scholarly journals Multi-tissue Multi-omics Nutrigenomics Indicates Context-specific Effects of DHA on Rat Brain

2020 ◽  
Author(s):  
Guanglin Zhang ◽  
Qingying Meng ◽  
Montgomery Blencowe ◽  
Agrawal Rahul ◽  
Fernando Gomez-Pinilla ◽  
...  
Keyword(s):  
Serum Triglyceride ◽  
Chow Group ◽  
Chow Diet ◽  
Immune Functions ◽  
Specific Effects ◽  
High Fructose ◽  
Metabolic Conditions ◽  
Nutritional Effects ◽  
Context Specific ◽  
The Brain

AbstractScopeWe explored the influence of DHA on cardiometabolic and cognitive phenotypes, and multiomic alterations in the brain under two metabolic conditions to understand context-specific nutritional effects.Methods and ResultsRats were randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduced serum triglyceride and improved insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affected genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA altered immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling revealed context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus.ConclusionDHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.

Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

2019 ◽  
Vol 25 (23) ◽  
pp. 2555-2568 ◽  
Author(s):  
Rajeev Taliyan ◽  
Sarathlal K. Chandran ◽  
Violina Kakoty
Keyword(s):  
Diabetes Mellitus ◽  
Protein Trafficking ◽  
Metabolic Stress ◽  
Insulin Receptors ◽  
Metabolic Dysfunction ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Endocrine Hormone ◽  
Metabolic Conditions ◽  
The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

scholarly journals Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaona Acharjee ◽  
Paul M. K. Gordon ◽  
Benjamin H. Lee ◽  
Justin Read ◽  
Matthew L. Workentine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Expression Patterns ◽  
Immune Functions ◽  
Autoimmune Encephalomyelitis ◽  
Transcriptional Changes ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Experimental Autoimmune

AbstractMicroglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.

ERP Evidence for Implicit Priming of Top–Down Control of Attention

2016 ◽  
Vol 28 (5) ◽  
pp. 763-772 ◽  
Author(s):  
Chris Blais ◽  
Emily Hubbard ◽  
George R. Mangun
Keyword(s):  
Associative Learning ◽  
Stroop Effect ◽  
Congruency Effect ◽  
Simon Task ◽  
Electrical Signal ◽  
Lower Visual Field ◽  
Specific Effects ◽  
High Conflict ◽  
Contemporary Work ◽  
Context Specific

Proportion congruency effects are the observation that the magnitude of the Stroop effect increases as the proportion of congruent trials in a block increases. Contemporary work shows that proportion effects can be specific to a particular context. For example, in a Simon task in which items appearing above fixation are mostly congruent and items appearing below fixation are mostly incongruent, the Simon effect is larger for the items appearing at the top. There is disagreement as to whether these context-specific effects result from simple associative learning or, instead, a type of conflict-mediated associative learning. Here, we address this question in an ERP study using a Simon task in which the proportion congruency effect was context-specific, manipulating the proportion of congruent trials based on location (upper vs. lower visual field). We found significant behavioral proportion congruency effects that varied with the specific contexts. In addition, we observed that the N2 response of the ERPs to the stimuli was larger in amplitude for the high congruent (high conflict) versus low congruent (low conflict) conditions/contexts. Because the N2 is known to be greater in amplitude also for trials where conflict is high and is believed to be an electrical signal related to conflict detection in the medial frontal cortex, this supports the idea that conflict-mediated associative learning is involved in the proportion congruency effect.

Leptin Functioning in Eating Disorders

CNS Spectrums ◽  
2004 ◽  
Vol 9 (7) ◽  
pp. 523-529 ◽  
Author(s):  
Palmiero Monteleone ◽  
Antonio DiLieto ◽  
Eloisa Castaldo ◽  
Mario Maj
Keyword(s):  
Physical Activity ◽  
Eating Disorders ◽  
Body Weight ◽  
Eating Behaviors ◽  
Clinical Manifestations ◽  
Immune Functions ◽  
Abnormal Eating ◽  
The Brain

AbstractLeptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.

scholarly journals Context-specific Effects of Fibulin-5 (DANCE/EVEC) on Cell Proliferation, Motility, and Invasion

2002 ◽  
Vol 277 (30) ◽  
pp. 27367-27377 ◽  
Author(s):  
William P. Schiemann ◽  
Gerard C. Blobe ◽  
Dario E. Kalume ◽  
Akhilesh Pandey ◽  
Harvey F. Lodish
Keyword(s):  
Cell Proliferation ◽  
Specific Effects ◽  
Context Specific

Abstract 010: The Role of Angiotensin AT 1A Receptors in Leptin-sensitive Cells in Resting Metabolic Rate Control

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Kristin E Claflin ◽  
Justin L Grobe
Keyword(s):  
Metabolic Rate ◽  
Rate Control ◽  
Leptin Receptor ◽  
Resting Metabolic Rate ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
Chow Diet ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis ◽  
The Brain

The brain renin-angiotensin system (RAS) and leptin contribute to the control of resting metabolic rate (RMR) and their receptors are co-expressed in areas of the brain critical for metabolic control; thus angiotensin and leptin may interact within the brain to regulate RMR and obesity. Inhibition of the brain RAS attenuates sympathetic nerve activity (SNA) responses to leptin, leading us to hypothesize that the brain RAS mediates the RMR effects of leptin. Mice lacking angiotensin AT 1A receptors in leptin receptor-expressing cells (ObRb-Cre x AT 1A flox/flox ; “KO”) exhibited normal body weight (15 weeks of age: control n=28, 26.0 ± 0.7, vs KO n=35, 25.8 ± 0.6 g), food intake (control n=12, 3.1 ± 0.15, vs KO n=15, 3.4 ± 0.14 g) and RMR (control n=13, 0.15 ± 0.004, vs KO n=15, 0.16 ± 0.006 kcal/hr) on standard chow diet. Brown adipose SNA responses to acute leptin injection, however, were completely attenuated in KO mice. When maintained on a 45% high fat diet (HFD), KO mice gained significantly more fat mass (control n=35, 5.6 ± 0.4, vs KO n=31, 7.4 ± 0.5 g, P<0.05) and body mass (control, 27.4 ± 0.6, vs KO, 29.6 ± 0.6 g, P<0.05) due to a loss of diet-induced thermogenesis (control n=22, 0.18 ± 0.008, vs. KO n=12, 0.16 ± 0.004 kcal/hr, P<0.05). KO mice exhibited attenuated hypothalamic proopiomelanocortin (POMC) gene expression and partially attenuated RMR responses to alpha-melanocyte stimulating hormone (αMSH; control n=3, 0.25 ± 0.01, vs KO n=7, 0.2 ± 0.01 kcal/hr, P<0.05) indicating that the interaction between leptin and AT 1A modulates both αMSH production and action. To localize the site of the brain RAS-leptin interaction, we developed novel multi-transgenic mouse models which expresses GFP via the AT 1A promoter (NZ44, from GenSat) and/or conditional activation of a tdTomato reporter (ROSA-stop flox -tdTomato) in cells expressing the leptin receptor (ObRb-Cre) or agouti-related peptide (AgRP-Cre). Immunohistochemical staining of adrenocorticotropin in brain tissue from NZ44 mice revealed no localization of AT 1A to POMC neurons; in contrast, AT 1A was strongly localized with AgRP promoter activity. Taken together, these data support a critical role for angiotensin AT 1A receptors on AgRP neurons in the arcuate nucleus in resting metabolic rate control.

scholarly journals Ketohexokinase knockout mice, a model for essential fructosuria, exhibit altered fructose metabolism and are protected from diet-induced metabolic defects

2018 ◽  
Vol 315 (3) ◽  
pp. E386-E393 ◽  
Author(s):  
Corin O. Miller ◽  
Xiaodong Yang ◽  
Ku Lu ◽  
Jin Cao ◽  
Kithsiri Herath ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
De Novo ◽  
Liver Weight ◽  
De Novo Lipogenesis ◽  
Chow Diet ◽  
Fructose Metabolism ◽  
Metabolic Defects ◽  
Glucose And Lipid Metabolism ◽  
High Fructose ◽  
Altered Glucose

Fructose consumption in humans and animals has been linked to enhanced de novo lipogenesis, dyslipidemia, and insulin resistance. Hereditary deficiency of ketohexokinase (KHK), the first enzymatic step in fructose metabolism, leads to essential fructosuria in humans, characterized by elevated levels of blood and urinary fructose following fructose ingestion but is otherwise clinically benign. To address whether KHK deficiency is associated with altered glucose and lipid metabolism, a Khk knockout (KO) mouse line was generated and characterized. NMR spectroscopic analysis of plasma following ingestion of [6-13C] fructose revealed striking differences in biomarkers of fructose metabolism. Significantly elevated urine and plasma 13C-fructose levels were observed in Khk KO vs. wild-type (WT) control mice, as was reduced conversion of 13C-fructose into plasma 13C-glucose and 13C-lactate. In addition, the observation of significant levels of fructose-6-phosphate in skeletal muscle tissue of Khk KO, but not WT, mice suggests a potential mechanism, whereby fructose is metabolized via muscle hexokinase in the absence of KHK. Khk KO mice on a standard chow diet displayed no metabolic abnormalities with respect to ambient glucose, glucose tolerance, body weight, food intake, and circulating trigylcerides, β-hydroxybutyrate, and lactate. When placed on a high-fat and high-fructose (HF/HFruc) diet, Khk KO mice had markedly reduced liver weight, triglyceride levels, and insulin levels. Together, these results suggest that Khk KO mice may serve as a good model for essential fructosuria in humans and that inhibition of KHK offers the potential to protect from diet-induced hepatic steatosis and insulin resistance.

scholarly journals Using Transcriptomic Hidden Variables to Infer Context-Specific Genotype Effects in the Brain

2019 ◽  
Vol 105 (3) ◽  
pp. 562-572
Author(s):  
Bernard Ng ◽  
William Casazza ◽  
Ellis Patrick ◽  
Shinya Tasaki ◽  
Gherman Novakovsky ◽  
...  
Keyword(s):  
Hidden Variables ◽  
Context Specific ◽  
The Brain ◽  
Genotype Effects

scholarly journals Context-specific effects of facial dominance and trustworthiness on hypothetical leadership decisions

PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0214261
Author(s):  
Hannah S. Ferguson ◽  
Anya Owen ◽  
Amanda C. Hahn ◽  
Jaimie Torrance ◽  
Lisa M. DeBruine ◽  
...  
Keyword(s):  
Specific Effects ◽  
Context Specific ◽  
Leadership Decisions

scholarly journals Age-Associated Changes in the Immune System and Blood–Brain Barrier Functions

2019 ◽  
Vol 20 (7) ◽  
pp. 1632 ◽  
Author(s):  
Michelle Erickson ◽  
William Banks
Keyword(s):  
Central Nervous System ◽  
Immune System ◽  
Blood Brain Barrier ◽  
Neurological Disorders ◽  
Brain Barrier ◽  
Immune Functions ◽  
Blood Brain ◽  
The Brain ◽  
Brain Barriers

Age is associated with altered immune functions that may affect the brain. Brain barriers, including the blood–brain barrier (BBB) and blood–CSF barrier (BCSFB), are important interfaces for neuroimmune communication, and are affected by aging. In this review, we explore novel mechanisms by which the aging immune system alters central nervous system functions and neuroimmune responses, with a focus on brain barriers. Specific emphasis will be on recent works that have identified novel mechanisms by which BBB/BCSFB functions change with age, interactions of the BBB with age-associated immune factors, and contributions of the BBB to age-associated neurological disorders. Understanding how age alters BBB functions and responses to pathological insults could provide important insight on the role of the BBB in the progression of cognitive decline and neurodegenerative disease.

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