How are overweight and obesity associated with reinforcement learning deficits? A systematic review.

Reinforcement learning (RL) refers to the ability to learn stimulus-response or response-outcome associations relevant to the acquisition of behavioral repertoire and adaptation to the environment. Research data from correlational and case-control studies have shown that obesity is associated with impairments in RL. The aim of the present study was to systematically review how obesity and overweight are associated with RL performance.

Relationship between insulin and Netrin-1/DCC guidance cue pathway regulation in the prefrontal cortex of rodents exposed to prenatal dietary restriction.

Fetal restriction (FR) alters insulin sensitivity, but it is unknown how the metabolic profile associated with restriction affects development of the dopamine (DA) system and DA-related behaviors. The Netrin-1/DCC guidance cue system participates in maturation of the mesocorticolimbic DA circuitry. Therefore, our objective was to identify if FR modifies Netrin-1/DCC receptor protein expression in the prefrontal cortex (PFC) at birth and mRNA in adulthood in rodent males.

New Research Perspectives on the Interplay Between Genes and Environment on Executive Function Development.

Executive functions (EFs) are a set of skills responsible for the cognitive control of emotional states and behavior as well as for information processing required for learning and memory. Impairments in these abilities, such as focused attention, working memory, cognitive flexibility, and self-regulation, are implicated in a variety of psychopathologies across the lifespan. EF development shows a protracted course that begins in early childhood and continues throughout adolescence and into early adulthood.

Neonatal hypoxia-ischemia induces dysregulated feeding patterns and ethanol consumption that are alleviated by methylphenidate administration in rats.

Impulsivity, as observed in patients diagnosed with Attention-deficit/hyperactivity disorder (ADHD), can induce dysregulated behaviors such as binge eating and drug addiction. We previously demonstrated that neonatal hypoxia-ischemia (HI) resulted in ADHD-like behaviors in rats and that methylphenidate (MPH) administration (the first therapeutic option for ADHD) reversed these deficits. Here, we aimed at investigating addictive-like behaviors, such as the reward-based feeding behavior (using the BioDAQ monitor) and ethanol consumption (using the IA2BC procedure) in adult animals subjected to neonatal HI and treated with or without MPH.

Diminished insulin sensitivity is associated with altered brain activation to food cues and with risk for obesity - Implications for individuals born small for gestational age.

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents.

High gestational folic acid supplementation prevents hypoxia-ischemia-induced caspase-3 augmenting without changing synapsin and H3 methylation levels in the rat hippocampus.

Perinatal asphyxia is a peripartum event that can cause permanent sequelae to the newborns, affecting the brain development. Recently, it has been demonstrated that epigenetics mechanisms play an important role in this injury and that folic acid (FA) supplementation during pregnancy can affect these epigenetics modifications as well as gene expression. We have identified both positive and negative effects of FA treatment in rats submitted to a model of neonatal hypoxia-ischemia (HI).

Acrobatic exercise recovers object recognition memory impairment in hypoxic-ischemic rats.

Neonatal hypoxia-ischemia (HI) can lead to cognitive impairments and motor dysfunction. Acrobatic exercises (AE) were proposing as therapeutic option to manage HI motor deficits, however, the cognitive effects after this treatment are still poorly understood. Therefore, we evaluated the effects of AE protocol on memory impairments and brain plasticity markers after Rice-Vannucci HI rodent model.

Methylphenidate treatment increases hippocampal BDNF levels but does not improve memory deficits in hypoxic-ischemic rats.

Background: Methylphenidate (MPH) is a stimulant drug mainly prescribed to treat cognitive impairments in attention-deficit/hyperactivity disorder (ADHD). We demonstrated that neonatal hypoxia-ischemia (HI) induced attentional deficits in rats and MPH administration reversed these deficits. However, MPH effects on memory deficits after the HI procedure have not been evaluated yet.

Genetically predicted gene expression of prefrontal DRD4 gene and the differential susceptibility to childhood emotional eating in response to positive environment.

Genetic differential susceptibility states that individuals may vary both by exhibiting poor responses when exposed to adverse environments, and disproportionally benefiting from positive settings. The dopamine D4 receptor gene (DRD4) may be particularly implicated in these effects, including disturbed eating behaviors that might lead to obesity. Here, we explore differential susceptibility to positive environments according to the predicted genetically regulated gene expression of prefrontal cortex DRD4 gene.

Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children.

Background: Genetic polymorphisms of the dopamine transporter gene (DAT1) and perinatal complications associated with poor oxygenation are risk factors for attentional problems in childhood and may show interactive effects.

Methods: We created a novel expression-based polygenic risk score (ePRS) reflecting variations in the function of the DAT1 gene network (ePRS-DAT1) in the prefrontal cortex and explored the effects of its interaction with perinatal hypoxic-ischemic-associated conditions on cognitive flexibility and brain gray matter density in healthy children from two birth cohorts-MAVAN from Canada (n = 139 boys and girls) and GUSTO from Singapore (n = 312 boys and girls).

Results: A history of exposure to several perinatal hypoxic-ischemic-associated conditions was associated with impaired cognitive flexibility only in the high-ePRS group, suggesting that variation in the prefrontal cortex expression of genes involved in dopamine reuptake is associated with differences in this behavior.

Intrauterine growth restriction increases impulsive behavior and is associated with altered dopamine transmission in both medial prefrontal and orbitofrontal cortex in female rats.

Recent studies have implicated a role for impulsivity in the altered eating behaviors and the increased risk for obesity consistently associated with intrauterine growth restriction (IUGR). Changes in dopamine transmission within prefrontal areas are believed to contribute to these adverse outcomes. Here we investigated the impulsive behavior toward a delayed reward and evaluated dopamine levels and its receptors in the medial prefrontal (mPFC) and orbitofrontal (OFC) cortex of female adult rats exposed to IUGR.

Methylphenidate administration reverts attentional inflexibility in adolescent rats submitted to a model of neonatal hypoxia-ischemia: Predictive validity for ADHD study.

Perinatal complications such as birth asphyxia were associated with a higher risk for Attention-Deficit/Hyperactivity Disorder (ADHD) in humans. Data from a rat model of neonatal hypoxia-ischemia (HI) have revealed inattention, impulsive behavior and dopamine (DA) disturbances in the prefrontal cortex (PFC), confirming the face validity and construct validity for ADHD study. However, the predictive validity (similar therapeutic efficacy of the pharmacological treatment available in the clinic) should be considered.

Early environmental influences on the development of children's brain structure and function.

The developing brain in utero and during the first years of life is highly vulnerable to environmental influences. Experiences occurring during this period permanently modify brain structure and function through epigenetic modifications (alterations of the DNA structure and chromatin function) and consequently affect the susceptibility to mental disorders. In this review, we describe evidence linking adverse environmental variation during early life (from the fetal period to childhood) and long-term changes in brain volume, microstructure, and connectivity, especially in amygdala and hippocampal regions.

Neonatal hypoxia-ischemia caused mild motor dysfunction, recovered by acrobatic training, without affecting morphological structures involved in motor control in rats.

The aim of this study was to evaluated motor function and morphological aspects of the components involved in motor control (sensorimotor cortex, spinal cord, sciatic nerve, neuromuscular junctions and skeletal muscle) in male Wistar rats exposed to a model of neonatal hypoxic-ischemic encephalopathy (HIE) and the possible influence of different physical exercise protocols - treadmill and acrobatic. Male Wistar rats at the 7 post-natal day (PND) were submitted to the HIE model and from the 22 until 60 PND the exercise protocols (treadmill or acrobatic training) were running. After the training, the animals were evaluated in Open Field, Ladder Rung Walking and Rotarod tasks and after samples of the motor control components were collected.

Gestational folic acid supplementation does not affects the maternal behavior and the early development of rats submitted to neonatal hypoxia-ischemia but the high supplementation impairs the dam's memory and the Na, K - ATPase activity in the pup's hippocampus.

Folic acid (FA) is a B-complex vitamin important to the development of the fetus, being supplemented during pregnancy. Our recent findings showed that gestation supplementation (normal and excess doses) prevented the cognitive deficits and BDNF imbalance in adult rats that were submitted to neonatal hypoxia-ischemia (HI). To better understand this protective effect, the present study aimed to evaluate whether FA supplementation could be related to (1) maternal behavior, memory and Na, K - ATPase activity in the hippocampus of the dams; (2) on somatic growth, early neurobehavioral development and Na, K - ATPase activity in the hippocampus of the offspring; and (3) the effects of this supplementation in pups submitted to neonatal HI.

Folic acid supplementation during pregnancy prevents cognitive impairments and BDNF imbalance in the hippocampus of the offspring after neonatal hypoxia-ischemia.

Folic acid (FA) supplementation (400 μg/day) has been recommended during pregnancy to prevent neural tube defects. However, in some countries, flours are required to be fortified with FA, possibly increasing the levels of this vitamin in pregnant women. Our previous studies have evidenced a dual effect of the FA treatment in a rat model of neonatal hypoxia-ischemia (HI).

Prefrontal cortex dysfunction in hypoxic-ischaemic encephalopathy contributes to executive function impairments in rats: Potential contribution for attention-deficit/hyperactivity disorder.

Objectives: The attention-deficit/hyperactivity disorder (ADHD) compromises the quality of life of individuals including adaptation to the social environment. ADHD aetiology includes perinatal conditions such as hypoxic-ischaemic events; preclinical studies have demonstrated attentional deficits and impulsive-hyperactive outcomes after neonatal hypoxic and/or ischaemic intervention, but data are missing to understand this relationship. Thus, the aim of this study was to evaluate executive function (EF) and impulsivity, and tissue integrity and dopaminergic function in the prefrontal cortex (PFC) of rats submitted to hypoxia-ischaemia (HI).

Environmental enrichment attenuates the blood brain barrier dysfunction induced by the neonatal hypoxia-ischemia.

Environmental enrichment (EE) is considered an efficient neuroprotector against neonatal hypoxia-ischemia (HI). Nevertheless, the mechanisms involved are not yet clear. In this context, the aim of this study was to investigate the effects of neonatal HI and environmental stimulation in the hippocampus of rats at 3 different time points (PND 8, 22 and 60), evaluating some aspects of BBB structure and function.

Behavioral benefits of maternal swimming are counteracted by neonatal hypoxia-ischemia in the offspring.

Hypoxia-ischemia (HI) represents one of the most common causes of neonatal encephalopathy. The central nervous system injury comprises several mechanisms, including inflammatory, excitotoxicity, and redox homeostasis unbalance leading to cell death and cognitive impairment. Exercise during pregnancy is a potential therapeutic tool due to benefits offered to mother and fetus.

Folic Acid Can Contribute to Memory Deficit and Na+, K+- ATPase Failure in the Hippocampus of Adolescent Rats Submitted to Hypoxia- Ischemia.

Recent findings have demonstrated a dual effect of the folic acid (FA) supplementation on the nervous system of rats. We found that FA treatment prevented memory impairment and Na(+), K(+)- ATPase inhibition in the striatum and cortex in adult rats that suffered neonatal hypoxia-ischemia (HI). However, spatial memory deficit has been associated with FA supplementation.

Effect of maternal exercise on biochemical parameters in rats submitted to neonatal hypoxia-ischemia.

Pregnancy is a critical period for brain metabolic programming, being affected by individual environment, such as nutrition, stress, and physical exercise. In this context, we previously reported a cerebral antioxidant upregulation and mitochondrial biogenesis in the offspring delivered from exercised mothers, which could provide neuroprotection against neonatal insults. Hypoxia-ischemia (HI) encephalopathy is one of the most studied models of neonatal brain injury; disrupting motor, cognitive, and learning abilities.

Neonatal hypoxia-ischemia induces attention-deficit hyperactivity disorder-like behavior in rats.

Attention-deficit hyperactivity disorder (ADHD) may be caused by genetic or environmental factors. Among environmental factors, perinatal complications are related, such as neonatal hypoxia-ischemia (HI). Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats, and to correlate the behavioral results with brain damage volume.

Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile.

Effects of daily environmental enrichment on behavior and dendritic spine density in hippocampus following neonatal hypoxia-ischemia in the rat.

Hypoxia-ischemia (HI) is the main cause of mortality in the perinatal period and morbidity, in survivors, which is characterized by neurological disabilities. The immature brain is highly susceptible to hypoxic-ischemic insult and is responsive to environmental stimuli, such as environmental enrichment (EE). Previous results indicate that EE recovered memory deficits in adult rats without reversing hippocampal atrophy related to HI.