Olive oil-rich diet during pregnancy/lactation attenuated the early life stress effects on depressive-like behavior and altered energy metabolism in the dorsal hippocampus in a sex-specific manner.

METHODS: and results: Pregnant Wistar rats received diets enriched in soybean oil (SO) or OO during gestation/lactation. At birth, litters were subdivided into MS or intact groups. After weaning, the pups received standard chow until adulthood, when they were subjected to behavioral tasks. At PND90 biochemical analyses were performed. Maternal OO-enriched diet prevented MS-induced higher weight gain, and decreased MS-induced anhedonic behavior. Increased latency to immobility and shorter immobility time were observed in the maternal OO-enrich diet groups. Maternal OO-enrich diet groups also presented reduced reactive oxygen species and increased activity of antioxidant enzymes. In addition, this diet showed sex-specific effects, by decreasing mitochondrial mass and potential, reducing AMPK activation, and increasing synaptophysin and PSD-95 immunocontent in the DH of male rats. Early stress, on the other hand, decreased production of free radicals and decreased levels of SIRT1 in the DH of male rats. In females, OO prevented the anhedonic behavior induced by MS. CONCLUSIONS: Maternal OO-enrich diet attenuated MS-induced depressive behavior in both sexes. In addition, it affected energy metabolism in the DH of male rats, favored synaptic plasticity, and contributed to reducing pathophysiological conditions.

Maternal polyphenol intake impairs cerebellar redox homeostasis in newborn rats.

INTRODUCTION: Polyphenols are compounds found in plants that have been extensively studied due to the health benefits of its consumption in adulthood. Meanwhile, recent evidence suggests that polyphenol consumption during pregnancy may not be safe for the fetus. OBJECTIVE: The goal of this study was to evaluate the effect of naringenin supplementation during pregnancy on brain redox homeostasis and mitochondrial activity of the newborn rat. METHODS: Adult female Wistar rats were divided into two groups: (1) vehicle (1 mL/Kg p.o.) or (2) naringenin (50 mg/Kg p.o.). Naringenin was administered once a day during pregnancy. The offspring were euthanized on postnatal day 7, as well the dams, and brain regions were dissected. RESULTS: The offspring cerebellum was the most affected region, presenting increased activity of the mitochondrial electron transport system, allied to increased reactive species levels, lipid peroxidation, and glutathione concentration. The nitric oxide levels suffered structure-dependent alteration, with decreased levels in the pups' cerebellum and increased in the hippocampus. The offspring parietal cortex was not affected, as well as the parameters evaluated in the dams' brains. CONCLUSION: Maternal consumption of naringenin alters offspring cerebellar redox homeostasis, which could be related to adverse effects on the motor and cognitive development in the descendants.

Influence of tropical, subtropical, and temperate climate conditions on seminal redox status and sperm quality parameters in breeding bulls.

This study evaluated the effect of climate change on andrological parameters of beef bulls raised under tropical, subtropical, and temperate conditions. Bull ejaculates were collected to evaluate seminal quality parameters, sperm membrane integrity, and redox status (SOD; GPx; GSH; GRx; CARB; DCF; and SOD/GPx ratio). Bulls located in the temperate region showed a higher sperm motility rate and percentage of viable sperm (P < 0.05). When evaluating regions independently, we observed a lower GPx activity from animals in the tropical region (P < 0.05). In contrast, we found that SOD and GRx activities, GSH content, and CARB oxidative levels were higher in the tropical region, while oxidation values of DCF were lower (P < 0.05). Braford bulls showed higher CARB and DCF levels (1.23 ± 0.61 nmol/mg and 1453.60 ± 828.63 nmol/mg, respectively) compared to Hereford bulls (1.00 ± 0.43 nmol/mg and 1138.70 ± 423.24 nmol/mg, respectively) in the temperate region. However, Nellore bulls showed higher DCF levels (650.50 ± 401.53 nmol/mg) than Braford bulls (409.40 ± 286.97 nmol/mg). In addition, the SOD/GPx ratio was lower in Braford (12.44 ± 7.64 U/mg) compared to Nellore bulls in tropical conditions (87.25 ± 2.83 U/mg). A positive correlation was found in temperate conditions between DCF levels, SOD, and GRx activities (0.51, 0.58; P < 0.01, respectively), as well as in subtropical conditions between DCF levels and GRx activity (0.53; P < 0.01). A negative correlation between the temperature-humidity index and CARB content was found in subtropical and tropical regions (-0.44; P < 0.01). We concluded that Braford breeds showed lower seminal motility, DCF contents and SOD/GPx ratios compared to Nellore bulls in tropical climate conditions. Finally, in temperate environmental conditions, Braford bulls also showed lower seminal motility but higher levels of CARB and DCF contents compared to Hereford bulls. Therefore, the existence of climatic differences between the temperate and tropical regions evaluated affected Braford bulls' seminal motility and seminal redox homeostasis.

Gestational caloric restriction with micronutrients supplementation does not delay development and promotes feeding behavior benefits.

Introduction: Caloric restriction (CR) has been proven to promote a series of health benefits from yeast to primates. Nowadays, increasing rates of obesity certainly encourage researchers to evaluate CR effects and establish it as a therapeutic approach. Maternal obesity is also a concern, and studies in the developmental origins of health and disease (DOHaD) have shown the importance of interventions during pregnancy, especially those involving maternal nutrition. On the other hand, undernutrition during pregnancy leads to increased weight gain, disturbed feeding behavior and dysfunctional metabolism in adulthood.Methods: In this way, we utilized moderate CR (20% compared to control consumption) in pregnant Wistar rats as intervention, with malnutrition control by micronutrients supplementation. We assessed CR effects on offspring's developmental milestones, feeding behavior, exploratory behavior, and memory on adolescence (PND21) and adulthood (PND60).Results: We did not find alterations on litter size or birth weight, although CR pups were leaner at adult ages. Importantly, no delay in development was observed. Besides, female pups showed earlier suction reflex and male pups showed earlier response to the negative geotaxis. CR pups also showed less preference for palatable food (Froot Loops®) at adult age, which could be decisive on obesity tendency. Locomotor activity was increased by CR on PND60 and there was no effect on memory at all.Discussion: Our results on development and behavior demonstrate that gestational CR may be a helpful health strategy if malnutrition is well controlled, with potential clinical impact.

Tricarboxylic acid cycle dehydrogenases inhibition by naringenin: experimental and molecular modelling evidence.

The study of polyphenols' effects on health has been gaining attention lately. In addition to reacting with important enzymes, altering the cell metabolism, these substances can present either positive or negative metabolic alterations depending on their consumption levels. Naringenin, a citrus flavonoid, already presents diverse metabolic effects. The objective of this work was to evaluate the effect of maternal naringenin supplementation during pregnancy on the tricarboxylic acid cycle activity in offspring's cerebellum. Adult female Wistar rats were divided into two groups: (1) vehicle (1 ml/kg by oral administration (p.o.)) or (2) naringenin (50 mg/kg p.o.). The offspring were euthanised at 7th day of life, and the cerebellum was dissected to analyse citrate synthase, isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH) and malate dehydrogenase (MDH) activities. Molecular docking used SwissDock web server and FORECASTER Suite, and the proposed binding pose image was created on UCSF Chimera. Data were analysed by Student's t test. Naringenin supplementation during pregnancy significantly inhibited IDH, α-KGDH and MDH activities in offspring's cerebellum. A similar reduction was observed in vitro, using purified α-KGDH and MDH, subjected to pre-incubation with naringenin. Docking simulations demonstrated that naringenin possibly interacts with dehydrogenases in the substrate and cofactor binding sites, inhibiting their function. Naringenin administration during pregnancy may affect cerebellar development and must be evaluated with caution by pregnant women and their physicians.

Comparison of photobiomodulation using either an intraoral or an extraoral laser on oral mucositis induced by chemotherapy in rats.

PURPOSE: The aim of the present study was to compare the effect of intraoral (IO) and extraoral (EO) diode laser irradiation on oral mucositis (OM) induced by 5-fluorouracil (5-FU) in rats. METHODS: Animals (n = 78) were divided into the following groups: negative control (NC), positive control (PC), IO 6 J/cm2, EO with 6 J/cm2 (EO 6 J/cm2), and 12 J/cm2 (EO 12 J/cm2). OM was induced with an intraperitoneal injection of 5-FU and scarification of the buccal mucosa. Over the following 14 days, animals received photobiomodulation (PBM) daily. Clinical and histological evaluation was done by scores at days 8, 10, and 14. The redox state was evaluated by reactive species levels, antioxidant network, and immunohistochemistry analysis. RESULTS: Clinically, on day 8, PBM groups showed lower scores of OM with EO 6 J/cm2 presenting a significantly lower degree compared to PC (p < 0.05). On days 10 and 14, all PBM groups exhibited improvement of OM compared to PC (p < 0.01). On day 8, all PBM groups exhibited an accelerated healing process compared to PC (p < 0.01) and reduction of reactive species (p < 0.001). Also, all PBM groups demonstrated higher levels of antioxidant GPx compared to PC (p < 0.001). Analysis of nitrotyrosine revealed that on day 14, this protein damage marker was significantly reduced in the EO 6 J/cm2 group (p > 0.05). CONCLUSIONS: An EO diode laser protocol promoted positive effects in the clinical, histopathological, and redox state in OM induced by 5-FU in rats. Among the EO protocols, EO 6 J/cm2 showed the most encouraging results.

Maternal high-salt diet alters redox state and mitochondrial function in newborn rat offspring's brain.

Excessive salt intake is a common feature of Western dietary patterns, and has been associated with important metabolic changes including cerebral redox state imbalance. Considering that little is known about the effect on progeny of excessive salt intake during pregnancy, the present study investigated the effect of a high-salt diet during pregnancy and lactation on mitochondrial parameters and the redox state of the brains of resulting offspring. Adult female Wistar rats were divided into two dietary groups (n 20 rats/group): control standard chow (0·675 % NaCl) or high-salt chow (7·2 % NaCl), received throughout pregnancy and for 7 d after delivery. On postnatal day 7, the pups were euthanised and their cerebellum, hypothalamus, hippocampus, prefrontal and parietal cortices were dissected. Maternal high-salt diet reduced cerebellar mitochondrial mass and membrane potential, promoted an increase in reactive oxygen species allied to superoxide dismutase activation and decreased offspring cerebellar nitric oxide levels. A significant increase in hypothalamic nitric oxide levels and mitochondrial superoxide in the hippocampus and prefrontal cortex was observed in the maternal high-salt group. Antioxidant enzymes were differentially modulated by oxidant increases in each brain area studied. Taken together, our results suggest that a maternal high-salt diet during pregnancy and lactation programmes the brain metabolism of offspring, favouring impaired mitochondrial function and promoting an oxidative environment; this highlights the adverse effect of high-salt intake in the health state of the offspring.

Higher susceptibility of cerebral cortex and striatum to sulfite neurotoxicity in sulfite oxidase-deficient rats.

Patients affected by sulfite oxidase (SO) deficiency present severe seizures early in infancy and progressive neurological damage, as well as tissue accumulation of sulfite, thiosulfate and S-sulfocysteine. Since the pathomechanisms involved in the neuropathology of SO deficiency are still poorly established, we evaluated the effects of sulfite on redox homeostasis and bioenergetics in cerebral cortex, striatum, cerebellum and hippocampus of rats with chemically induced SO deficiency. The deficiency was induced in 21-day-old rats by adding 200ppm of tungsten, a molybdenum competitor, in their drinking water for 9weeks. Sulfite (70mg/kg/day) was also administered through the drinking water from the third week of tungsten supplementation until the end of the treatment. Sulfite decreased reduced glutathione concentrations and the activities of glutathione reductase and glutathione S-transferase (GST) in cerebral cortex and of GST in cerebellum of SO-deficient rats. Moreover, sulfite increased the activities of complexes II and II-III in striatum and of complex II in hippocampus, but reduced the activity of complex IV in striatum of SO-deficient rats. Sulfite also decreased the mitochondrial membrane potential in cerebral cortex and striatum, whereas it had no effect on mitochondrial mass in any encephalic tissue evaluated. Finally, sulfite inhibited the activities of malate and glutamate dehydrogenase in cerebral cortex of SO-deficient rats. Taken together, our findings indicate that cerebral cortex and striatum are more vulnerable to sulfite-induced toxicity than cerebellum and hippocampus. It is presumed that these pathomechanisms may contribute to the pathophysiology of neurological damage found in patients affected by SO deficiency.

Bezafibrate prevents mitochondrial dysfunction, antioxidant system disturbance, glial reactivity and neuronal damage induced by sulfite administration in striatum of rats: Implications for a possible therapeutic strategy for sulfite oxidase deficiency.

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.

The effects of strength, aerobic, and concurrent exercise on skeletal muscle damage in rats.

INTRODUCTION: In this study we examined oxidative stress and skeletal muscle damage resulting from acute strength, aerobic, or concurrent exercise in rats. METHODS: The animals were divided into control (C), strength (SE), aerobic (AE), and combined (CE) exercise groups. They were euthanized at 3 different time-points (6, 24, and 48 h) after acute exercise. RESULTS: SE exercise rats had increased dichlorofluorescein oxidation at 6 h post-exercise and decreased superoxide dismutase activity at all time-points. Glutathione peroxidase activity and sulfhydryl levels were increased in the AE group at 48 h post-exercise. Serum lactate dehydrogenase activity was increased in the SE and CE groups at 24 h and in the AE group at 48 h. Echo intensity was elevated at 24 h for all groups. CONCLUSIONS: Forty-eight hours was sufficient for complete recovery from oxidative stress and muscle damage in the SE and CE groups, but not in the AE group.

Late pregnancy maternal naringin supplementation affects the mitochondria in the cerebellum of Wistar rat offspring via sirtuin 3 and AKT.

Dietary polyphenol consumption is associated with a wide range of neuroprotective effects by improving mitochondrial function and signaling. Consequently, the use of polyphenol supplementation has been investigated as an approach to prevent neurodevelopmental diseases during gestation; however, the data obtained are still very inconclusive, mostly because of the difficulty of choosing the correct doses and period of administration to properly prevent neurodegenerative diseases without undermining normal brain development. Thus, we aimed to evaluate the effect of naringin supplementation during the third week of gestation on mitochondrial health and signaling in the cerebellum of 21-day-old offspring. The offspring born to naringin-supplemented dams displayed higher mitochondrial mass, membrane potential, and superoxide content in the cerebellum without protein oxidative damage. Such alterations were associated with dynamin-related protein 1 (DRP1) and phosphorylated AKT (p-AKT) downregulation, whereas the sirtuin 3 (SIRT3) levels were strongly upregulated. Our findings suggest that high dietary polyphenol supplementation during gestation may reduce mitochondrial fission and affect mitochondrial dynamics even 3 weeks after delivery via SIRT3 and p-AKT. Although the offspring born to naringin dams did not present neurobehavioral defects, the mitochondrial alterations elicited by naringin may potentially interfere during neurodevelopment and need to be further investigated.

Influence of gestational exercise practice and litter size reduction on maternal care.

Mother-pup interactions are extremely important to offspring survival and growth. The goal of this study was to evaluate the influence of prenatal and neonatal interventions on maternal care, analyzing the effect of maternal exercise, as a healthy intervention, and also the litter size reduction, a model that has been widely used to study early overfeeding in rats. Female Wistar rats were divided into 1) sedentary, and 2) swimming exercise for four weeks, starting one week before mating (5 days/week, 30 min/session). One day after birth, the litter was culled to 8 pups (normal) or 3 pups (small) per dam, yielding control and overfed subgroups for each maternal group, respectively. From postnatal days 2-9 the litter was observed 5 periods a day, to evaluate maternal behavior. Litter reduction caused important alterations in maternal behavior, reducing the total time out of the nest and increasing the frequency of maternal care and lactation in several observation periods, justifying the increased pup's weight gain already demonstrated by this animal model. The practice of maternal exercise did not prevent, but cause the less intensive frequency of non-maternal behavior and lactation in arched-back position, induced by the reduction of litter size. These data demonstrated that small litter size altered maternal behavior, and gestational exercise does not influence significantly these changes.

Naringin Supplementation during Pregnancy Induces Sex and Region-Specific Alterations in the Offspring's Brain Redox Status.

Research has shown the beneficial effects of naringin supplementation to adult rodents, which can ameliorate oxidative stress in disease models. However, evidence has demonstrated that polyphenol supplementation induced detrimental effects when consumed during sensitive periods of development, such as pregnancy. Therefore, we investigated the effect of maternal naringin supplementation during pregnancy on the offspring's cerebral redox status. Pregnant Wistar rats were divided into control and naringin groups and supplemented from gestational day 15 to gestational day 21. On postnatal days 1, 7, and 21, offspring were euthanized, and the prefrontal cortex, hippocampus, striatum, and cerebellum dissected. On postnatal day 1, maternal naringin supplementation positively modulated the pups' brain redox status. On postnatal day 7, a pro-oxidative milieu was observed in the offspring's striatum and cerebellum in a sex-dependent manner, even though the prefrontal cortex and hippocampus were not negatively affected. Besides, the alterations observed on postnatal day 7 did not persist up to weaning. Our findings demonstrated that the effect induced by naringin supplementation in the brain redox status differed according to the period of development in which naringin was consumed since the beneficial effects usually found in the adult rodents became detrimental when the supplementation was applied during pregnancy.

Genistein attenuates amyloid-beta-induced cognitive impairment in rats by modulation of hippocampal synaptotoxicity and hyperphosphorylation of Tau.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aß) peptide, which induces synaptic dysfunction, alteration of intracellular signaling pathways, hyperphosphorylation of the Tau protein, and cognitive impairment. Genistein, one of the major isoflavones present in soy and soy products, has been shown to modulate some of the pathogenic events associated with the neurodegeneration process. However, its underlying mechanisms remain to be clarified. Therefore, the objectives of the present study were to evaluate the ability of genistein to protect against Aß1-42-induced cognitive impairment in rats and to elucidate some of the possible mechanisms involved in its neuroprotective effects in the hippocampus. Male Wistar rats received bilateral intracerebroventricular infusions of Aß1-42 (2 nmol) and genistein 10 mg/kg orally for 10 days. The Aß-infused animals showed significant impairment of memory, which was accompanied by the following neurochemical alterations in the hippocampus: decreased levels of the synaptic proteins synaptophysin and postsynaptic density protein 95 (PSD-95), hyperphosphorylation of Tau with increased activation of glycogen synthase kinase-3ß and c-Jun N-terminal kinase, and inactivation of ERK. Treatment with genistein improved Aß-induced cognitive impairment by attenuation of synaptotoxicity, hyperphosphorylation of Tau, and inactivation of ERK. Furthermore, treatment with this soy isoflavone did not cause systemic toxicity. These findings provide further evidence of the neuroprotective effect of genistein in an in vivo model of Aß toxicity and, importantly, extend the current knowledge concerning the mechanisms associated with the neuroprotective effects of this compound in the hippocampus.

Methylphenidate affects memory, brain-derived neurotrophic factor immunocontent and brain acetylcholinesterase activity in the rat.

Methylphenidate, a psychostimulant that affects both dopaminergic and noradrenergic systems, is one of the most frequently prescribed treatments for attention-deficit hyperactivity disorder. The present study investigated the effects of chronic administration of methylphenidate to juvenile rats on spatial memory, brain-derived neurotrophic factor immunocontent and acetylcholinesterase activity in hippocampus and prefrontal cortex. Rats received intraperitoneal injections of methylphenidate (2.0mg/kg) once a day, from the 15th to the 45th day of age or an equivalent volume of 0.9% saline solution (controls). Twenty-four hours after the last injection, animals were subjected to testing in the Morris water maze. After that, animals were sacrificed and hippocampus and prefrontal cortex were dissected out for determination of brain-derived neurotrophic factor immunocontent and acetylcholinesterase activity. Chronic administration of methylphenidate provoked cognitive impairments on spatial reference and working memory tasks. A reduction on brain-derived neurotrophic factor immunocontent and increased acetylcholinesterase activity in prefrontal cortex, but not in hippocampus, of rats treated with methylphenidate were also observed. These results suggest that the deficit in spatial memory may be associated to decreased brain-derived neurotrophic factor immunocontent and increased acetylcholinesterase in prefrontal cortex of juvenile rats subjected to methylphenidate administration.

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.

Early weaning alters redox status in the hippocampus and hypothalamus of rat pups.

Exposure to environmental factors can program the metabolism, conferring resistance or increasing the risk to chronic disease development in childhood and adulthood. In this sense, lactation is an important period in this window of development. Herein, we investigated the effect of early weaning on neurochemical and behavioral changes in offspring at weaning and adulthood. Female and male pups were divided into four groups: (1) Control weaning (weaning on the PND21, pups were kept with the biological mother); (2) Early Weaning Bromocriptine group (EWB) (pharmacological weaning on PND16); (3) Early Weaning Cross-Fostering group (EWCF) (pups housed with a foster mother on PND16 up to PND21); (4) Early Weaning Without Care group (EWWC) (weaning on PND16, maternal separation). Weight control of pups was recorded from postnatal Day 16 to 59. On the 21st day, part of the pups was euthanized and the hippocampus and hypothalamus were removed for biochemical evaluation. The remaining pups were submitted to behavioral tests on the 60th postnatal day. Early weaning reduced the pups' body weight, in a sex-dependent way. At 60 days of age, male pups of EWCF and EWWC groups have lower body weight compared to control male, and female body weight was lower than male pups. In relation to biochemical changes in the brain, weaning altered the levels of oxidants, increased the enzymatic activity of superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as induced lipid peroxidation. Weaning was also able to alter long-term memory and induce anxious behavior in pups. Our results demonstrate that the different types of early weaning changed the parameters of redox status in the hippocampus and hypothalamus of pups (21 days old), suggesting a prooxidative profile, in addition, to alter learning/memory and inducing an anxious behavior in male offspring (60 days old).

Protective effect of maternal exercise against amyloid-ß neurotoxicity in the male rat offspring's cerebellum.

The Developmental Origins of Health and Disease (DOHaD) states that intrauterine maternal environment influences postnatal life by programming offspring's metabolism. Intrauterine milieu induced by exercise during pregnancy promotes long-lasting benefits to the offspring's health and seems to offer some resistance against chronic diseases in adult life. Alzheimer's disease is a public health concern with limited treatment options. In the present study, we assessed the potential of maternal exercise during pregnancy in long-term programming of young adult male rat offspring's cerebellar metabolism in conferring neuroprotection against amyloid-ß (Aß) neurotoxicity. Female Wistar rats were submitted to a swimming protocol 1 week prior mating and throughout pregnancy (five sessions/a week lasting 30 min). Aß oligomers were infused bilaterally in the brain ventricles of 60-day-old male offspring. Fourteen days after surgery, we measured parameters related to redox state, mitochondrial function, and the immunocontent of proteins related to synaptic function. We found that maternal exercise during pregnancy attenuated several parameters in the offspring's male rat cerebellum, such as the reactive species rise, the increase of inducible nitric oxide synthase immunocontent and tau phosphorylation induced by Aß oligomers, increased mitochondrial fission indicated by dynamin-related protein 1 (DRP1), and protein oxidation identified by carbonylation. Strikingly, we find that maternal exercise promotes changes in the rat offspring's cerebellum that are still evident in young adult life. These favorable neurochemical changes in offspring's cerebellum induced by maternal exercise may contribute to a protective phenotype against Aß-induced neurotoxicity in young adult male rat offspring.

Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid.

We have previously demonstrated that acute hyperhomocysteinemia induces oxidative stress in rat brain. In the present study, we initially investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative damage, namely total radical-trapping antioxidant potential and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), as well as on DNA damage in parietal cortex and blood of rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of Hcy (0.3-0.6 micromol/g body weight), and/or folic acid (0.011 micromol/g body weight) from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, parietal cortex and total blood was collected. Results showed that chronic homocysteine administration increased DNA damage, evaluated by comet assay, and disrupted antioxidant defenses (enzymatic and non-enzymatic) in parietal cortex and blood/plasma. Folic acid concurrent administration prevented homocysteine effects, possibly by its antioxidant and DNA stability maintenance properties. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in disorders that accumulate homocysteine.

Na+,K+-ATPase activity in an animal model of mania.

We evaluated Na(+),K(+)-ATPase activity in hippocampus of rats submitted to an animal model of mania which included the use of lithium and valproate. In the acute treatment, amphetamine or saline was administered to rats for 14 days, between day 8 and 14, rats were treated with lithium, valproate or saline. In the maintenance treatment, rats were treated with lithium, valproate or saline, between day 8 and 14, amphetamine or saline were administered. Locomotor activity was assessed by open field test and Na(+),K(+)-ATPase activity was measured. Our results showed that mood stabilizers reversed and prevented amphetamine-induced behavioral effects. Moreover, amphetamine (acute treatment) increased Na(+),K(+)-ATPase activity, and administration of lithium or valproate reversed this effect. In the maintenance treatment, amphetamine increased Na(+),K(+)-ATPase activity in saline-pretreated rats. Amphetamine administration in lithium- or valproate-pretreated animals did not alter Na(+),K(+)-ATPase activity. The findings suggest that amphetamine-induced hyperactivity may be associated with an increase in Na(+),K(+)-ATPase.