The deleterious effects of maternal protein deprivation on the brainstem are minimized with moderate physical activity by offspring during early life.

Maternal protein malnutrition during developmental periods might impair the redox state and the brain's excitatory/inhibitory neural network, increasing central sympathetic tone. Conversely, moderate physical exercise at an early age reduces the risk of chronic diseases. Thus, we hypothesized that a moderate training protocol could reduce the harmful effects of a low-protein maternal diet on the brainstem of young male offspring. We used a rat model of maternal protein restriction during the gestational and lactation period followed by an offspring's continuous treadmill exercise. Pregnant rats were divided into two groups according to the protein content in the diet: normoprotein (NP), receiving 17% of casein, and low protein (LP), receiving 8% of casein until the end of lactation. At 30 days of age, the male offspring were further subdivided into sedentary (NP-Sed and LP-Sed) or exercised (NP-Ex and LP-Ex) groups. Treadmill exercise was performed as follows: 4 weeks, 5 days/week, 60 min/day at 50% of maximal running capacity. The trained animals performed a treadmill exercise at 50% of the maximal running capacity, 60 min/day, 5 days/week, for 4 weeks. Our results indicate that a low-protein diet promotes deficits in the antioxidant system and a likely mitochondrial uncoupling. On the other hand, physical exercise restores the redox balance, which leads to decreased oxidative stress caused by the diet. In addition, it also promotes benefits to GABAergic inhibitory signaling. We conclude that regular moderate physical exercise performed in youthhood protects the brainstem against changes induced by maternal protein restriction.

Effects of perinatal protein restriction on the oxidative balance in the hypothalamus of 60-day-old rats / Efeitos da restrição proteica perinatal sobre o balanço oxidativo no hipotálamo de ratos de 60 dias de idade

ABSTRACT Objective Evaluate the effects of maternal low-protein diet on the oxidative stress in the hypothalamus of 60-day-old rats. Methods Male Wistar rats were divided into two experimental groups according to the mother's diet during pregnancy and lactation; control group (NP:17% casein n=6) and a malnourished group (LP:8% casein n=6). At 60 days of life, the rats were sacrificed for the collection of the hypothalamus for further biochemical analysis. Results Our results showed an increase in oxidative stress in malnourished group, observed through an increase in carbonyl content (p=0.0357), a reduction in the activity of the glutathione-S-transferase enzyme (p=0.0257), and a reduction in the non-enzymatic antioxidant capacity evidenced by the decrease in the ratio reduced glutathione/oxidized glutathione (p=0.0406) and total thiol levels (p=0.0166). Conclusion A low-protein diet during pregnancy and lactation is closely associated with increased oxidative stress and reduced antioxidant capacity in the hypothalamus of sixty-day-old rats.

RESUMO Objetivo Avaliar os efeitos da restrição proteica materna sobre o estresse oxidativo no hipotálamo de ratos de 60 dias de idade. Métodos Ratos Wistar machos foram divididos em dois grupos experimentais de acordo com a dieta da mãe durante a gestação e lactação: grupo controle (NP: 17% caseína n=6) e grupo desnutrido (LP: 8% caseína n=6). Aos 60 dias de vida, os ratos foram sacrificados para coleta do hipotálamo para posterior análise bioquímica. Resultados Os resultados demonstraram aumento do estresse oxidativo no grupo desnutrido, observado através do aumento do conteúdo de cabonilas (p=0,0357) e redução da atividade da enzima glutationa-S-transferase (p=0,0257) e da capacidade antioxidante não enzimática, evidenciada pela queda da razão glutationa reduzida/glutationa oxidada (p=0,0406) e dos níveis de tióis totais (p=0,0166). Conclusão Uma dieta com baixo teor de proteínas durante a gestação e lactação está intimamente associada ao aumento do estresse oxidativo e à redução da capacidade antioxidante no hipotálamo de ratos de 60 dias de vida.

Effects of aerobic exercise training in oxidative metabolism and mitochondrial biogenesis markers on prefrontal cortex in obese mice.

BACKGROUND: To evaluate the effects of 8 weeks of Aerobic Physical Training (AET) on the mitochondrial biogenesis and oxidative balance in the Prefrontal Cortex (PFC) of leptin deficiency-induced obese mice (ob/ob mice). METHODS: Then, the mice were submitted to an 8-week protocol of aerobic physical training (AET) at moderate intensity (60% of the maximum running speed). In the oxidative stress, we analyzed Malonaldehyde (MDA) and Carbonyls, the enzymatic activity of Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione S Transferase (GST), non-enzymatic antioxidant system: reduced glutathione (GSH), and Total thiols. Additionally, we evaluated the gene expression of PGC-1α SIRT-1, and ATP5A related to mitochondrial biogenesis and function. RESULTS: In our study, we did not observe a significant difference in MDA (p = 0.2855), Carbonyl's (p = 0.2246), SOD (p = 0.1595), and CAT (p = 0.6882) activity. However, the activity of GST (p = 0.04), the levels of GSH (p = 0.001), and Thiols (p = 0.02) were increased after 8 weeks of AET. Additionally, there were high levels of PGC-1α (p = 0.01), SIRT-1 (p = 0.009), and ATP5A (p = 0.01) gene expression after AET in comparison with the sedentary group. CONCLUSIONS: AET for eight weeks can improve antioxidant defense and increase the expression of PGC-1α, SIRT-1, and ATP5A in PFC of ob/ob mice.

Undernutrition during development modulates endoplasmic reticulum stress genes in the hippocampus of juvenile rats: Involvement of oxidative stress.

To evaluate whether exercise training mitigates the deleterious effects of undernutrition during the developmental period in juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17 % or 8 % casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein non-trained (LS), Low-Protein Trained (LT), Normoprotein non-trained (NS), and Normoprotein Trained (NT). Trained rats performed aerobic exercise training (AET) for 4 weeks, 5 days a week, 1 h a day. 24 h from the last day of training, the animals were sacrificed. The tissues were removed to analyze indicators of mitochondrial metabolism, oxidative stress, and gene expression of GRP78, PERK, ATF6 ER stress markers, and BDNF. The results showed that undernutrition during development promotes deleterious effects on mitochondrial oxidative metabolism and induces reticulum stress in the hippocampus of juvenile rats. On the other hand, AET improves mitochondrial function and increases enzymatic and non-enzymatic antioxidant capacity, as well as declines ER stress. AET at moderate intensity for 4 weeks in male juvenile Wistar rats acts as a lifestyle intervention opposing the negative effects induced by a protein-restricted maternal diet.

Maternal safflower oil consumption improve reflex maturation, memory and reduces hippocampal oxidative stress in the offspring rats treated during pregnancy and lactation.

OBJECTIVE: Evaluate the influence of maternal consumption of safflower oil on reflex maturation, memory and offspring hippocampal oxidative stress. METHODOLOGY: Two groups were formed: control group (C), whose mothers received a standard diet, and Safflower group (SF), whose mothers received a normolipidic diet with safflower oil as lipid source. Treatment was given from the 14th day of gestation and throughout lactation. To evaluate newborn development, the reflex ontogeny indicators between the 1st and the 21st days of life were evaluated; to assess memory, from the 42nd day of life on these animals were examined on open field habituation and novel object recognition test. Following behavioral analysis, the animals were anesthetized and decapitated. Hippocampus was rapidly dissected. In the hippocampal tissues, we evaluated the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST) and reduced glutathione (GSH). RESULTS: SF offspring showed delayed maturation of reflexes and improvement of novel object recognition in short-term and long-term (p < 0.05). Safflower oil decreases lipid peroxidation evaluated by MDA levels (p < 0.001) and increases antioxidant defenses as shown by SOD, CAT, GST and GSH levels (p < 0.05). In our study, the composition of flavonoids present in the oil was not evaluated. Furthermore, in a future study, the effect of maternal consumption on female offspring should be verified. CONCLUSION: Maternal intake of safflower oil could: (1) change neonate reflex parameters, (2) promote improvement of cognitive development in adolescence (3) improve antioxidant enzymatic and non-enzymatic defenses in the hippocampus.

Overfeeding during development induces temporally-dependent changes in areas controlling food intake in the brains of male Wistar rats.

AIMS: We sought to evaluate the effects of overfeeding during lactation on the feeding behavior and expression of specific regulatory genes in brain areas associated with food intake in 22- and 60-day old male rats. METHODS: We evaluated body weight, food intake of standard and palatable diet, and mRNA expression of dopamine receptor D1 (DDR1), dopamine receptor (DDR2), melanocortin 4 receptor (MC4R), the µ-opioid receptor (MOR), neuropeptide Y (NPY), agouti-related protein (AGRP), proopiomelanocortin (POMC), cocaine-and amphetamine-regulated transcript (CART), serotonin (5-hydroxytryptamine; 5-HT) transporter (SERT), 5-hydroxytryptamine receptor 1B (5-HT1B), 5-hydroxytryptamine receptor 2C receptor (5-HT2C), Clock (CLOK), cryptochrome protein 1 (Cry1) and period circadian protein homolog 2 (Per2) in the striatum, hypothalamus and brainstem of male rats at post-natal days (PND) 22 and 60. KEY FINDINGS: Overfeeding resulted in significantly increased body weight through PND60, and a 2-fold increase in palatable food intake at PND22, but not at PND60. We observed significant increases in DDR1, DDR2, and MC4R gene expression in the striatum and brainstem and POMC/CART in the hypothalamus of the OF group at PND22 that were reversed by PND60. Hypothalamic levels of 5-HT1B, 5-HT2C and NPY/AGRP on the other hand were decreased at PND22 and increased at PND60 in OF animals. Clock genes were unaffected by OF at PND22, but were significantly elevated at PND60. SIGNIFICANCE: Overfeeding during early development of the rat brain results in obesity and altered feeding behavior in early adulthood. The altered behavior might be the consequence of the changes in food intake and reward gene expression.

Moderate offspring exercise offsets the harmful effects of maternal protein deprivation on mitochondrial function and oxidative balance by modulating sirtuins.

BACKGROUND AND AIMS: It has been demonstrated that maternal low protein during development induces mitochondrial dysfunction and oxidative stress in the heart. Moderate-intensity exercise in early life, conversely, increases the overall cardiac health. Thus, we hypothesize that moderate-intensity exercise performed during young age could ameliorate the deleterious effect of maternal protein deprivation on cardiac bioenergetics. METHODS AND RESULTS: We used a rat model of maternal protein restriction during gestational and lactation period followed by an offspring treadmill moderate physical training. Pregnant rats were divided into two groups: normal nutrition receiving 17% of casein in the diet and undernutrition receiving a low-protein diet (8% casein). At 30 days of age, the male offspring were further subdivided into sedentary (NS and LS) or exercised (NT and LT) groups. Treadmill exercise was performed as follows: 4 weeks, 5 days/week, 60 min/day at 50% of maximal running capacity. Our results showed that a low-protein diet decreases oxidative metabolism and mitochondrial function associated with higher oxidative stress. In contrast, exercise rescues mitochondrial capacity and promotes a cellular resilience to oxidative stress. Up-regulation of cardiac sirtuin 1 and 3 decreased acetylation levels, redeeming from the deleterious effect of protein restriction. CONCLUSION: Our findings show that moderate daily exercise during a young age acts as a therapeutical intervention opposing the harmful effects of a maternal diet restricted in protein.

Fluoxetine administration in juvenile overfed rats improves hypothalamic mitochondrial respiration and REDOX status and induces mitochondrial biogenesis transcriptional expression.

Nutritional imbalance in early life may disrupt the hypothalamic control of energy homeostasis and increase the risk of metabolic disease. The hypothalamic serotonin (5-hydroxytryptamine; 5-HT) system based in the hypothalamus plays an important role in the homeostatic control of energy balance, however the mechanisms underlying the regulation of energy metabolism by 5-HT remain poorly described. Several crucial mitochondrial functions are altered by mitochondrial stress. Adaptations to this stress include changes in mitochondrial multiplication (i.e, mitochondrial biogenesis). Due to the scarcity of evidence regarding the effects of serotonin reuptake inhibitors (SSRI) such as fluoxetine (FLX) on mitochondrial function, we sought to investigate the potential contribution of FLX on changes in mitochondrial function and biogenesis occurring in overfed rats. Using a neonatal overfeeding model, male Wistar rats were divided into 4 groups between 39 and 59 days of age based on nutrition and FLX administration: normofed + vehicle (NV), normofed + FLX (NF), overfed + vehicle (OV) and overfed + FLX (OF). We found that neonatal overfeeding impaired mitochondrial respiration and increased oxidative stress biomarkers in the hypothalamus. FLX administration in overfed rats reestablished mitochondrial oxygen consumption, increased mitochondrial uncoupling protein 2 (Ucp2) expression, reduced total reactive species (RS) production and oxidative stress biomarkers, and up-regulated mitochondrial biogenesis-related genes. Taken together our results suggest that FLX administration in overfed rats improves mitochondrial respiratory chain activity and oxidative balance and increases the transcription of genes employed in mitochondrial biogenesis favoring mitochondrial energy efficiency in response to early nutritional imbalance.

Chronic serotonin reuptake inhibition uncouples brown fat mitochondria and induces beiging/browning process of white fat in overfed rats.

AIM: To investigate whether a chronic 5-HT reuptake inhibitor (i.e. Fluoxetine-FLX) exposure in young adult rats overfed during suckling period would modulate interscapular brown adipose tissue (iBAT) mitochondria and browning agents in white adipose tissue (WAT). METHODS: Male Wistar rats were assigned into either a normofed group (n = 9 per group) or an overfed group (n = 3 per group) induced by litter size reduction at postnatal day 3 (PND3). Pharmacological manipulation was carried out between PND39 and PND59 and groups were assigned accordingly: Normofed + vehicle solution - NaCl 0.9% (NV group), normofed + FLX solution - 10 mg/kg b.w. (NF group), overfed + vehicle (OV group) and overfed + FLX (OF group). We evaluated mitochondrial oxygen consumption and reactive species (RS) production, oxidative stress analyses (MDA concentration, carbonyl content, REDOX state [GSH/GSSG], global oxy score) in the iBAT, gene (leptin, Ucp1, Sirt1, Pgc1α and Prdm16) and protein (UCP1) expression in the iBAT and epididymal WAT (eWAT). KEY FINDINGS: OV group increased body weight gain, Lee index and oxidative stress in the iBAT. Both FLX-treated groups showed less weight gain compared to their controls. OF group showed different leptin expression in the WAT and iBAT; increased functional UCP1 content and mitochondrial activity with less oxidative stress in the iBAT and upregulation of browning genes in eWAT (Pgc1α, Prdm16 and Ucp1). CONCLUSION: Altogether our findings indicated that FLX treatment in young adult overfed animals improved the iBAT mitochondrial function, reduced oxidative stress and induced transcriptional activation of browning agents in white adipose tissue.

Influence of maternal protein malnutrition on oxidative stress and regulators of mitochondrial biogenesis in female rat hearts over succeeding generations.

AIMS: We sought to evaluate the effects of maternal protein restriction (LP) on oxidative balance and transcription factors for mitochondrial biogenesis in the hearts of young female rats of both the first (F1) and second (F2) generation. MAIN METHODS: We evaluated oxidative stress biomarkers (lipid peroxidation and protein oxidation), enzymatic antioxidant defense (activity of superoxide dismutase-SOD, catalase, and glutathione-S-transferase-GST), nonenzymatic antioxidant defense (reduced glutathione-GSH and sulfhydryl groups) and gene expression of AMPK, PGC-1α and TFAM. KEY FINDINGS: Interestingly, lipid peroxidation was decreased (49%, p < 0.001) in the LP-F1 group and 59% (p < 0.001) in LP-F2. In enzymatic defense, we observed increases in SOD activity in the LP-F1 group (79%, p = 0.036) and in CAT activity (approximately 40%, p = 0.041). GSH was increased in F2 in both groups (LP 546%, p < 0.0001 and in NP 491.7%, p < 0.0001). With respect to mitochondrial biogenesis gene transcription, we observed a decrease in AMPK (60%, p < 0. 0001) and an increase in PGC-1α (340%, p < 0.001) in LP compared to NP in the F1 generation. TFAM was decreased in LP-F2L compared to NP-F2L (42%, p = 0.0069) and increased in LP-F2 compared to LP-F1 (160%, p = 0.0037). SIGNIFICANCE: Our study contributes to knowledge of inheritance, showing that despite the potential mitochondrial 'inheritance' of cardiovascular damage caused by maternal malnutrition, that damage is not cross-generational and can be eliminated with proper nutrition in the F1 generation.

Body composition, biochemical, behavioral and molecular alterations in overfed rats after chronic exposure to SSRI.

Serotonin (5-HT) plays a regulatory role in coordinating the neural circuits regulating energy balance, with differences in both 5-HT availability at the synapse and the activity of 5-HT receptors mediating anorectic (via POMC/CART activation) and orexigenic (via NPY/AgRP activation) responses. In conditions of overweight and obesity the control of energy balance is clearly deregulated, and serotonergic modulation appears to make a significant contribution to weight gain. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) that increases 5-HT availability in the synaptic cleft may thus have potential effects on energy balance. Our aim was to use an overfeeding model to investigate the effects of chronic FLX treatment on energy balance-related parameters regulated by hypothalamic neuropeptides. Nursing male Wistar rats were assigned to normofed (9 pups/dam) or overfed (3 pups/dam) groups beginning at 3 days of age and continuing until 21 days of age, when commercial chow and water were made available ad libitum until experimental treatments were begun. From 39 through 59 days of age groups were divided according to pharmacological treatment: 1) NV group, normofed + vehicle solution (NaCl 0.9%, 10 ml/kg b.w.), 2) NF group, normofed + FLX (10 mg/kg b.w., in vehicle solution, 10 ml/kg b.w.) 3), OV, overfed + vehicle solution and 4) OF, overfed + FLX. At 60 days of age, body weight, white and brown adipose tissue content, and food intake were determined, and serum biochemical parameters and hypothalamic neuropeptide gene expression were measured. Results showed that FLX induced reductions in several murinometric indices, improvement of adipose profile, hypophagic behavior, reduction in serum parameters, and positive modulation of hypophagia-related genes. These data suggest that the beneficial effects of FLX-treatment on overfeeding-induced physical and behavioral effects in rats was due to hypothalamic alterations that led to improvement in energy balance in animals with a compromised metabolism.

Serotonin transporter inhibition during neonatal period induces sex-dependent effects on mitochondrial bioenergetics in the rat brainstem.

The serotonin reuptake is mainly regulated by the serotonin transporters (SERTs), which are abundantly found in the raphe nuclei, located in the brainstem. Previous studies have shown that dysfunction in the SERT has been associated with several disorders, including depression and cardiovascular diseases. In this manuscript, we aimed to investigate how gender and the treatment with a serotonin selective reuptake inhibitor (SSRI) could affect mitochondrial bioenergetics and oxidative stress in the brainstem of male and female rats. Fluoxetine, our chosen SSRI, was used during the neonatal period (i.e., from postnatal Day 1 to postnatal Day 21-PND1 to PND21) in both male and female animals. Thereafter, experiments were conducted in adult rats (60 days old). Our results demonstrate that, during lactation, fluoxetine treatment modulates the mitochondrial bioenergetics in a sex-dependent manner, such as improving male mitochondrial function and female antioxidant capacity.

Mitochondrial bioenergetics and oxidative status disruption in brainstem of weaned rats: Immediate response to maternal protein restriction.

Mitochondrial bioenergetics dysfunction has been postulated as an important mechanism associated to a number of cardiovascular diseases in adulthood. One of the hypotheses is that this is caused by the metabolic challenge generated by the mismatch between prenatal predicted and postnatal reality. Perinatal low-protein diet produces several effects that are manifested in the adult animal, including altered sympathetic tone, increased arterial blood pressure and oxidative stress in the brainstem. The majority of the studies related to nutritional programming postulates that the increased risk levels for non-communicable diseases are associated with the incompatibility between prenatal and postnatal environment. However, little is known about the immediate effects of maternal protein restriction on the offspring's brainstem. The present study aimed to test the hypothesis that a maternal low-protein diet causes tissue damage immediately after exposure to the nutritional insult that can be assessed in the brainstem of weaned offspring. In this regard, a series of assays was conducted to measure the mitochondrial bioenergetics and oxidative stress biomarkers in the brainstem, which is the brain structure responsible for the autonomic cardiovascular control. Pregnant Wistar rats were fed ad libitum with normoprotein (NP; 17% casein) or low-protein (LP; 8% casein) diet throughout pregnancy and lactation periods. At weaning, the male offsprings were euthanized and the brainstem was quickly removed to assess the mitochondria function, reactive oxygen species (ROS) production, mitochondrial membrane electric potential (ΔΨm), oxidative biomarkers, antioxidant defense and redox status. Our data demonstrated that perinatal LP diet induces an immediate mitochondrial dysfunction. Furthermore, the protein restriction induced a marked increase in ROS production, with a decrease in antioxidant defense and redox status. Altogether, our findings suggest that LP-fed animals may be at a higher risk for oxidative metabolism impairment throughout life than NP-fed rats, due to the immediate disruption of the mitochondrial bioenergetics and oxidative status caused by the LP diet.

Serotonin modulation in neonatal age does not impair cardiovascular physiology in adult female rats: Hemodynamics and oxidative stress analysis.

AIMS: The present study investigates the effects of neonatal serotonin modulation in female rats on cardiac parameters related to hemodynamics and oxidative metabolism in the mature animal. MAIN METHODS: Female Wistar rat pups were administered daily subcutaneous injections of fluoxetine (Fx-treated group) or vehicle solution (Ct-group) from the 1st to 21st day of life. At 60days of age, animals from both groups were either used for cardiovascular evaluation or sacrificed for tissue collection for biochemical assays. KEY FINDINGS: We found that body weight in the Fx-treated group was less than that in the control. When analyzing hemodynamic parameters (i.e., arterial blood pressure, heart rate-HR, sympathetic and vagal tonus, or intrinsic HR), we did not observe significant difference in the Fx-treated group. Evaluating oxidative stress in brainstem and heart by measuring carbonyl content and malondialdehyde-MDA formation, we observe a decrease in carbonyl content only in the Fx-treated group (60.3%, in brainstem; 58.2%, in heart), without difference in the MDA levels. This observation is consonant with an increase in superoxide dismutase-SOD and catalase-CAT activity in brainstem and heart in the Fx-treated group (SOD: 82.7% and CAT: 23.7 in brainstem; SOD: 60.6%, and CAT: 40.7 in heart), with no changes in glutathione S-transferase activity and reduced glutathione levels. With regard to oxidative metabolism markers, citrate synthase activity was higher in brainstem in the Fx-treated group (20%). SIGNIFICANCE: Our data suggest that serotonin modulation by Fx-treatment at an early age does not induce hemodynamic alteration, although it modulates oxidative metabolism in cardiac-related tissues.

Can fish oil supplementation and physical training improve oxidative metabolism in aged rat hearts?

AIMS: It is well known that in the aging process a variety of physiological functions such as cardiac physiology and energy metabolism decline. Imbalance in production and elimination of reactive oxygen species (ROS) may induce oxidative stress. Research shows that oxidative stress is an important factor in the aging process. Studies suggest that É·-3 polyunsaturated fatty acids (PUFAs) and moderate physical exercise modulate the ROS system. Therefore, the present study aimed to investigate whether É·-3 present in fish oil supplementation coupled with moderate physical training could improve antioxidant and metabolic enzymes in the hearts of adult and aged rats and, if these effects could be associated to glycemia, plasma lipid profile or murinometric parameters. MAIN METHODS: Adult (weighing 315.1±9.3g) and aged rats (weighing 444.5±11.8g) exercised and receive fish oil supplementation for 4weeks. Then they were used to evaluate murinometric parameters, fasting glucose and lipid profile. After this, their hearts were collected to measure the levels of malondialdehyde (MDA), antioxidant enzyme activity (superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx) and oxidative metabolism marker (citrate synthase-CS activity). KEY FINDINGS: Fish oil supplementation increases HDL concentration and activity of CAT and CS. Moreover, physical training coupled with fish oil supplementation induces additional effects on SOD, GPx and CS activity mainly in aged rats. SIGNIFICANCE: Our data suggest that combined treatment in aged rat hearts improves the antioxidant capacities and metabolic enzyme that can prevent the deleterious effects of aging.

Effect of moderate exercise on peritoneal neutrophils from juvenile rats.

Previous studies showed that moderate exercise in adult rats enhances neutrophil function, although no studies were performed in juvenile rats. We evaluated the effects of moderate exercise on the neutrophil function in juvenile rats. Viability and neutrophils function were evaluated. Moderate exercise did not impair the viability and mitochondrial transmembrane potential of neutrophils, whereas there was greater reactive oxygen species production (164%; p < 0.001) and phagocytic capacity (29%; p < 0.05). Our results suggest that moderate exercise in juvenile rats improves neutrophil function, similar to adults.

Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues.

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.

The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress.

Protein restriction during perinatal and early postnatal development is associated with a greater incidence of disease in the adult, such arterial hypertension. The aim in the present study was to investigate the effect of maternal low-protein diet on mitochondrial oxidative phosphorylation capacity, mitochondrial reactive oxygen species (ROS) formation, antioxidant levels (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the adult offspring. Pregnant Wistar rats received either 17% casein (normal protein, NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After weaning male progeny of these NP or LP fed rats, females were maintained on commercial chow (Labina-Purina). At 100 days post-birth, the male rats were sacrificed and heart tissue was harvested and stored at -80 °C. Our results show that restricting protein consumption in pregnant females induced decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP-stimulated oxygen consumption and 49.5% reduction in respiratory control ratio) in their progeny when compared with NP group. In addition, maternal low-protein diet induced a significant decrease in enzymatic antioxidant capacity (37.8% decrease in superoxide dismutase activity; 42% decrease in catalase activity; 44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and glutathione level (34.8% decrease) when compared with control. From these findings, we hypothesize that an increased production of ROS and decrease in antioxidant activity levels induced by protein restriction during development could potentiate the progression of metabolic and cardiac diseases in adulthood.