Does the enriched environment alter memory capacity in malnourished rats by modulating BDNF expression?

Environmental factors interfere in the neural plasticity processes. Among these, malnutrition in the early stages of life stands out as one of the main non-genetic factors that can interfere in the morphofunctional development of the nervous system. Furthermore, sensory stimulation from enriched environments (EE) also interferes with neural development. These two factors can modify areas related to memory and learning as the hippocampus, through mechanisms related to the gene expression of brain-derived neurotrophic factor (BDNF). The BDNF may interfere in synaptic plasticity processes, such as memory. In addition, these changes in early life may affect the functioning of the hippocampus during adulthood through mechanisms mediated by BDNF. Therefore, this study aims to conduct a literature review on the effects of early malnutrition on memory and the relationship between the underlying mechanisms of EE, BDNF gene expression, and memory. In addition, there are studies that demonstrate the effect of EE reversal on exposure to changes in the functioning of hippocampal malnutrition in adult rats that were prematurely malnourished. Thereby, evidence from the scientific literature suggests that the mechanisms of synaptic plasticity in the hippocampus of adult animals are influenced by malnutrition and EE, and these alterations may involve the participation of BDNF as a key regulator in memory processes in the adult animal hippocampus.

Pre-weaning maternal separation increases eating later in life in male and female offspring, but increases brainstem dopamine receptor 1a and 2a only in males.

Maternal separation stress (MS) is a model of early life stress performed by the separation between dam and pups in the first days of life. This model has been associated with eating behavior and dopaminergic system abnormal phenotypes. This study aims to investigate whether maternal separation in the light or dark phase of the circadian cycle promotes phenotypic adjustments in the eating behavior and the dopamine system in both males and females. Lactating Wistar rats were separated from their litters from postnatal day 1 (PND 1) to PND 14 for 6 h in the light or dark phase of the circadian cycle. The groups of female control (FC), male control (MC), female rat separated in the dark (FSD), male rat separated in the dark (MSD), female rat separated in the light (FSL), and male rat separated in the light (MSL) were composed. The assessment of food intake was performed at the age of 120-150 days and the analysis of brainstem drd1a and drd2a dopamine receptors expression at 180 days of life. Maternal separation promoted higher palatable diet intake independent on sex and circadian cycle. On the other hand, drd1a and drd2a dopamine receptors expression were higher only in males separated in the dark phase of the circadian cycle. These findings demonstrate that maternal separation effects on feeding behavior do not depend on sex and circadian cycle, but the effects on dopamine receptors expression depend on sex and circadian cycle.

Undernutrition during pregnancy and lactation increases the number of fos-cells in the reward system in response to a 5-HT6 receptor agonist in male adolescent rats.

Undernutrition promotes morphofunctional adaptations in neuroanatomical circuits, leading to behavioural changes. Adolescence is a period of vulnerability for these adaptations, such as the control of food intake and the serotonergic system. The serotonergic system is capable of promoting satiety. However, its role in hedonic control has not been fully elucidated. The involvement of the 5-HT6 receptor in motivational feeding behaviours was recently observed. Therefore, we aimed to evaluate the effect of a 5-HT6 receptor agonist on food intake and neuronal activation in areas of the reward system in adolescent rats subjected to perinatal protein undernutrition. Wistar rats were divided into two groups according to nutritional manipulation during gestation and lactation. It has been observed that undernourished animals present greater neuronal activation in response to the 5HT-6 receptor agonist in areas of the food reward system.

Relationship between vitamin B12 levels and motor development: A systematic review.

BACKGROUND AND OBJECTIVES: Nutrition plays a crucial role in the development and health of the human brain, from early stages to adulthood. The complex process of neurodevelopment necessitates interaction among various factors, with balance in the concentration of vital macronutrients and micronutrients being essential. Regarding micronutrients, vitamin B12 stands out, playing a vital role in the development and functioning of the motor nervous system. The objective was to investigate the influence of reduced levels of vitamin B12 on infant motor development and analyze the effects of supplementation on this aspect of development. METHODS: For this purpose, the criteria of the PRISMA method and registration in the PROSPERO database were used. The search was conducted in the following databases: PubMed (Medline), Scopus, PsycINFO, Web of Science, and ScienceDirect. A total of 684 records were initially identified. RESULTS: Of the eight included articles, there was diversity regarding geographical contexts and study designs. The final sample comprised a total of 1,559 participants of both sexes. Studies aimed at correcting low levels of vitamin B12 opted for supplementation, following various protocols that varied in dose, administration method, and duration. At the end of the studies, the serum level of this vitamin ranged from 131 pmol/L to 1141 pmol/L. CONCLUSION: There is a complex array of factors contributing to reduced levels of vitamin B12, especially in the early stages of life, which significantly impacts infant motor development. Despite methodological variations among studies, evidence suggests that low levels of vitamin B12 may affect motor development and that supplementation could be an effective means of enhancing motor aspects in healthy children. However, due to the diversity of outcomes, it is important to promote comprehensive public policies to encourage appropriate interventions in this area.

Early-life undernutrition and depression later in life: a systematic review.

CONTEXT: Early adverse experience can have a long-term effect on growth and development and negative repercussions into adulthood. Among the various consequences of undernutrition is depression. OBJECTIVE: The present work aimed to evaluate the relationship between early-life undernutrition and depression in adult life. DATA SOURCES: Data were obtained from the PubMed, SCOPUS, and Web of Science databases in November 2021 and were selected using the systematic bibliographic review manager program State of the Art Through Systematic Review. DATA EXTRACTION: Data were extracted using the State of the Art Through Systematic Review program. DATA ANALYSIS: Of the 559 articles that were identified, 114 were duplicates, and 426 were excluded after inclusion and exclusion criteria were applied to the title and abstract. One other relevant study was included. From the 20 remaining articles, 8 were excluded after the full-text screening. Finally, 12 articles remained for review in the present work. The studies described in these articles investigated humans, rats, or mice, and correlated early-life malnutrition and depression in adulthood as the principal outcome. CONCLUSIONS: Undernutrition in early life and later depression are linked. Furthermore, the knowledge that the risk factors for depression start at the beginning of life points to public health policies starting in intrauterine life and extending throughout childhood and adolescence.

Therapeutic advances for treating memory impairments in perinatal brain injuries with implications for cerebral palsy: a systematic review and meta-analysis of preclinical studies.

Cerebral palsy (CP) is a neurodevelopmental disorder caused by damage to the immature brain. CP is considered the main cause of physical disability in childhood. Studies have shown that memory function and emotional behaviour are significantly impaired in CP. Current thought is that interventions for neuromotor damaged play a prominent role, but neglects the memory acquisition problems that affect the functioning and quality of life of these children. This systematic review aims to map and analyse pre-clinical interventions used to treat memory formation problems resulting from CP. For this, a search was carried out in the Pubmed, Web of Science, Scopus and Lilacs databases. Then, eligibility, extraction date and evaluation of the methodological quality of the studies were determined. 52 studies were included in this review, and 27 were included in a meta-analysis. Assessing memory performance as a primary outcome, and structural and biochemical changes in the hippocampus as a secondary outcome. CP models were reported to be induced by hypoxia-ischemia, oxygen deprivation and liposaccharide (LPS) exposure, resulting in impairments in the formation of short-term and long-term memory in adult life. A reduction in escape latency and dwell time were observed in the target quadrant as well as an increase in the time needed for the rodents to find the platform in the Morris Water Maze (MWM). Brain injuries during the perinatal period are considered an insult that negatively impacts hippocampus maturation and causes impairment in memory formation in adult life. Some studies reported that regions of the hippocampus such as the dentate gyrus and cornu ammonis 1 were impaired in CP, noting an increase in oxidative stress enzymes and pro-inflammatory cytokines, associated with a reduction in BDNF and neurogenesis levels. These were reported to cause a reduction in the number of neurons and the volume of the hippocampus, in addition to an increase in astrogliosis and apoptosis of neurons and difficulties in forming new memories similar to those that occur in children with CP. Interventions that reduced neuroinflammation and the presence of free radicals were highlighted as a therapy for the memory disturbance present in CP. Preclinical studies registered treatments with oxygen interventions, resveratrol and erythropoietin, which were able to reduce the damage to the hippocampus and promote improvements in memory and behaviour. In the meta-analysis of selected studies, we observed favorable results, through effect size, for the use of oxygen interventions (SDM -6.83 95% CI [-7.91, -5.75], Z = 12.38, p = 0.03; I2 = 71%), erythropoietin (SDM -3.16 95% CI [-4.27, -2.05], Z = 5.58, p = 0.002; I2 = 82%) and resveratrol (SDM -2.42 95% CI [-3.19, - 1.66], Z = 6.21, p = 0.01; I2 = 77%), stimulating plastic responses in the hippocampus and facilitating the memory formation, with these presenting positive effects in general (SDM -2.84 95% CI [-3.10, -2.59], Z = 22.00; p < 0.00001; I2 = 92.9%). These studies demonstrate possible avenues of intervention for memory alterations in experimental models of early brain injuries, highlighting promising interventions that can facilitate the maturation of the hippocampus and memory formation and, consequently, minimize functional problems that arise during development.

Maternal separation in the light or dark phase of the circadian cycle has different effects on the corticosterone levels and anxiety-like behavior in male adult rats.

Maternal care in early life is essential for the growth and development of an offspring. The light phase of the circadian cycle is the dam's most caring phase for her pups. Therefore, we hypothesized that, in the long term, maternal separation (an early-life stress model) in the light phase can be more deleterious than maternal separation in the dark phase. This study aims to compare the effects of maternal separation in the dark or light phase of the circadian cycle on the behavioral and physiological parameters of adult male Wistar rats. From the first to the fourteenth day of life, litters were separated from their mothers for six hours, forming the following experimental groups: Control (C), Maternal Separation in the Light (MSL), and Maternal Separation in the Dark (MSD). After weaning, these groups were left undisturbed until the start of behavioral tests in adulthood. Behavioral measures (standard diet intake, palatable diet intake, and anxiety-like behavior in the elevated plus maze), as well as retroperitoneal adipose tissue weight, and corticosterone levels in response to feeding stress, were assessed between the ages of 120 and 180 days. The results showed that, in adulthood, the food intake after an eight-hour fast or feeding stress had not changed. Anxiety behavior was analyzed by measuring time in the open or closed arms of the elevated plus-maze. The corticosterone levels were measured after food stress, and quantified by using the enzyme-linked immunosorbent assay (ELISA) method. The retroperitoneal adipose tissue weight was also measured. The MSD group presented higher corticosterone levels (MSD = 173.9 ± 12.7) when compared to the C (4.21 ± 0.3) and MSL (4.25 ± 0.28, p < 0.001) groups. In the anxiety test, we observed that the duration in the open arm was shorter for the MSL group (27.4 ± 3.7) compared to the control (112.9 ± 9.6, p < 00.1). There was no change in the MSD group compared to the control, with regard to the time spent in the open arm of the maze. An effect of maternal separation on the consumption of a palatable diet was observed. There was an increase in the palatable diet intake in the MSL (16.3 ± 1.9) and MSD (15.7 ± 0.5) groups compared to the control (11.4 ± 1.2, p < 0.05). In response to stress and food deprivation, there was no difference between groups in food consumption. The adipose tissue weight was higher in the MSD group (7.12 ± 0.29) compared to the control (4.21 ± 0.3) and MSL (4.25 ± 0.28, p < 0.001) groups. Based on the results observed, we concluded that the light-phase stress is more detrimental to emotional behavior during the first two weeks of life, and the dark-phase stress is more detrimental to Hypothalamus-Pituitary-Adrenal (HPA)-axis functioning. Furthermore, the higher intake of a palatable diet could be interpreted as a coping behavior to these early stress-related modifications.

Effects of Overweight/Obesity on Motor Performance in Children: A Systematic Review.

Childhood obesity is a serious public health problem. Childhood obesity and overweight are associated with the appearance of coordination deficit disorder and can cause impaired motor performance. We searched online databases for all related articles using comprehensive international databases from the Medline PubMed Institute, Web of Science, ScienceDirect, SCOPUS, and PsycINFO up to December 20, 2020. Overall, 33 studies were included in this systematic review. The present review demonstrated that children with higher percentage of body fat had lower levels of moderate to vigorous physical activity, as well as decreased levels of gross motor coordination, as shown by tests for neuromuscular performance. These results corroborate the hypothesis that overweight and obesity in children and adolescents are associated, not only with insufficient performance during gross motor coordination activities, but also with a greater risk to physical health. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020182935].

Blockade of Opiodergic System During Early Weaning Reverts Feeding Behavior Altered Patterns.

Adverse experiences that occur during the early stages of life can have permanent repercussions in adulthood. Among these experiences, early weaning is one that can alter the molecular, cellular, and behavior patterns in later life. Centered on this fact, the objective of the current study was to evaluate the effect of early weaning at 15 days of life of Wistar rats on their feeding behavior and if the opioidergic system blockade would cause a reversal of these outcomes. Experimental groups were formed based on the weaning period of each litter. On postnatal day 15, the group D15 was weaned and, on postnatal day 30 (natural weaning), the group D30 was weaned. The rats weaned on postnatal day 15, and administered subcutaneous Naltrexone (3 mg/kg) were from group D15 + NTX. Those weaned at 15 days of age exhibited higher depressive-like behavior, lesser reactivity time to sucrose, and higher intake of palatable food than the control group. The Naltrexone administration was observed to reverse some outcomes, such as increasing the reactivity time to sucrose and decreasing the quantity of palatable food consumed, to levels similar to those of the control group. Together, the findings of the present study are indicative of the vital role played by the opioidergic system in inducing the changes noted in the eating behavior patterns during adulthood, post early weaning.

Modulatory role of serotonin on feeding behavior.

The appearance, the odor, and the flavor of foods, all send messages to the encephalic area of the brain. The hypothalamus, in particular, plays a key role in the mechanisms that control the feeding behavior. These signals modulate the expression and the action of anorexigenic or orexigenic substances that influence feeding behavior. The serotonergic system of neurotransmission consists of neurons that produce and liberate serotonin as well as the serotonin-specific receptor. It has been proven that some serotonergic drugs are effective in modulating the mechanisms of control of feeding behavior. Obesity and its associated illnesses have become significant public health problems. Some drugs that manipulate the serotonergic systems have been demonstrated to be effective interventions in the treatment of obesity. The complex interplay between serotonin and its receptors, and the resultant effects on feeding behavior have become of great interest in the scientific community.

Early weaning disrupts feeding patterns in female juvenile rats through 5HT-system modulations.

Convergent evidence in literature shows that rapid disruption of maternal care and breastfeeding due to an early weaning protocol changes the development of several neurobehavioral patterns in rodents, including the circadian pattern of feeding. The serotoninergic system has been associated with the control of feeding patterns. Therefore, we aim to evaluate the patterns of feeding, the mRNA expression of 5 H T-1b, 5 H T-2c, and SERT on the hypothalamus, brainstem, and the body weight of female juvenile Wistar rats, submitted to early (PND15) or regular (PND30) weaning. The results demonstrate that early weaning promotes an increase in food intake in a 24 -h period, in the dark phase of the circadian cycle and in the four-hour time intervals at the beginning of the dark and light phases. Also, early weaning decreases the mRNA expression of 5 H T-1b, 5 H T-2c, and SERT on the hypothalamus, but increases it on the brainstem. Additionally, early weaning promotes an increase in body weight. Therefore, the present data demonstrate that early weaning changes the patterns of feeding in juvenile female rats and suggests that this behavioral modification is due to the modulations promoted in the 5 H T-system.

Early life stress induced by maternal separation during lactation alters the eating behavior and serotonin system in middle-aged rat female offspring.

Stressful events occurring during early life have been related to behavioral and neurochemical disturbances. Maternal separation during the first two weeks of life is a traumatic event that strongly affects the feeding behavior and serotonergic system of the progeny in adulthood. As this system modulates the feeding behavior, the present study aimed at investigating the effects of maternal separation-induced stress on both the feeding behavior and serotonergic system of the middle-aged female rats by manipulating this system using fluoxetine, a selective serotonin transporter inhibitor. Lactating Wistar rats were separated from their litters from postnatal day 2 (PND 2) to PND 14 for 3 h in the dark phase of the circadian cycle. The maternally separated (MS) and control (C) groups were distinguished from each other based on the incidence or absence of maternal separation (early life stress). All the analyses were done on the female offspring from one-year of age. Maternal separation anticipated the satiety point in these females. This anticipation was linked to lower food intake, meal duration and meal size. These results mirrored the effects of fluoxetine in the control animals. Furthermore, maternal separation was associated with 5ht1b serotonin receptor hyperexpression in the hypothalamus. These findings demonstrate that maternal separation has long-lasting effects on the eating behavior and serotonergic system and that this system could be responsible for mediating these behavioral outcomes.

Early weaning leads to disruption of homeostatic and hedonic eating behaviors and modulates serotonin (5HT) and dopamine (DA) systems in male adult rats.

Early weaning is associated with disruption of eating behavior. However, little is known about the mechanisms behind it. 5HT and DA systems are key regulators of homeostatic and hedonic eating behaviors, respectively. Thus, this study aims to evaluate the effects of early weaning on feeding behavior and 5HT and DA systems. For this, rats were submitted to regular (PND30) or early weaning (PND15) and between PND250 and PND300 were evaluated food intake of standard diet in response to 4 h food deprivation, during the 24 h period and per phase of the circadian cycle, in addition to the palatable food intake. Additionally, body mass and mRNA expression of 5HT1B, 5HT2C, SERT, DRD1 and DRD2 were evaluated in the hypothalamus and brainstem. The results demonstrate that early weaning promoted an increase in standard food intake in response to a 4 h food deprivation in the 24 h period and in the dark phase of the circadian cycle, in addition to an increased palatable food intake. No differences in body mass between regular or early weaning were observed. In the hypothalamus, increased mRNA expression of SERT and DRD1 was observed, but decreased 5HT1B mRNA expression. In the brainstem, the expression of 5HT1B, SERT, 5HT2C, DRD1 and DRD2 was increased in early weaned rats. In a nutshell, the stress promoted by early weaning has programmed the animals to be hyperphagic and to increase their palatable food intake, which was associated with modulation of 5HT and DA systems.

Dual exposure to stress in different stages of development affects eating behavior of male Wistar rats.

Maternal separation stress is a model of early life stress performed by the separation between dam and pups in the first days of life. The consequences of this early stress have been demonstrated on various behaviors, including feeding behavior. The results, however, are still controversial and it seems that a second exposure to stress later in life exacerbates the adverse outcomes. The present study aimed to determine the effects of maternal separation as a model of stress in early life, with or without a later life stress experience on eating behavior. Lactating Wistar rats were separated from their litters from postnatal day 2 (PND 2) to PND 14 for 3 h in the dark phase of the circadian cycle. The groups control (C) and separated (S) were composed. The assessment of food intake was performed between the ages of 60 and 150 days of life with a group that experienced only the early stress by maternal separation and with a second group that experienced the pre-weaning maternal separation stress and the food stress from 60 days of age. This food stress consisted of allowing visual and olfactory exposure of the animals to palatable food but did not allow the feeding. Maternal separation promoted higher palatable food and lower standard diet intake only after a double exposure to stress. Besides, the double exposure to stress promoted weight loss and an anxiety-like behavior. These outcomes were associated with a resistance to the anorectic effects of fluoxetine suggesting an alteration of the serotonergic system. Together, these findings indicate that maternal separation stress has long-lasting consequences on eating behavior, and that the dual exposure to stress seems more harmful to eating behavior outcomes. In addition, the results suggest that the serotonergic system is one candidate as the system mediating these alterations.

Early weaning modulates eating behavior and promotes hypofunction of the serotonergic (5HT) system in juvenile male rats.

Early life stress (ELS) has been associated with developmental impairments. Early weaning (EW) is a postnatal stress model consisting of interruption of lactation and maternal care. The 5HT-system has been associated with neurobehavioral modulations promoted by ELS. Thus, the present work aims to investigate the effects of early weaning on feeding behavior and serotonergic system of juvenile male rats. For this, rats were submitted to early (PND15) or natural (PND30) weaning and had the body weight, food intake in circadian phases, and food intake in response to fenfluramine assessed. mRNA expression of serotoninergic receptors (5HT1A and 5HT2C) and transporter (SERT) was assessed in the hypothalamus and brainstem, as well as NPY and POMC mRNA expression in hypothalamus. The results show that early weaning promoted changes in the percentage of weight gain during lactation period and increase in body weight at PND40. It was also observed that EW promoted increase and decrease in food intake in light and dark phase, respectively, and leads to a decreased action of fenfluramine on inhibition of food intake. In addition, early weaning promoted increased NPY and SERT mRNA expression in the hypothalamus and 5HT2C in the brainstem. Together, the data indicate that the stress caused by early weaning impairs the eating behavior of juvenile male rats through hypofunction of the 5HT-system.

Can physical exercise during gestation attenuate the effects of a maternal perinatal low-protein diet on oxygen consumption in rats?

A protocol of physical exercise, based on maximal oxygen uptake ((.)V(O2max)), for female rats before and during pregnancy was developed to evaluate the impact of a low-protein diet on oxygen consumption during gestation and growth rate of the offspring. Virgin female Wistar rats were divided into four groups as follows: untrained (NT, n =5); trained (T, n =5); untrained with low-protein diet (NT+LP, n =5); and trained with low-protein diet (T+LP, n =5). Trained rats were submitted to a protocol ofmoderate physical training on a treadmill over a period of 4 weeks (5 days week(-1) and 60 min day(-1), at 65% of (.)V(O2max)). At confirmation of pregnancy, the intensity and duration of the exercise was reduced. Low-protein groups received an 8% casein diet, and their peers received a 17% casein diet. The birthweight and growth rate of the pups up to the 90th day were recorded. Oxygen consumption ((.)V(O2)), CO2 production and respiratory exchange ratio (RER) were determined using an indirect open-circuit calorimeter. Exercise training increased (.)V(O2max) by about 20% when compared with the initial values (45.6+/-1.0 ml kg(-1) min(-1)). During gestation, all groups showed a progressive reduction in the resting (.)V(O2) values. Dams in the NT+LP group showed lower values of resting (.)V(O2) than those in the NT group. The growth rate of pups from low-protein-fed mothers was around 50% lower than that of their respective controls. The T group showed an increase in body weight from the 60th day onwards, while the NT+LP group presented a reduced body weight from weaning onwards. In conclusion, physical training attenuated the impact of the low-protein diet on oxygen consumption during gestation and on the growth rate of the offspring.