Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites produced in the degradation of tryptophan and have important neurological activities. KYNA/QUIN ratio changes are known to be associated with central nervous system disorders, such Alzheimer, Parkinson, and Huntington diseases. In the present study, we investigate the ability of KYNA in prevent the first events preceding QUIN-induced neurodegeneration in striatal slices of rat. We evaluated the protective effect of KYNA on oxidative status (reactive oxygen species production, antioxidant enzymes activities, lipid peroxidation, nitrite levels, protein and DNA damage, and iNOS immunocontent), mitochondrial function (mitochondrial mass, membrane potential, and respiratory chain enzymes), and Na,K-ATPase in striatal slices of rats treated with QUIN. Since QUIN alters the levels of Nrf2, we evaluated the influence of KYNA protection on this parameter. Striatal slices from 30-day-old Wistar rats were preincubated with KYNA (100 μM) for 15 min, followed by incubation with 100-μM QUIN for 30 min. Results showed that KYNA prevented the increase of ROS production caused by QUIN and restored antioxidant enzyme activities and the protein and lipid damage, as well as the Nrf2 levels. KYNA also prevented the effects of QUIN on mitochondrial mass and mitochondrial membrane potential, as well as the decrease in the activities of complex II, SDH, and Na,K-ATPase. We suggest that KYNA prevents changes in Nrf2 levels, oxidative imbalance, and mitochondrial dysfunction caused by QUIN in striatal slices. This study elucidates some of the protective effects of KYNA against the damage caused by QUIN toxicity.

Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na, K-ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised+stressed). The animals were subjected to controlled exercise treadmill for 20min,three times a week, for two months prior to submission to the CVS (40days). Results show that CVS impaired performance in inhibitory avoidance at 24h and 7days after training session. CVS induced oxidative stress, increasing reactive species, lipoperoxidation and protein damage, and decreasing the activity of antioxidant enzymes. The activity of Na, K-ATPase was decreased, but the immunocontents and gene expression of catalytic subunits were not altered. The previous physical exercise was able to improve performance in inhibitory avoidance at 24h after training; additionally, exercise prevented oxidative damage, but was unable to reverse completely the changes observed on the enzymatic activities. Our findings suggest that physical exercise during the developmental period may protect against aversive memory impairment and brain oxidative damage caused by chronic stress exposure later in life.

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The aim of this study was to investigate the effect of ovariectomy (OVX), a surgical model of menopause, and/or vitamin D (VIT D) supplementation on oxidative status, DNA damage, and telomere length in hippocampus of rats at two ages. Ninety-day-old (adult) or 180-day-old (older) female Wistar rats were divided into four groups: SHAM, OVX, VIT D, and OVX + VIT D. Thirty days after OVX, rats were supplemented with VIT D (500 IU/kg) by gavage, for a period of 30 days. Results showed that OVX altered antioxidant enzymes, increasing the activities of catalase in adult rats and superoxide dismutase in older rats. VIT D per se increased the activities of catalase and superoxide dismutase in older rats, but not in adult rats. VIT D supplementation to OVX (OVX + VIT D) rats did not reverse the effect of OVX on catalase in adult rats, but it partially reversed the increase in superoxide dismutase activity in older rats. OVX increased DNA damage in hippocampus of adult and older rats. VIT D per se reduced DNA damage, and when associated to OVX, it partially reversed this alteration. Additionally, OVX caused a telomere shortening in older rats, and VIT D was able to reverse such effect. Taken together, these results demonstrate that surgical menopause in rats causes hippocampal biochemical changes and VIT D appears, at least in part, to act in a beneficial way.

The aim of this study was to verify the effects of ovariectomy (OVX) and/or vitamin D supplementation (VIT D) on inflammatory and cholinergic parameters in hippocampus, as well as on serum estradiol and VIT D levels of rats. Ninety-day-old female Wistar rats were randomly divided into four groups: SHAM, OVX, VIT D or OVX + VIT D. Thirty days after OVX, VIT D (500 IU/kg/day) was supplemented by gavage, for 30 days. Approximately 12 h after the last VIT D administration, rats were euthanized and hippocampus and serum were obtained for further analyses. Results showed that OVX rats presented a decrease in estradiol levels when compared to control (SHAM). There was an increase in VIT D levels in the groups submitted to VIT D supplementation. OVX increased the immunocontent of nuclear p-NF-κB/p65, TNF-α and IL-6 levels. VIT D partially reversed the increase in p-NF-κB/p65 immunocontent and IL-6 levels. Regarding cholinergic system, OVX caused an increase in acetylcholinesterase activity without changing acetylcholinesterase and choline acetyltransferase immunocontents. VIT D did not reverse the increase in acetylcholinesterase activity caused by OVX. These results demonstrate that OVX alters inflammatory and cholinergic parameters and that VIT D supplementation, at the dose used, partially reversed the increase in immunocontent of p-NF-Kb/p65 and IL-6 levels, but it was not able to reverse other parameters studied. Our findings may help in the understanding of the brain changes that occurs in post menopause period and open perspectives for futures research involving VIT D therapies.