Physical Exercise During Pregnancy Prevents Cognitive Impairment Induced by Amyloid-β in Adult Offspring Rats

Abstract

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.

Effect of maternal antioxidant supplementation and/or exercise practice during pregnancy on postnatal overnutrition induced by litter size reduction: Brain redox homeostasis at weaning

“…Modifying the lifestyle during pregnancy may positively affect the developmental programming, protecting the offspring against metabolic dysfunctions (Klein et al, 2018; Mathias et al, 2014; Bambini‐Junior et al, 2014). In the present study, we aimed to assess the potential preventive effect of maternal exercise and maternal naringenin supplementation, isolated or in combination, on metabolic alterations in the offspring, at 21 days of age, induced by postnatal overnutrition induced by the litter size reduction model.…”

Protective effect of maternal exercise against amyloid-β neurotoxicity in the male rat offspring’s cerebellum

“…well as metabolic alterations in the prefrontal cortex and hippocampus of young adult male rat offspring. 8 In the present study, we extended the investigation to cerebellum and observed that maternal exercise during pregnancy promotes adaptive response in developing fetuses through programming cerebellar neurochemistry that remains evident into young adulthood. Importantly, maternal exercise-induced programming was able to prevent some pathologic consequences of AβO peptide infusion, including rise of RS, protein carbonylation, and phosphorylation of tau protein.…”

“…3 The phenotype shaping of the developing metabolism is established through plastic processes that enable an adaptation to environment 4 by metabolic programming, 5 which rely on epigenetic alterations that modulate gene expression and oxidative environment. 6 We and others have demonstrated that maternal exercise during pregnancy improves brain antioxidant defense system 7 and induces mitochondrial biogenesis 7,8 in 7-day-old rats, improves glucose homeostasis and insulin sensitivity in adult mice (>6 weeks old), 9 and neurogenesis in newborn rats 10 and young mice, 11 as well as increases brain-derived neurotrophic factor (BDNF) levels in the brain of young 10 and adult 12 rats. These findings highlight maternal exercise as a modulator of intrauterine environment that favors enhanced brain function.…”

“…[20][21][22][23] Although human and animal studies have shown that physical exercise during pregnancy improves several brain functions and cognitive performance of the offspring, 10,[24][25][26][27][28] few studies have addressed the beneficial effects of maternal exercise during pregnancy regarding neuroprotective role against neurodegeneration in the offspring at adult age. 8,14 The hallmarks of AD are the amyloid-β (Aβ) peptide accumulation and intracellular neurofibrillary tangles that lead to neuronal damage. 29 In addition, events including oxidative stress, mitochondrial dysfunction, energetic metabolism failure, and neuroinflammation are suggested to be part of the underlying molecular mechanisms of the disease.…”

Adaptive effects of gestational caloric restriction in the mitochondria of Wistar rats' brain: A DOHaD approach

“…This concept evolved from Barker's studies on the thrifty phenotype, or Barker's hypothesis (Barker et al, 1989). Our group already showed how several different interventions may influence the offspring health when applied during pregnancy, such as Caloric Restriction (CR) (Stone et al, 2019), food restriction (FR) (Stone et al, 2016), high‐salt diet (Stocher et al, 2018), polyphenol supplementation (August et al, 2018), and swimming exercise (August et al, 2018; Klein et al, 2018, 2019; Marcelino et al, 2013).…”