The present study investigated mitochondrial adaptations and oxidative damage after 4 and 8 weeks of running training in skeletal muscle of mice. Twenty-one male mice (CF1, 30-35 g) were distributed into the following groups (n = 7): untrained (UT); trained-4 weeks (T4); trained-8 weeks (T8). Forty-eight hours after the last training session the animals were killed by decapitation and quadriceps (red portion) were removed and stored at -70 degrees C. Succinate dehydrogenase (SDH), complexes I, II, II-III and IV, lipoperoxidation (TBARS), protein carbonyls (PC) and total thiol content were measured. Results show that endurance training (8-wk) increases the SDH activity and complexes (I, II, III, IV), decreases oxidative damage (TBARS, CP) and increases total thiol content in skeletal muscle when compared to untrained animals. In conclusion, eight weeks of running training are necessary for increases in mitochondrial respiratory chain enzyme activities to occur, in association with decreased oxidative damage.

Summary:Purpose: N-methyl D-aspartate (NMDA) preconditioning has been used to prevent cellular death induced by glutamate or NMDA in cultured neurons. Quinolinic acid (QA)-induced seizures are used to average NMDA receptors-evoked neurotoxicity in animal models. The purpose of this study was to investigate the potential neuroprotective effects of NMDA preconditioning against QA-induced seizures and hippocampal damage in vivo.Methods: Mice were pretreated with nonconvulsant doses of NMDA for different times before i.c.v. QA infusion and observed for the occurrence of seizures. Hippocampal slices from mice were assayed to measure cellular viability.Results: NMDA preconditioning presented 53% protection against QA-induced seizures, as well as QA-induced cellular death in the hippocampus. The NMDA receptor antagonist, MK-801, prevented the protection evoked by NMDA preconditioning. The adenosine A 1 receptor antagonist, CPT, prevented the protection evoked by NMDA preconditioning against QA-induced seizures, but not against QA-induced hippocampal cellular damage. The adenosine A 1 receptor agonist, CPA, did not mimic the NMDA preconditioning-evoked protective effects.Conclusions: These results suggest that in vivo preconditioning with subtoxic doses of NMDA protected mice against seizures and cellular hippocampal death elicited by QA, probably through mechanisms involving NMDA receptors operating with adenosine A 1 receptors.

Statins are cholesterol-lowering agents due to the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Recent studies have shown statins possess pleiotropic effects, which appear to be independent from its cholesterol-lowering action. In this study, we investigated whether atorvastatin would have protective effects against hippocampal cell death promoted by quinolinic acid (QA)-induced seizures in mice. Mice were pretreated with Atorvastatin (1 or 10 mg/kg) or vehicle (saline, 0.9%), orally, once a day for 7 days before the intracerebroventricular (i.c.v.) QA infusion (36.8 nmol/site). Atorvastatin treatment with 1 mg/kg/day did not significantly prevent QA-induced seizures (13.34%). However, administration of atorvastatin 10 mg/kg/day prevented the clonic and/or tonic seizures induced by QA in 29.41% of the mice. Additionally, administration of atorvastatin 10 mg/kg/day significantly prevented QA-induced cell death in the hippocampus. Atorvastatin treatment promoted an increased Akt phosphorylation, which was sustained after QA infusion in both convulsed and non-convulsed mice. Moreover, atorvastatin pretreatment prevented the reduction in glutamate uptake into hippocampal slices induced by QA i.c.v. infusion. These results show that atorvastatin attenuated QA-induced hippocampal cellular death involving the Akt pathway and glutamate transport modulation. Therefore, atorvastatin treatment might be a useful strategy in the prevention of brain injury caused by the exacerbation of glutamatergic toxicity in neurological diseases such as epilepsy.

No abstract

Clinical and pre-clinical findings point to the critical role of ovarian hormones in modulating anxiety and depressive symptoms in female. However, few studies investigated the effects of long-term ovarian hormones withdrawal on animal behavior. The current study evaluated the behavioral effects of long-term ovariectomy (performed at 3 months of life) in adult (6 months old) and aged (18 months old) rats subjected to the elevated plus-maze and forced swimming tests. A substantial reduction in the time spent in open arms in adult and aged ovariectomized rats was observed compared to intact animal from the same age. A significant increase in the immobility time was observed in aged rats, ovariectomized or not, compared to adult rats. It should be noted that no alterations in the spontaneous locomotion were detected among groups. In addition, a reduction in serum concentrations of 17beta-estradiol was observed in adult ovariectomized and aged sham and ovariectomized rats compared to adult intact animals. Taken together, these findings suggest that anxiety-related behaviors were affected by ovariectomy, but not aging. However, the depressive-like behavior observed in aged rats seems to be much more influenced by senescence than ovarian hormones withdrawal. The presented results are discussed considering the effects of gradual and abrupt reduction of ovarian steroids concentrations, and the influence of aging on behavior of female rats.

No abstract

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

Exercise training has demonstrated cardioprotection effects. However, the exact mechanism behind this effect is not is clear. The present study evaluated the effects of 12 weeks of previous treadmill training on the levels of oxidative damage, antioxidant enzyme activity and injury in the myocardium of rats submitted to infarction induced by isoproterenol (ISO). Isoproterenol treatment (80 mg/kg given over 2 days in two equal doses) caused arrhythmias and 60% mortality within 24 h of the last injection in the control group (C + ISO) group when compared with the saline control group (saline). Creatine Kinase--MB levels were markedly increased in hearts from ISO-treated animals in the C + ISO group. Twelve weeks of treadmill training reduced superoxide production, lipid peroxidation levels and protein carbonylation in these animals, as well as increasing the activities and expressions of SOD and CAT. Previous training also reduced CK-MB levels and numbers of deaths by 40%, preventing the deleterious effects of ISO. Based on the data obtained in this study, it is suggested that 12-week treadmill training increases antioxidant enzymes, decreases oxidative damage and reduces the degree of infarction induced by ISO in the hearts of male rats.