Chronic unpredictable mild stress decreases BDNF and NGF levels and Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant effect of chrysin.

Our working hypothesis is that brain neurotrophins and brain Na(+),K(+)-ATPase may be strongly associated with the occurrence of depression in animals subjected to chronic unpredictable mild stress (CUMS). Still, we believe that chrysin, a natural and bioactive flavonoid found in honey and some plants, can provide satisfactory effects on antidepressant therapy. Thus, we aimed to evaluate the effect of CUMS on brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF) levels as well as the Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of female mice. We also aimed to examine the effect of a 28-day oral treatment with chrysin (5 or 20mg/kg) in female mice subjected to CUMS, comparing to the effect of fluoxetine. Results showed that CUMS applied for 28days induced a decrease in BDNF and NGF levels as well as in the Na(+),K(+)-ATPase activity. CUMS also promoted a depressive status in the swimming forced test (FST), in the sucrose preference test, and in corticosterone levels. Chrysin (20mg/kg) and fluoxetine also occasioned the up-regulation of BDNF and NGF levels in non-stressed mice and in mice subjected to CUMS. CUMS decreased non-protein thiol (NPSH) levels and increased reactive oxygen species (ROS) levels. In response to these changes, the glutathione reductase (GR), glutathione peroxidase (GPx) and catalase (CAT) activities were increased in mice exposed to CUMS. Chrysin and fluoxetine treatments protected against all these alterations, suggesting the involvement of the antioxidant function in the antidepressant effect of chrysin and fluoxetine. In conclusion, CUMS decreased BDNF and NGF levels as well as the Na(+),K(+)-ATPase activity in mice. Chrysin presented antidepressant effect in mice on behavioral, neurotrophic and biochemistry parameters equivalent to fluoxetine. Furthermore, we suggest that the up-regulation of BDNF and NGF levels is a mechanism possibly involved in the antidepressant effect of chrysin in mice.

Neuroprotective effects of swimming training in a mouse model of Parkinson's disease induced by 6-hydroxydopamine.

Parkinson's disease (PD) is characterized by progressive dopamine (DA) depletion in the striatum. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegeneration diseases. This study was designed to investigate the potential neuroprotective effect of swimming training (ST) in a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) in mice. The present study demonstrated that a 4-week ST was effective in attenuating the following impairments resulting from 6-OHDA exposure: (i) depressive-like behavior in the tail suspension test; (ii) increase in the number of falls in the rotarod test; (iii) impairment on long-term memory in the object recognition test; (iv) increase of the reactive species and interleukin 1-beta (IL-1ß) levels; (v) inhibition of the glutathione peroxidase (GPx) activity; (vi) rise of the glutathione reductase (GR) and glutathione S-transferase (GST) activities and vii) decrease of DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. The mechanisms involved in this study are the modulation of GPx, GR and GST activities as well as IL-1ß level in a PD model induced by 6-OHDA, protecting against the decrease of DA, DOPAC and HVA levels in the striatum of mice. These findings reinforce that one of the effects induced by exercise on neurodegenerative disease, such as PD, is due to antioxidant and anti-inflammatory properties. We suggest that exercise attenuates cognitive and motor declines, depression, oxidative stress, and neuroinflammation induced by 6-OHDA supporting the hypothesis that exercise can be used as a non-pharmacological tool to reduce the symptoms of PD.

Involvement of oxidative stress in subacute toxicity induced by fumonisin B1 in broiler chicks.

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium spp. It has been reported to be a potential cause of liver cancer in rats and esophageal cancer in humans. The underlying mechanisms of FB1 toxicity are thought to be related to the inhibition of ceramide synthase, causing an accumulation of sphingosine (SO) and sphinganine (SA), which in turn may cause tissue functional impairment and the development of oxidative stress. Therefore, in this study, we investigate the effects of an FB1-contaminated diet on markers of oxidative stress in chick liver. A total of 24 male broiler chicks (Cobb 500) were fed a standard control diet or a diet contaminated with FB1 (100mg/kg) for 21 days, starting on postnatal day one. The feed and animals were weighed on days 0, 7, 14 and 21 to estimate the feed conversion ratio, and at 21 days, the liver weight and liver relative weight were determined. At the end of the experiment, samples of blood and liver were collected. The blood was used to quantify the SA/SO ratio, and the liver was used to determine the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST); ascorbic acid levels (VitC), non-protein thiol (NPSH) levels and TBARS content were also determined. The FB1 diet increased the liver weight, liver relative weight, feed conversion and SA/SO ratio. Furthermore, hepatic TBARS levels, Vit C content and CAT activity were also increased. Conversely, the activities of SOD, GST and NPSH levels, in the liver were not altered by the mycotoxin-contaminated diet. In summary, we showed that subacute exposure of broiler chicks to FB1 induced liver oxidative stress concomitantly with SA/SO accumulation.