Search

Introduction: Adolescence is an important stage of maturation for various brain structures. It is during this time therefore that the brain may be more vulnerable to environmental factors such as diet that may influence mood and memory. Diets high in fat and sugar (termed a cafeteria diet) during adolescence have been shown to negatively impact upon cognitive performance, which may be reversed by switching to a standard diet during adulthood. Consumption of a cafeteria diet increases both peripheral and central levels of interleukin-1β (IL-1β), a pro-inflammatory cytokine which is also implicated in cognitive impairment during the ageing process. It is unknown whether adolescent exposure to a cafeteria diet potentiates the negative effects of IL-1β on cognitive function during adulthood. Methods: Male Sprague-Dawley rats consumed a cafeteria diet during adolescence after which time they received a lentivirus injection in the hippocampus to induce chronic low-grade overexpression of IL-1β. After viral integration, metabolic parameters, circulating and central pro-inflammatory cytokine levels, and cognitive behaviours were assessed. Results: Our data demonstrate that rats fed the cafeteria diet exhibit metabolic dysregulations in adulthood, which were concomitant with low-grade peripheral and central inflammation. Overexpression of hippocampal IL-1β in adulthood impaired spatial working memory. However, adolescent exposure to a cafeteria diet, combined with or without hippocampal IL-1β in adulthood did not induce any lasting cognitive deficits when the diet was replaced with a standard diet in adulthood. Discussion: These data demonstrate that cafeteria diet consumption during adolescence induces metabolic and inflammatory changes, but not behavioural changes in adulthood. [ABSTRACT FROM AUTHOR]

A high-fat diet (HFD) during pregnancy influences the neurodevelopment of progeny, particularly in the hippocampus, a brain region involved in cognitive processes. The hippocampus has high levels of leptin receptors (Ob-R) that participate in synaptic plasticity. This study examined the effect of maternal HFD during gestation on Ob-R expression in the CA1 and CA3 hippocampal regions, and its relationship with spatial learning and memory in the offspring. We used 48 rat pups: 24 from dams fed a balanced diet (BD, 6.2% fat) and 24 from those fed an HFD (42% fat) during pregnancy. We recorded weight gain and food intake in each pup every day beginning on postnatal day 3 (PND 3). Memory acquisition was assessed on PND 28 and memory retention on PND 42 in the Morris water maze (MWM). Then, 12 pups per group were selected randomly and subjected to bioimpedance spectroscopy. The remaining offspring was perfused to determine Ob-R expression levels in the CA1 and CA3 hippocampal regions. Interestingly, HFD pups had significantly higher weight gain, food intake, and fat mass than BD offspring. Interestingly, the HFD group showed poor memory performance, which correlated with changes in the Ob-R expression in both hippocampal regions. These data indicate that maternal exposure to HFD impacts neurodevelopmental and cognitive functions of the offspring. [ABSTRACT FROM AUTHOR]

Objectives: Creativity requires the ability to combine existing mental representations in new ways and depends, in part, on the hippocampus. Hippocampal function is, in turn, affected by a number of health factors, including aerobic fitness, excess adiposity, and diet. Specifically, in rodent studies, diets high in saturated fatty acids and sugar – hallmarks of a western diet– have been shown to negatively impact hippocampal function and thereby impair performance on cognitive tasks that require the hippocampus. Yet relatively few studies have examined the relationship between diet and hippocampal-dependent cognition in children. Methods: The current study therefore sought to explore the relationship of several diet quality markers including dietary lipids (saturated fatty acids and omega-3 fatty acids), simple carbohydrates (added sugars), and dietary fiber with creativity in preadolescent children. Participants (N = 57; mean age = 9.1 years) completed the Verbal Form of the Torrance Test of Creative Thinking (TTCT), a standardized test of creativity known to require the hippocampus. Additionally, participants completed a 3-day food intake record with the assistance of a parent, underwent dual energy x-ray absorptiometry (DXA) to assess central adiposity, and VO2max testing to assess aerobic fitness. Results: Added sugar intake was negatively associated, and dietary fiber was positively associated with overall TTCT performance. These relationships were sustained even after controlling for key covariates. Discussion: These findings are among the first to report an association between added sugar consumption and hippocampal-dependent cognition during childhood and, given the key role of the hippocampus in learning and memory, as well as creative thinking, have potential educational and public health implications. [ABSTRACT FROM AUTHOR]

Objective: Research demonstrates a link between diet-induced obesity and cognitive impairments; however, no studies have utilized the Sholl analysis to assess changes in dendritic arborization as a possible cause of obesity-induced memory deficits. Therefore, the purpose of this study was to examine the effect of a Western-style diet (WSD) on memory and dendritic complexity of male Sprague-Dawley rats. Methods: Male Sprague-Dawley rats (n = 18) were fed either a control or WSD. Spatial memory and episodic memory were assessed using the Morris Water Maze and novel object recognition (NOR) tasks, respectively. At termination, brains were removed and prepared with the Golgi-Cox method. Stained neurons in both the hippocampus and entorhinal cortex (EC) were imaged and digitally reconstructed. Results: Results indicated significant differences in percent body fat and TNFα levels between dietary conditions. WSD males also experienced reduced NOR exploration ratios, but no deficits in spatial memory were observed. Analysis of dendritic length and number of branch points revealed no significant differences in either the EC or the hippocampus; however, the Sholl analysis indicated that a WSD increased neuronal complexity in the EC. Discussion: Sholl analysis of the EC suggests a possible diet-induced dysfunction of pruning, which may contribute to reduced performance on the NOR task. Elevated TNFα levels indicate a putative role of inflammation in neuronal remodeling. The results demonstrate the importance of investigating mechanisms underlying obesity-related cognitive impairments. [ABSTRACT FROM AUTHOR]

Objectives: Added dietary sugars contribute substantially to the diet of children and adolescents in the USA, and recent evidence suggests that consuming sugar-sweetened beverages (SSBs) during early life has deleterious effects on hippocampal-dependent memory function. Here, we test whether the effects of early-life sugar consumption on hippocampal function persist into adulthood when access to sugar is restricted to the juvenile/adolescent phase of development. Methods: Male rats were given ad libitum access to an 11% weight-by-volume sugar solution (made with high fructose corn syrup-55) throughout the adolescent phase of development (post-natal day (PN) 26-56). The control group received a second bottle of water instead, and both groups received ad libitum standard laboratory chow and water access throughout the study. At PN 56 sugar solutions were removed and at PN 175 rats were subjected to behavioral testing for hippocampal-dependent episodic contextual memory in the novel object in context (NOIC) task, for anxiety-like behavior in the Zero maze, and were given an intraperitoneal glucose tolerance test. Results: Early-life exposure to SSBs conferred long-lasting impairments in hippocampal-dependent memory function later in life- yet had no effect on body weight, anxiety-like behavior, or glucose tolerance. A second experiment demonstrated that NOIC performance was impaired at PN 175 even when SSB access was limited to 2 hours daily from PN 26-56. Discussion: Our data suggest that even modest SSB consumption throughout early life may have long-term negative consequences on memory function during adulthood. [ABSTRACT FROM AUTHOR]

Lifestyle behaviours, such as eating and physical activity (PA), have been recognised as factors that may influence age-related cognitive decline. A high-fat diet and sedentary behaviour have been associated with poor cognitive performance in a variety of domains, in both animals and humans, while caloric restriction (CR) and PA are typically associated with positive outcomes. The lifestyle-associated changes in cognitive performance typically involve areas of the brain that are vulnerable to structural alterations, such as the hippocampus. Here, we frame age-related cognitive change in regard to the brain and cognitive reserve theories and discuss the potential for CR and PA interventions, independently and in combination, to affect cognitive trajectories. We provide mechanistic support for these interventions to affect cognitive performance through BDNF and its high-affinity receptor TrkB. Further, we offer suggestions for future study designs to investigate these relationships and urge researchers to be mindful of the potential mediating roles of BDNF and TrkB. [ABSTRACT FROM AUTHOR]

Successful coping with stressful events involves adaptive and cognitive processes in the brain that make the individual more resilient to similar stressors in the future. Stressful events result in the secretion of glucocorticoids (GCs) from the adrenal glands into the blood stream. Early work proved instrumental for developing the concept that these hormones act in the brain to coordinate physiological and behavioral responses to stress through binding to two different GC-binding receptors. Once activated these receptors translocate to the nucleus where they act on target genes to facilitate (or sometimes inhibit) transcription. There are two types of receptors in the brain, the mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). This review summarizes recent work which provides new insights regarding the genomic action of these receptors, both under baseline conditions and following exposure to acute stress. This work is discussed alongside the extensive studies undertaken in this field previously and new, and exciting “big data” studies which have generated a wealth of relevant data. The consequence of these new insights will challenge existing assumptions about the role of MRs and GRs and pave the way for the implementation of novel and improved methodologies to identify the role these corticosteroid receptors have in stress-related behavioral adaptation. [ABSTRACT FROM AUTHOR]

Objective: This study was carried out to understand the effects of zinc deficiency in rats aged 0~2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus. Methods: The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers. After 37 days, the zinc concentrations in the plasma and hippocampus were measured, and the behavioral function of the offspring rats was measured using the passive avoidance performance test. We then assessed the DNA methylation patterns of the exon IX of BDNF by methylation-specific quantitative real-time PCR and the mRNA expression of BDNF in the hippocampus by RT-PCR. Results: Compared with the ZA and PF groups, rats in the ZD group had shorter latency period, lower zinc concentrations in the plasma and hippocampus (P < 0.05). Interestingly, the DNA methylation of the BDNF exon IX was significantly increased in the ZD group, compared with the ZA and PF groups, whereas the expression of the BDNF mRNA was decreased. In addition, the DNMT1 mRNA expression was significantly upregulated and DNMT3A was downregulated in the ZD group, but not in the ZA and PF groups. Conclusion: The learning and memory damage in offspring may be a result of the epigenetic changes of the BDNF genes in response to the zinc-deficient diet during 0~2 month period. Furthermore, this work supports the speculative notion that altered DNA methylation of BDNF in the hippocampus is one of the main causes of cognitive impairment by zinc deficiency. [ABSTRACT FROM AUTHOR]

Objective: Excess glucocorticoid (GC) exposure on the fetal brain during critical stages of development has considerable effects on the development of the central nervous system (CNS). This study thus aimed to evaluate the differential effects of GC exposure on critical growth factor levels during different stages of brain maturation.Methods: For this purpose, forty-two rat pups were divided into six groups based on the timing of betamethasone administration. Rats in the treatment groups were exposed to intraperitoneal betamethasone injections beginning at different time points (postnatal days 1, 2, and 3). Rats in the placebo group received the same volume of 0.9% saline via the same fashion. Pups were sacrificed at 24 h following the final injection for determining the neuronal density and immunohistochemical evaluation of critical growth factors.Results: In the groups treated with betamethasone on postnatal day 1 (P1) and P2, which correspond to 22-24 and 24-28 gestational weeks in humans, the neuronal count in the hippocampal regions was significantly lower than their control groups. However, if steroid therapy was administered on P3, corresponding to 28-32 weeks in humans, no difference was observed between the two groups. Growth factors were affected in different ways depending on the steroid administration time and evaluated region.Conclusions: The results suggest that the modulating effect of steroids on neuron count and growth factor response depends on the stage of brain development at the time of exposure. Therefore, this may be one of the key determinants affecting the deleterious and beneficial effects of GCs on the CNS. [ABSTRACT FROM AUTHOR]

Objectives: Forced and voluntary exercises are known to improve cognition and induce neuroprotection after stroke, however, any effects of involuntary movement induced by functional electrical stimulation (FES) are unclear. The effects of involuntary exercise induced by FES, forced and voluntary exercise on the recovery of cognitive function in vascular dementia and the regional repair of ischaemic lesions were investigated using a rat model. Methods: Wistar rats were randomly assigned to a sham group, a vascular dementia control group (VD), an involuntary exercise group (I-Ex), a forced exercise group (F-Ex) or a voluntary exercise group (V-Ex). An object recognition test (ORT) and an object location test (OLT) were used to evaluate the recovery of cognitive function. Levels of synapsin I (SYN), synaptophysin (SYP), postsynaptic density 95 (PSD-95), microtubule-associated protein 2 (MAP-2) and Tau in the hippocampus were evaluated using western blotting and immunohistochemistry. Nissl staining was applied to visualise the loss of viable neurons from the hippocampus. Results: Involuntary exercise and voluntary exercise both improved cognition in terms of ORT and OLT results. Forced exercise only improved ORT results. The levels of SYN, PSD-95, MAP-2 and Tau in the hippocampus were enhanced by all three patterns of exercise training. Moreover, all three patterns reduced losses of dendrons and neurons in the hippocampal CA1 and CA2 zones, but without significant differences among the three exercise regimens. Conclusion: Involuntary exercise induced by FES has beneficial effects on cognitive function after vascular dementia comparable to those of forced and voluntary exercise. [ABSTRACT FROM AUTHOR]

Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5–7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomesin vitroand (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is a member of neurotrophins family that plays a pivotal role in memory and learning. Brain-derived neurotrophic factor mediates health benefits of physical activity both in humans and animals. The nerve damage and cognitive impairment in diabetic rats are thought to be the result of reduced BDNF levels. The purpose of this study was to examine the effect of short- and long-term moderate forced exercise on BDNF levels in the hippocampus of type 1 diabetic rats. Methods: A total of 40 male Wistar rats have been divided into four groups [control group, sedentary diabetic (SD) group, diabetic group with 2 week exercise, and diabetic group with 8 week exercise]. Exercised groups were treated with moderate treadmill running for 60 minutes per day on a rat treadmill. The animals were tested in a Morris water maze (MWM) for spatial memory and the BDNF levels in the hippocampus were assessed by ELISA kit. Results: The Spatial memory test showed a significant improvement in exercised groups in comparison to sedentary groups. Based on the running protocol no significant difference was found on BDNF levels between groups. Discussion: It was shown that spatial memory was improved by the exercise protocol, while the BDNF levels did not change significantly in any group. As a BDNF secretion in the brain is dependent on running paradigm factor, the protocol chosen might not be intensive or long enough to increase the BDNF levels. Exercise may improve spatial memory in type 1 diabetic rats in a way that BDNF is not included. [ABSTRACT FROM AUTHOR]

N-Methyl- d-aspartate receptor (NMDAR)-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. Here, using quantitative RT-PCR, we investigated the hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress paradigm that mimics clinically relevant conditions of simultaneously affected emotionality and hippocampus-dependent functions. A 2-week stress procedure, which comprised ethologically valid stressors, exposure to a rat and social defeat, was applied to male C57BL/6J mice. For predation stress, mice were introduced into transparent containers that were placed in a rat home cage during the night; social defeat was applied during the daytime using aggressive CD1 mice. This treatment impaired hippocampus-dependent performance during contextual fear conditioning. A correlation between this behavior and food displacement performance was demonstrated, suggesting that burrowing behavior is affected by the stress procedure and is hippocampus-dependent. Stressed mice ( n = 22) showed behavioral invigoration and anomalous anxiolytic-like profiles in the O-maze and brightly illuminated open field, unaltered short-term memory in the step-down avoidance task and enhanced aggressive traits, as compared to non-stressed mice ( n = 10). Stressed mice showed increased basal serum corticosterone concentrations, hippocampal mRNA expression for the NR2A subunit of the NMDAR and in the NR2A/NR2B ratio; mRNA expression of NR2B and NR1 was unchanged. Thus, stress-induced aberrations in both hippocampal-dependent performance and emotional abnormalities are associated with alterations in hippocampal mRNA NR2A levels and the NR2A/NR2B ratio and not with mRNA expression of NR2B or NR1. [ABSTRACT FROM AUTHOR]

Objectives. To review neuroimaging intermediate phenotypes of MDD and their relation to genetic risk variants. Methods. A systematic literature search of peer-reviewed English language articels using PubMed () was performed. Results. Comprehensive evidence on the influence of serotonergic genes ( SLC6A4, HTR1A, MAOA, TPH2) and BDNF on the following neural intermediate phenotypes is displayed: amygdala reactivity, coupling of amygdala-anterior cingulate cortex (ACC) activity, ACC volume, hippocampal volume and serotonin receptor 1A (5-HT1A) binding potential (BP). Conclusions. Intermediate phenotypes may bridge the gap between genotype and phenotype by reducing the impreciseness of psychiatric phenotypes and yield more insights into the underlying biology. [ABSTRACT FROM AUTHOR]