Developmental programming: intrauterine caloric restriction promotes upregulation of mitochondrial sirtuin with mild effects on oxidative parameters in the ovaries and testes of offspring.

According to the developmental origins of health and disease (DOHaD) hypothesis, changes in the maternal environment are known to reprogram the metabolic response of offspring. Known for its redox modulation, caloric restriction extends the lifespan of some species, which contributes to diminished cellular damage. Little is known about the effects of gestational caloric restriction, in terms of antioxidant parameters and molecular mechanisms of action, on the reproductive organs of offspring. This study assessed the effects of moderate (20%) caloric restriction on redox status parameters, molecular expression of sirtuin (SIRT) 1 and SIRT3 and histopathological markers in the ovaries and testes of adult rats that were subjected to gestational caloric restriction. Although enzyme activity was increased, ovaries from female pups contained high levels of oxidants, whereas testes from male pups had decreased antioxidant enzyme defences, as evidenced by diminished glyoxalase I activity and reduced glutathione content. Expression of SIRT3, a deacetylase enzyme related to cellular bioenergetics, was increased in both ovaries and testes. Previous studies have suggested that, in ovaries, diminished antioxidant metabolism can lead to premature ovarian failure. Unfortunately, there is little information regarding the redox profile in the testis. This study is the first to assess the redox network in both ovaries and testes, suggesting that, although intrauterine caloric restriction improves molecular mechanisms, it has a negative effect on the antioxidant network and redox status of reproductive organs of young adult rats.

Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression.

Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering with several neuroprogressive factors, and has been suggested to reverse neuropathological patterns seen in depression. These insights come at a time of great need for novel approaches, as prevalence is rising and current treatment options remain inadequate for a large number of people. The rapidly growing literature on ketamine's antidepressant potential has yielded multiple proposed mechanisms of action, many of which have implications for recently elucidated aspects of depressive pathology. This review aims to provide the reader with an understanding of neuroprogressive aspects of depressive pathology and how ketamine is suggested to act on it. Literature was identified through PubMed and Google Scholar, and the reference lists of retrieved articles. When reviewing the evidence of depressive pathology, a picture emerges of four elements interacting with each other to facilitate progressive worsening, namely stress, inflammation, neurotoxicity and neurodegeneration. Ketamine acts on all of these levels of pathology, with rapid and potent reductions of depressive symptoms. Converging evidence suggests that ketamine works to increase stress resilience and reverse stress-induced dysfunction, modulate systemic inflammation and neuroinflammation, attenuate neurotoxic processes and glial dysfunction, and facilitate synaptogenesis rather than neurodegeneration. Still, much remains to be revealed about ketamine's antidepressant mechanisms of action, and research is lacking on the durability of effect. The findings discussed herein calls for more longitudinal approaches when determining efficacy and its relation to neuroprogressive factors, and could provide relevant considerations for clinical implementation.

Maternal exercise during pregnancy modulates mitochondrial function and redox status in a sex-dependent way in adult offspring's skeletal muscle.

Maternal exercise has shown beneficial effects on mother and child. Literature confirm progeny's cognition improvement, and upregulation in neurotrophins, antioxidant network, and DNA repair system. Considering that there is a lack of information demonstrating the impact of maternal exercise on offspring's skeletal muscle, we aimed to investigate the mitochondrial and redox effects elicited by maternal swimming. Adult female Wistar rats were divided into three groups: control sedentary, free swimming, and swimming with overload (2% of the body weight). Exercised groups were submitted weekly to five swimming sessions (30 min/day), starting 1 week prior to the mating and lasting to the delivery. Gastrocnemius and soleus muscle from 60-day-old offspring were analyzed. Our results clearly showed a sex-dependent effect. Male soleus showed increased mitochondrial functionality in the overload group. Female muscle from the overload group adapted deeply. Considering the redox status, the female offspring delivered to overload exercised dams presented reduced oxidants levels and protein damage, allied to downregulated antioxidant defenses. We also observed an increase in the mitochondrial function in the gastrocnemius muscle of the female offspring born from overload exercised dams. Soleus from female delivered to the overload exercise group presented reduced mitochondrial activity, as well as reduced reactive species, protein carbonyls, and antioxidant network, when compared to the male. In conclusion, maternal exercise altered the redox status and mitochondrial function in the offspring's skeletal muscle in a sex-dependent way. The clinical implication was not investigated; however, the sexual dimorphism in response to maternal exercise might impact exercise resilience in adulthood.

Effect of Maternal Exercise on Diet-induced Redox Imbalance in Hippocampus of Adult Offspring.

Physical exercise practice has been increasingly recommended in the prevention and treatment of chronic diseases, causing a positive effect from body weight/fat loss to improved cognitive function. Maternal exercise seems to induce the same positive lifelong adaptations to the offspring. We hypothesized that maternal exercise can prevent redox imbalance in adult offspring's hippocampus exposed to a high-fat diet (HFD). Female Wistar rats were divided into three groups before and during pregnancy: (1) sedentary, (2) swimming exercise, and (3) swimming exercise with overload. On 60 days of age, the male pups were divided into standard diet or HFD for one month, yielding normal and HFD subgroups for each maternal condition. Maternal interventions did not alter gestational parameters, birth outcomes, and offspring weight gain from weaning to 90 days of age. The HFD consumption increased body fat, which was not prevented by maternal exercise. Serum glucose levels were increased by HFD, an effect that was prevented by unload maternal exercise. In the hippocampus, both maternal exercise intensities could increase antioxidant defense. Hippocampal redox homeostasis was impaired by HFD, causing increased superoxide levels, which was prevented by exercise without load, while overload caused only a reduction of the effect. In summary, the practice of swimming exercise without overload during pregnancy seems to be more beneficial when evaluated in animal model, preventing HFD induced redox imbalance and increasing antioxidant defense while overload swimming exercise during pregnancy demonstrated a negative effect on offspring submitted to HFD consumption.

Polyols accumulated in ribose-5-phosphate isomerase deficiency increase mitochondrial superoxide production and improve antioxidant defenses in rats' prefrontal cortex.

The ribose-5-phosphate isomerase deficiency is an inherited condition, which results in cerebral d-arabitol and ribitol accumulation. Patients present leukoencephalopathy, mental retardation, and psychomotor impairment. Considering that the pathophysiology of this disorder is still unclear, and literature are sparse and contradictory, reporting pro and antioxidant activities of polyols, the main objective of this study was to investigate some parameters of oxidative homeostasis of prefrontal cortex of rats incubated with d-arabitol and ribitol. We found evidences that ribitol promoted an increase in antioxidant enzymes activity (superoxide dismutase, catalase, and glutathione peroxidase), probably secondary to enhanced production of superoxide radical, measured by flow cytometry. Oxidation of proteins and lipids was not induced by polyols. Our data allow us to conclude that, at least in our methodological conditions, arabitol and ribitol probably have a secondary effect on the pathophysiology of ribose-5-phosphate isomerase deficiency.