Effects of maternal low-protein diet and spontaneous physical activity on the transcription of neurotrophic factors in the placenta and the brains of mothers and offspring rats.

Maternal protein restriction and physical activity can affect the interaction mother-placenta-fetus. This study quantified the gene expression of brain-derived neurotrophic factor (BDNF), neurothrophin 4, tyrosine kinase receptor B (TrkB/NTRK2), insulin-like growth factor (IGF-1), and insulin-like growth factor receptor (IGF-1r) in the different areas of mother's brain (hypothalamus, hippocampus, and cortex), placenta, and fetus' brain of rats. Female Wistar rats (n = 20) were housed in cages containing a running wheel for 4 weeks before gestation. According to the distance spontaneously traveled daily, rats were classified as inactive or active. During gestation, on continued access to the running wheel, active and inactive groups were randomized to receive normoprotein diet (18% protein) or a low-protein (LP) diet (8% protein). At day 20 of gestation, gene expression of neurotrophic factors was analyzed by quantitative polymerase chain reaction in different brain areas and the placenta. Dams submitted to a LP diet during gestation showed upregulation of IGF-1r and BDNF messenger RNA in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, and BDNF, NTRK2, IGF-1 and IGF-1r in the cortex. In the placenta, there was a downregulation of IGF-1. In the brain of pups from mothers on LP diet, IGF-1r and NTRK2 were downregulated. Voluntary physical activity attenuated the effects of LP diet on IGF-1r in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, IGF-1 in the placenta, and NTRK2 in the fetus' brain. In conclusion, both maternal protein restriction and spontaneous physical activity influence the gene expression of BDNF, NTRK2, IGF-1, and IGF-1r, with spontaneous physical activity being able to normalize in part the defects caused by protein restriction during pregnancy.

Can the frequency of defensive posture adoption influence the expression of active behavior of adult rats?

During the youth, rats spend a long time in play fighting (PF), and asymmetries are observed in terms of the frequency of adoption of the supine posture. This study investigated the effects of asymmetry in adopting supine posture during PF on the time spent in locomotor activity-related contextual behaviors during youth and adulthood. Male Wistar rats were divided into three groups according to the number of times of their adoption of a defensive supine (S) posture: low (LS, n = 10), intermediary (IS, n = 10) and high (HS, n = 10). Rats aged 21-62 days were placed in voluntary physical active cages (VPAC) with running wheels. The time spent in social play (SP), play fighting (PF), voluntary physical activity (VPA), spontaneous physical activity (SPA) and resting (Rest) were recorded daily. During adulthood (63-92 days of age), rats were placed individually in the VPAC, with daily quantification of VPA. The average time spent in PF was not different among the groups, but was age-dependent. LS and IS rats spent more time in VPA than the HS rats, between days 49-62 (intragroup analyses) and 72-78 (individual analyses) days of age. However, LS and IS animals spent less time in SPA than HS rats from 42-48 days of age. In conclusion, the expressions of VPA and SPA are influenced by the asymmetries in adoption of the supine posture of members within a social group, remaining even after the separation of the social groups.

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring.

Maternal physical activity induces brain functional changes and neuroplasticity, leading to an improvement of cognitive functions, such as learning and memory in the offspring. This study investigated the effects of voluntary maternal physical activity on the gene expression of the neurotrophic factors (NTFs): BDNF, NTF4, NTRK2, IGF-1 and IGF-1r in the different areas of mother's brain, placenta and foetus brain of rats. Female Wistar rats (n = 15) were individually housed in voluntary physical activity cages, containing a running wheel, for 4 weeks (period of adaptation) before gestation. Rats were classified as inactive (I, n = 6); active (A, n = 4) and very active (VA, n = 5) according to daily distance spontaneously travelled. During gestation, the dams continued to have access to the running wheel. At the 20th day of gestation, gene expression of NTFs was analysed in different areas of mother's brain (cerebellum, hypothalamus, hippocampus and cortex), placenta and the offspring's brain. NTFs gene expression was evaluated using quantitative PCR. Very active mothers showed upregulation of IGF-1 mRNA in the cerebellum (36.8%) and NTF4 mRNA expression in the placenta (24.3%). In the cortex, there was a tendency of up-regulation of NTRK2 mRNA (p = 0.06) in the A and VA groups when compared to I group. There were no noticeable changes in the gene expression of NTFs in the offspring's brain. Our findings suggest the existence of a developmental plasticity induced by maternal physical activity in specific areas of the brain and placenta representing the first investment for offspring during development.

Maternal voluntary physical activity attenuates delayed neurodevelopment in malnourished rats.

NEW FINDINGS: What is the central question of this study? In the present study, a reproducible model of maternal voluntary physical activity was developed to evaluate the adaptive response of physical activity by attenuating the effects of maternal undernutrition on physical features, reflex ontogeny and growth trajectory of offspring during development. What is the main finding and its importance? Maternal physical activity may induce neuronal maturation of sensorimotor connections impacting on the patterns of locomotor activity in malnourished offspring. Thus, physical activity should be considered as a therapeutic means of countering the effects of maternal undernutrition, by providing a useful strategy for enhancing the neuronal activity of children born to mothers who experience a restricted diet during pregnancy. This study evaluated the effects of maternal voluntary physical activity during pregnancy and lactation on somatic growth (SG), reflex ontogeny (RO) and locomotor activity (LA) of rats whose mothers were protein restricted. Virgin female Wistar rats were divided into the following six groups: control, normal protein (C-NP, n = 4); control, low protein (C-LP, n = 4); inactive, normal protein (I-NP, n = 8); inactive, low protein (I-LP, n = 7); very active, normal protein (VA-NP, n = 8); and very active, low protein (VA-LP, n = 6). Voluntary physical activity was recorded daily in dams. The LP groups were fed an 8% casein diet, whereas control groups were fed a 17% casein diet during pregnancy and lactation. Offspring were evaluated in terms of SG (body weight and length, latero-lateral skull axis and anteroposterior head axis) and RO (palmar grasp, righting, free-fall righting, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing). The LA was evaluated at 23, 45 and 60 days old in the open field. Voluntary physical activity was reduced during pregnancy and lactation independent of the maternal diet. Pups from LP dams showed delayed SG, reflex maturation and patterns of LA when compared with control pups. The C-LP and I-LP pups showed a delayed SG, RO and LA. Pups from VA-LP mothers showed no delay in SG and RO and presented a faster development of patterns of LA. Maternal voluntary physical activity attenuated the effects of LP diet on indicators of neurodevelopment and patterns of LA of offspring.

New Insights on the Maternal Diet Induced-Hypertension: Potential Role of the Phenotypic Plasticity and Sympathetic-Respiratory Overactivity.

Systemic arterial hypertension (SAH) is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural, and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental stimuli without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity.

Active maternal phenotype is established before breeding and leads offspring to align growth trajectory outcomes and reflex ontogeny.

The main goals of this study were to classify dams according to the level of voluntary physical activity before breeding and during pregnancy/lactation and to evaluate the effects on growth trajectory and reflex ontogenesis of offspring. Voluntary physical activity was ranked by traveled distance, time and daily estimated calorie burned. Thirty-five female Wistar rats were classified as control (C, n=5), inactive (I, n=10), active (A, n=8) and very active (VA, n=12). During 30d before breeding, traveled distance, average speed, time and calorie burned were daily recorded for active and very active groups. Traveled distance was recorded each 2h every day of adaptation. Body weight, food intake and fasting glycemia were measured throughout the experiment. During lactation, litters were evaluated in terms of physical features and reflex ontogeny. VA showed a progressive increase in the traveled distance and time while A dams presented constant values. VA rats showed lower body weight and higher food intake. During pregnancy, both groups performed less than 1km/day. Pups from A and VA dams showed higher lateral-lateral axis of the skull, longitudinal axis, tail length, and anticipation of the pavilion and auditory canal opening, and erupting incisors. I, A and VA groups showed a delay of righting, cliff aversion and vibrissae placing reflexes. In conclusion, active maternal phenotype is established before breeding allowing mothers to fit ecological and influencing growth trajectory outcomes and reflex ontogeny of the offspring based on matrilineal experience.