Sulfite accumulates in tissues of patients affected by sulfite oxidase (SO) deficiency, a neurometabolic disease characterized by seizures and progressive encephalopathy, often resulting in early death. We investigated the effects of sulfite on mitochondrial function, antioxidant system, glial reactivity and neuronal damage in rat striatum, as well as the potential protective effects of bezafibrate on sulfite-induced toxicity. Thirty-day-old rats were intrastriatally administered with sulfite (2μmol) or NaCl (2μmol; control) and euthanized 30min after injection for evaluation of biochemical parameters and western blotting, or 7days after injection for analysis of glial reactivity and neuronal damage. Treatment with bezafibrate (30 or 100mg/kg/day) was performed by gavage during 7days before (pre-treatment) or after sulfite administration. Sulfite decreased creatine kinase and citrate synthase activities, mitochondrial mass, and PGC-1α nuclear content whereas bezafibrate pre-treatment prevented these alterations. Sulfite also diminished cytochrome c oxidase (COX) IV-1 content, glutathione levels and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH). On the other hand, catalase activity was increased by sulfite. Bezafibrate pre-treatment prevented the reduction of GPx, GR, GST and G6PDH activities. Finally, sulfite induced glial reactivity and neuronal damage, which were prevented by bezafibrate when administered before or after sulfite administration. Our findings provide strong evidence that sulfite induces neurotoxicity that leads to glial reactivity and neuronal damage. Since bezafibrate exerts neuroprotective effects against sulfite toxicity, it may be an attractive agent for the development of novel therapeutic strategies for SO-deficient patients.

Alzheimer's disease (AD) is the main aging-associated neurodegenerative disorder and is characterized by mitochondrial dysfunction, oxidative stress, synaptic failure, and cognitive decline. It has been a challenge to find disease course-modifying treatments. However, several studies demonstrated that regular physical activity and exercise are capable of promoting brain health by improving the cognitive function. Maternal lifestyle, including regular exercise during pregnancy, has also been shown to influence fetal development and disease susceptibility in adulthood through fetal metabolism programming. Here, we investigated the potential neuroprotective role of regular maternal swimming, before and during pregnancy, against amyloid-β neurotoxicity in the adult offspring. Behavioral and neurochemical analyses were performed 14 days after male offspring received a single, bilateral, intracerebroventricular (icv) injection of amyloid-β oligomers (AβOs). AβOs-injected rats of the sedentary maternal group exhibited learning and memory deficits, along with reduced synaptophysin, brain-derived neurotrophic factor (BDNF) levels, and alterations of mitochondrial function. Strikingly, the offspring of the sedentary maternal group had AβOs-induced behavioral alterations that were prevented by maternal exercise. This effect was accompanied by preventing the alteration of synaptophysin levels in the offspring of exercised dams. Additionally, offspring of the maternal exercise group exhibited an augmentation of functional mitochondria, as indicated by increases in mitochondrial mass and membrane potential, α-ketoglutarate dehydrogenase, and cytochrome c oxidase enzymes activities. Moreover, maternal exercise during pregnancy induced long-lasting modulation of fusion and fission proteins, Mfn1 and Drp1, respectively. Overall, our data demonstrates a potential protective effect of exercise during pregnancy against AβOs-induced neurotoxicity in the adult offspring brain, by mitigating the neurodegenerative process triggered by Alzheimer-associated AβOs through programming the brain metabolism.

No abstract

Our results reinforce the benefits of aerobic exercise, which include positive modulation of antioxidant homeostasis in the hippocampi. The effects of exercise are not permanent; rather, an exercise regimen must be continued in order to maintain the neurometabolic adaptations.

Prenatal and early postnatal environments can permanently influence health throughout life. Early overnutrition increases the risk to develop chronic diseases. Conversely, the intake of flavonoids and exercise practice during pregnancy seem to promote long-term benefits to offspring. We hypothesized that benefic interventions during pregnancy could protect against possible postnatal neurochemical alterations caused by overnutrition induced by reduced litter size. Female Wistar rats were divided into four groups: (1) sedentary + vehicle, (2) sedentary + naringenin, (3) swimming exercise + vehicle, and (4) swimming exercise + naringenin. One day after birth, the litter was culled to 8 pups (control) or 3 pups (overfed) per dam, yielding control and overfed subgroups for each maternal group. Serum of 21-days-old pups was collected, also the cerebellum, hippocampus, and hypothalamus were dissected. Litter size reduction increased fat mass and enhanced body weight. Maternal interventions, when isolated, caused reduced glucose serum levels in offspring nurtured in control litters. In the cerebellum, reducing the litter size decreased the activity of thioredoxin reductase, which was prevented by maternal supplementation with naringenin. Hippocampus and hypothalamus have shown altered antioxidant enzymes activities in response to litter size reduction. Interestingly, when maternal exercise and naringenin supplementation were allied, the effect disappeared, suggesting a concurrent effect of the two maternal interventions. In conclusion, exercise or naringenin supplementation during pregnancy can be important interventions for combating the increasing rates of overweight during the infancy and its related neurochemical changes, especially when applied isolated.