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.

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.

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.

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Several environmental factors affect child development, such as the intrauterine environment during the embryonic and fetal development and early postnatal environment provided by maternal behavior. Although mechanistic effects of maternal exercise on offspring health improvement are not yet completely understood, the number of reports published demonstrating the positive influence of maternal exercise have increase. Herein, we addressed issues related to early postnatal environment provided by maternal behavior and early developmental physical landmarks, sensorimotor reflexes, and motor movements ontogeny. In brief, adult female rats underwent involuntary swimming exercise, in a moderated intensity, one week before mating and throughout pregnancy, 30 min a day, 5 days a week. Maternal exercised dams have unchanged gestational outcomes compared to sedentary dams. We found no differences concerning the frequency of pup-directed behavior displayed by dams. However, sedentary dams displayed a poorer pattern of maternal care quality during dark cycle than exercised dams. Physical landmarks and sensorimotor reflexes development of female and male littermates did not differ between maternal groups. Developmental motor parameters such as immobility, lateral head movements, head elevation, pivoting, rearing with forelimb support and crawling frequencies did not differ between groups. Pups born to exercised dams presented higher frequency of walking and rearing on the hind legs. These data suggest that female and male littermates of exercised group present a high frequency of exploratory behavior over sedentary littermates. Taken together, the present findings reinforce that maternal exercise throughout pregnancy represent a window of opportunity to improve offspring's postnatal health.