Exercício físico materno altera a função mitocondrial e o estado redox no músculo esquelético da prole de ratas Wistar

A gestação é um período fundamental do desenvolvimento fetal. Diversos estudos demonstram que o ambiente intrauterino, ao qual o feto é exposto, pode causar modulações benéficas ao organismo da prole. Assim, de acordo com o conceito das Origens Desenvolvimentistas da Saúde e da Doença, o desenvolvimento de diversas doenças, ao longo da vida, tem como origem alterações causadas durante o período intrauterino. Considerando que existem evidências de que o exercício físico materno durante a gestação é capaz de causar alterações benéficas no organismo da prole, o objetivo desse estudo foi avaliar o desenvolvimento pós-natal (neuromotor e anatômico), bem como a função mitocondrial e o estado redox no músculo esquelético da prole. Para tanto, ratas Wistar adultas foram divididas em 3 grupos distintos: (1) sedentário, (2) exercício e (3) exercício com sobrecarga (2% peso corporal). Os grupos exercitados realizaram exercício de natação 30 min/dia, 5 dias/semana, iniciando uma semana antes do acasalamento até o final do período gestacional. Avaliamos na prole o desenvolvimento neuromotor através dos testes de endireitamento de superfície, geotaxia negativa, aversão à queda e suspensão em barra, bem como o desenvolvimento anatômico através da avaliação do peso, dia de abertura dos olhos e ouvido externo, aparecimento dos dentes incisivos superiores, desenvolvimento do pelo nos filhotes machos e fêmas. Também avaliamos o conteúdo e a função mitocondrial e o estado redox, por meio da avaliação de defesas antioxidantes, bem como níveis de oxidantes e dano a proteínas na prole com 60 dias de vida. Nossos resultados não mostraram diferenças estatisticamente significativas para nenhum dos parâmetros neuromotores e anatômicos avaliados na prole. Por outro lado, para o conteúdo e a função mitocondrial, foi demonstrado um aumento nos machos e fêmeas, prole das ratas exercitadas com sobrecarga. Também observamos diferenças sexo-dependentes no estado redox entre machos e fêmeas prole das ratas exercitadas com sobrecarga durante a gestação. Em conclusão, o exercício físico em intensidade moderada, realizado durante a gestação, não acelera nem retarda o desenvolvimento anatômico e motor da prole. Todavia, o exercício físico em intensidade moderada durante a gestação aumenta o conteúdo e a atividade mitocondrial diferentemente entre machos e fêmeas, além de modular de maneira sexo-dependente o estado redox muscular da prole. Esses dados reforçam a importância de realização de exercício físico antes e durante a gestação, a fim de trazer benefícios à prole.Pregnancy is an important developmental period to the fetus. In accordance to the Developmental Origins of Health and Disease, the development of several diseases throughout offspring life originates by alterations during the intrauterine period. Considering that evidence suggests that maternal exercise during pregnancy can modulate the offspring organism in a beneficial way, our aim was to evaluate the post-natal neuro and anatomical development, the mitochondrial function and content, as well as the redox status on the adult offspring skeletal muscle. Adult female Wistar rats were divided into three groups: (1) sedentary, (2) exercise, and (3) overload exercise group (addiction of 2% corporal weight load). The exercised groups swam 30 mins/day, 5 days/week, one week before and throughout the pregnancy. We evaluated the neuromotor development through the surfacing righting, negative geotaxis, cliff avoidance and bar holding tests, so as the anatomical development through the evaluation of the weight, eyes opening day, pinna detachment, superior incisors eruption and fur development on male and female offspring. We also evaluated the mitochondrial function and content, and the redox status by antioxidant profile, total oxidant levels and protein damage. We observed no statistically differences between the groups or between sex in any of the neuromotor and physical landmark observations. Concerning to the mitochondrial function and content, we observed an improvement in the male and female pups born from overload exercised mothers. In addition, we also observed sex-dependent modulations in the redox status between male and female pups born from overload exercised mothers. In conclusion, moderate intensity exercise during pregnancy do not accelerate or delay neuromotor and anatomical development on the offspring. On the other hand, physical exercise during pregnancy increased mitochondrial content and function in the skeletal muscle, and modulated the redox status on the offspring in a sex-dependent way. Our date reinforces the importance of maternal exercise, bringing health benefits to the next generation

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

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

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.This study was supported by the Pró-Reitoria de Pesquisa/Universidade Federal do Rio Grande do Sul (PROPESQ/UFRGS). CPK is a PhD Postgraduate student in Biological Sciences – Biochemistry receiving grants from the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). CM received grants from CNPq (Universal 442406/2014-2 and INCT 465671/2014-4)