus and striatum, as well as hippocampal cytoprotective effects may account for this drug’s antimanic action. This study provides additional rationale for designing clinical trials investigating its potential as a mood stabilizer agent.
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