scholarly journals Peripheral Insulin Regulates a Broad Network of Gene Expression in the Hypothalamus, Hippocampus and Nucleus Accumbens

2021 ◽  
Author(s):  
Weikang Cai ◽  
Xuemei Zhang ◽  
Thiago M. Batista ◽  
Rubén García-Martín ◽  
Samir Softic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Cholesterol Biosynthesis ◽  
Peripheral Circulation ◽  
Fatty Acyl ◽  
Pentose Phosphate ◽  
Gaba A ◽  
Expression Of Genes ◽  
Pentose Phosphate Pathways ◽  
The Brain

The brain is now recognized as an insulin sensitive tissue, however, the role of changing insulin concentrations in the peripheral circulation on gene expression in the brain is largely unknown. Here we perform hyperinsulinemic-euglycemic clamp on 3-month-old male C57BL/6 mice for 3 hours. We show that increases in peripheral insulin within the physiological range regulate expression of a broad network of gene expression in the brain compared with saline-infused controls. Insulin regulates distinct pathways in the hypothalamus, hippocampus and nucleus accumbens. Insulin shows its most robust effect in the hypothalamus and regulates multiple genes involved in neurotransmission, including up-regulating expression of multiple subunits of GABA-A receptors, Na<sup>+</sup> and K<sup>+</sup> channels, and SNARE proteins; differentially modulating glutamate receptors; and suppressing multiple neuropeptides. Insulin also strongly modulates metabolic genes in the hypothalamus, suppressing genes in the glycolysis and pentose phosphate pathways, while increasing expression of genes regulating pyruvate dehydrogenase and long-chain fatty acyl-CoA and cholesterol biosynthesis, thereby rerouting of carbon substrates from glucose metabolism to lipid metabolism required for the biogenesis of membranes for neuronal and glial function and synaptic remodeling. Furthermore, based on the transcriptional signatures, these changes in gene expression involve neurons, astrocytes, oligodendrocytes, microglia and endothelial cells. Thus, peripheral insulin acutely and potently regulates expression of a broad network of genes involved in neurotransmission and brain metabolism. Dysregulation of these pathways could have dramatic effects in normal physiology and diabetes.

scholarly journals Peripheral Insulin Regulates a Broad Network of Gene Expression in the Hypothalamus, Hippocampus and Nucleus Accumbens

2021 ◽  
Author(s):  
Weikang Cai ◽  
Xuemei Zhang ◽  
Thiago M. Batista ◽  
Rubén García-Martín ◽  
Samir Softic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Cholesterol Biosynthesis ◽  
Peripheral Circulation ◽  
Fatty Acyl ◽  
Pentose Phosphate ◽  
Gaba A ◽  
Expression Of Genes ◽  
Pentose Phosphate Pathways ◽  
The Brain

The brain is now recognized as an insulin sensitive tissue, however, the role of changing insulin concentrations in the peripheral circulation on gene expression in the brain is largely unknown. Here we perform hyperinsulinemic-euglycemic clamp on 3-month-old male C57BL/6 mice for 3 hours. We show that increases in peripheral insulin within the physiological range regulate expression of a broad network of gene expression in the brain compared with saline-infused controls. Insulin regulates distinct pathways in the hypothalamus, hippocampus and nucleus accumbens. Insulin shows its most robust effect in the hypothalamus and regulates multiple genes involved in neurotransmission, including up-regulating expression of multiple subunits of GABA-A receptors, Na<sup>+</sup> and K<sup>+</sup> channels, and SNARE proteins; differentially modulating glutamate receptors; and suppressing multiple neuropeptides. Insulin also strongly modulates metabolic genes in the hypothalamus, suppressing genes in the glycolysis and pentose phosphate pathways, while increasing expression of genes regulating pyruvate dehydrogenase and long-chain fatty acyl-CoA and cholesterol biosynthesis, thereby rerouting of carbon substrates from glucose metabolism to lipid metabolism required for the biogenesis of membranes for neuronal and glial function and synaptic remodeling. Furthermore, based on the transcriptional signatures, these changes in gene expression involve neurons, astrocytes, oligodendrocytes, microglia and endothelial cells. Thus, peripheral insulin acutely and potently regulates expression of a broad network of genes involved in neurotransmission and brain metabolism. Dysregulation of these pathways could have dramatic effects in normal physiology and diabetes.

scholarly journals Transcriptomic Analysis of Temperature Responses of Aspergillus kawachii during Barley Koji Production

2014 ◽  
Vol 81 (4) ◽  
pp. 1353-1363 ◽  
Author(s):  
Taiki Futagami ◽  
Kazuki Mori ◽  
Shotaro Wada ◽  
Hiroko Ida ◽  
Yasuhiro Kajiwara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Citric Acid ◽  
Solid State ◽  
Pentose Phosphate ◽  
Temperature Modulation ◽  
Cultivation Temperature ◽  
Content Type ◽  
Expression Of Genes ◽  
Aspergillus Kawachii ◽  
Heat Shock Responses

ABSTRACTThe koji moldAspergillus kawachiiis used for making the Japanese distilled spirit shochu. During shochu production,A. kawachiiis grown in solid-state culture (koji) on steamed grains, such as rice or barley, to convert the grain starch to glucose and produce citric acid. During this process, the cultivation temperature ofA. kawachiiis gradually increased to 40°C and is then lowered to 30°C. This temperature modulation is important for stimulating amylase activity and the accumulation of citric acid. However, the effects of temperature onA. kawachiiat the gene expression level have not been elucidated. In this study, we investigated the effect of solid-state cultivation temperature on gene expression forA. kawachiigrown on barley. The results of DNA microarray and gene ontology analyses showed that the expression of genes involved in the glycerol, trehalose, and pentose phosphate metabolic pathways, which function downstream of glycolysis, was downregulated by shifting the cultivation temperature from 40 to 30°C. In addition, significantly reduced expression of genes related to heat shock responses and increased expression of genes related with amino acid transport were also observed. These results suggest that solid-state cultivation at 40°C is stressful forA. kawachiiand that heat adaptation leads to reduced citric acid accumulation through activation of pathways branching from glycolysis. The gene expression profile ofA. kawachiielucidated in this study is expected to contribute to the understanding of gene regulation during koji production and optimization of the industrially desirable characteristics ofA. kawachii.

scholarly journals Estudio post-mortem de las alteraciones en la expresión de RNA en el cerebro de pacientes suicidas

2020 ◽  
Author(s):  
Brenda Cabrera-Mendoza
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Gene Expression Profile ◽  
Dual Diagnosis ◽  
Expression Profile ◽  
Suicidal Behavior ◽  
Suicide Risk ◽  
Dual Pathology ◽  
Expression Of Genes ◽  
The Brain

Despite individuals with substance use disorder (SUD) have a high suicide risk, most of gene expression studies in suicide have excluded individuals with this disorder. Thus, little is known about the gene expression profile in suicides with SUD. The identification of altered biological processes in the brain of suicides with SUD is crucial in the comprehension of the SUD and suicidal behavior comorbidity. This dissertation describes the evaluation of gene expression differences in the dorsolateral prefrontal cortex of suicides and non-suicides with and without SUD.Sixty-six brain tissue samples were collected and classified in the following groups: i) 23 suicides with SUD, ii) 20 suicides without SUD, iii) 9 non-suicides with SUD and iv) 14 non-suicides without SUD. The results of this study suggest that suicides with SUD have a gene expression profile in the prefrontal cortex different from that of individuals with only one of these conditions, presenting differences in the expression of genes involved in cell proliferation and glutamatergic neurotransmission.We performed a re-analysis of the gene expression data of 38 suicides focused on dual diagnosis and suicide. Dual diagnosis is the concurrence of at least one SUD and one or more mental disorders in a given individual. Although this comorbidity is highly prevalent and is associated with adverse clinical outcomes, its neurobiology has not been elucidated. In addition, patients with dual pathology have a higher suicide risk compared to patients with only one disorder.The objective of this re-analysis was to evaluate the differences in the gene expression profile in the prefrontal cortex of suicides with dual pathology compared to suicides with a single disorder. Our results suggest an alteration in the expression of genes involved in glutamatergic neurotransmission, GABAergic neurotransmission and neurogenesis in suicides with dual diagnosis compared to suicides with a single disorder and suicides without mental comorbidities.The observed differences in gene expression in the prefrontal cortex between suicides with and without SUD, as well as suicides with dual diagnosis and a single disorder may contribute to the phenotypic and clinical discrepancies observed among these patients. The identification of molecular characteristics in the brain of individuals with suicidal behavior and psychiatric comorbidities will allow the design of preventive and therapeutic measures aimed at the adequate treatment of each comorbidity.

scholarly journals Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Cali A. Calarco ◽  
Megan E. Fox ◽  
Saskia Van Terheyden ◽  
Makeda D. Turner ◽  
Jason B. Alipio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Mitochondrial Function ◽  
Copy Number ◽  
Drug Exposure ◽  
Related Gene ◽  
Developmental Exposure ◽  
Neuronal Signaling ◽  
Mitochondrial Copy Number ◽  
The Brain

The potency of the synthetic opioid fentanyl and its increased clinical availability has led to the rapid escalation of use in the general population, increased recreational exposure, and subsequently opioid-related overdoses. The wide-spread use of fentanyl has, consequently, increased the incidence of in utero exposure to the drug, but the long-term effects of this type of developmental exposure are not yet understood. Opioid use has also been linked to reduced mitochondrial copy number in blood in clinical populations, but the link between this peripheral biomarker and genetic or functional changes in reward-related brain circuitry is still unclear. Additionally, mitochondrial-related gene expression in reward-related brain regions has not been examined in the context of fentanyl exposure, despite the growing literature demonstrating drugs of abuse impact mitochondrial function, which subsequently impacts neuronal signaling. The current study uses exposure to fentanyl via dam access to fentanyl drinking water during gestation and lactation as a model for developmental drug exposure. This perinatal drug-exposure is sufficient to impact mitochondrial copy number in circulating blood leukocytes, as well as mitochondrial-related gene expression in the nucleus accumbens (NAc), a reward-related brain structure, in a sex-dependent manner in adolescent offspring. Specific NAc gene expression is correlated with both blood mitochondrial copy number and with anxiety related behaviors dependent on developmental exposure to fentanyl and sex. These data indicate that developmental fentanyl exposure impacts mitochondrial function in both the brain and body in ways that can impact neuronal signaling and may prime the brain for altered reward-related behavior in adolescence and later into adulthood.

scholarly journals Bisphenol A and 17α-ethinylestradiol-induced transgenerational gene expression differences in the brain–pituitary–testis axis of medaka, Oryzias latipes†

2020 ◽  
Vol 103 (6) ◽  
pp. 1324-1335
Author(s):  
Albert J Thayil ◽  
Xuegeng Wang ◽  
Pooja Bhandari ◽  
Frederick S vom Saal ◽  
Donald E Tillitt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Dna Methyltransferase ◽  
Endocrine Disrupting Chemicals ◽  
Embryo Survival ◽  
Embryonic Exposure ◽  
Expression Of Genes ◽  
F2 Generation ◽  
The Brain ◽  
Generation Male

Abstract Endocrine disrupting chemicals (EDCs), such as bisphenol A (BPA) and 17α-ethinylestradiol (EE2), can have far reaching health effects, including transgenerational abnormalities in offspring that never directly contacted either chemical. We previously reported reduced fertilization rates and embryo survival at F2 and F3 generations caused by 7-day embryonic exposure (F0) to 100 μg/L BPA or 0.05 μg/L EE2 in medaka. Crossbreeding of fish in F2 generation indicated subfertility in males. To further understand the mechanisms underlying BPA or EE2-induced adult onset and transgenerational reproductive defects in males, the present study examined the expression of genes regulating the brain–pituitary–testis (BPT) axis in the same F0 and F2 generation male medaka. Embryonic exposure to BPA or EE2 led to hyperactivation of brain and pituitary genes, which are actively involved in reproduction in adulthood of the F0 generation male fish, and some of these F0 effects continued to the F2 generation (transgenerational effects). Particularly, the F2 generation inherited the hyperactivated state of expression for kisspeptin (kiss1 and kiss2) and their receptors (kiss1r and kiss2r), and gnrh and gnrh receptors. At F2 generation, expression of DNA methyltransferase 1 (dnmt1) decreased in brain of the BPA treatment lineage, while EE2 treatment lineage showed increased dnmt3bb expression. Global hypomethylation pattern was observed in the testis of both F0 and F2 generation fish. Taken together, these results demonstrated that BPA or EE2-induced transgenerational reproductive impairment in the F2 generation was associated with alterations of reproductive gene expression in brain and testis and global DNA methylation in testis.

scholarly journals Expression of genes involved in key metabolic processes during winter flounder (Pseudopleuronectes americanus) metamorphosis

2013 ◽  
Vol 91 (3) ◽  
pp. 156-163 ◽  
Author(s):  
Marie Vagner ◽  
Benjamin de Montgolfier ◽  
Jean-Marie Sévigny ◽  
Réjean Tremblay ◽  
Céline Audet
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Pentose Phosphate ◽  
Winter Flounder ◽  
Benthic Habitat ◽  
Pseudopleuronectes Americanus ◽  
Metabolic Processes ◽  
Expression Of Genes ◽  
Molecular Events ◽  
Gh Gene

The aim of this study was to better understand the molecular events governing ontogeny in winter flounder (Pseudopleuronectes americanus (Walbaum, 1792)). The expression of seven genes involved in key metabolic processes during metamorphosis were measured at settlement (S0), at 15 (S15), and 30 (S30) days after settlement and compared with those in pelagic larvae prior to settlement (PL). Two critical stages were identified: (1) larval transit from the pelagic to the benthic habitat (from PL to S0) and (2) metamorphosis maturation, when the larvae stay settled without growth (from S0 to S30). Growth hormone (gh) gene expression significantly increased at S0. At S30, an increase in cytochrome oxidase (cox) gene expression occurred with a second surge of gh gene expression, suggesting that enhanced aerobic capacity was supporting growth before the temperature decrease in the fall. Expression patterns of pyruvate kinase (pk), glucose-6-phosphate dehydrogenase (g6pd), and bile salt activated lipase (bal) genes indicated that energy synthesis may be mainly supplied through glycolysis in PL, through the pentose–phosphate pathway at settlement, and through lipid metabolism at S30. The expression of the heat-shock protein 70 (hsp70), superoxide dismutase (sod), cox, and peroxiredoxin-6 (prx6) genes revealed that oxidative stress and the consequent development of antioxidative protection were limited during the PL stage, reinforced at settlement, and very high at S30, certainly owing to the higher growth rate observed at this period.

scholarly journals Effect of organically and conventionally produced diets on jejunal gene expression in chickens

2009 ◽  
Vol 103 (5) ◽  
pp. 696-702 ◽  
Author(s):  
Astrid de Greeff ◽  
Machteld Huber ◽  
Lucy van de Vijver ◽  
Willem Swinkels ◽  
Henk Parmentier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Background ◽  
Cholesterol Biosynthesis ◽  
Transcriptional Response ◽  
Production Method ◽  
Transcriptional Level ◽  
Feed Ingredients ◽  
Expression Of Genes ◽  
Chicken Major Histocompatibility Complex ◽  
Organically Grown

Using a nutrigenomics approach we studied the response of second-generation chickens at a transcriptional level to organically grown feed ingredients compared with conventionally grown feed ingredients. Both diets consisted of the same amounts of ingredients, the only difference was the production method. Gene expression was analysed in jejuni using whole genome chicken cDNA arrays. After analysis, forty-nine genes were found to be differentially regulated between chickens fed on the different diets, independent of their genetic background. Of these forty-nine genes, seven genes were involved in cholesterol biosynthesis. Genes involved in cholesterol biosynthesis were higher expressed in jejuni from organically fed birds. Other genes found to be regulated were involved in immunological processes, such as B-G protein (part of chicken major histocompatibility complex), chemokine ah221, and the immunoglobulin heavy chain. Using quantitative PCR the effect of genetic background on the differential expression of genes was studied. Differences in gene expression existed between animals fed different diets as well as between different chicken lines. This indicated that diet and genetic background influence the transcriptional response of the jejunum. This is the first time that significant differences in gene expression were shown between animals on diets with organically or conventionally produced ingredients.

scholarly journals The Effect of Impaired Polyamine Transport on Pneumococcal Transcriptome

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1322
Author(s):  
Mary F. Nakamya ◽  
Moses B. Ayoola ◽  
Leslie A. Shack ◽  
Edwin Swiatlo ◽  
Bindu Nanduri
Keyword(s):  
Stress Responses ◽  
Nitrosative Stress ◽  
Sugar Metabolism ◽  
Pentose Phosphate ◽  
Therapeutic Interventions ◽  
Expression Of Genes ◽  
Polyamine Transport ◽  
Novel Target ◽  
Pentose Phosphate Pathways

Infections due to Streptococcus pneumoniae, a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genome plasticity, antibiotic resistance, and limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions to limit the spread of this pathogen. Pathogenic mechanisms that allow successful adaption and persistence in the host could be potential innovative therapeutic targets. Polyamines are ubiquitous polycationic molecules that regulate many cellular processes. We previously reported that deletion of polyamine transport operon potABCD, which encodes a putrescine/spermidine transporter (∆potABCD), resulted in an unencapsulated attenuated phenotype. Here, we characterize the transcriptome, metabolome, and stress responses of polyamine transport-deficient S. pneumoniae. Compared with the wild-type strain, the expression of genes involved in oxidative stress responses and the nucleotide sugar metabolism was reduced, while expression of genes involved in the Leloir, tagatose, and pentose phosphate pathways was higher in ΔpotABCD. A metabolic shift towards the pentose phosphate pathway will limit the synthesis of precursors of capsule polysaccharides. Metabolomics results show reduced levels of glutathione and pyruvate in the mutant. Our results also show that the potABCD operon protects pneumococci against hydrogen peroxide and nitrosative stress. Our findings demonstrate the importance of polyamine transport in pneumococcal physiology that could impact in vivo fitness. Thus, polyamine transport in pneumococci represents a novel target for therapeutic interventions.

A unique neurogenomic state emerges after aggressive confrontations in males of the fish Betta splendens

2020 ◽  
Author(s):  
Trieu-Duc Vu ◽  
Yuki Iwasaki ◽  
Kenshiro Oshima ◽  
Masato Nikaido ◽  
Ming-Tzu Chiu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Betta Splendens ◽  
Assessment Process ◽  
Expression Of Genes ◽  
Gradual Loss ◽  
Specific Manner ◽  
Complex Decision Making ◽  
Complex Decision ◽  
The Brain

AbstractTerritorial defense involves frequent aggressive confrontations with competitors, but little is known about how brain-transcriptomic profiles change between individuals competing for territory establishment. Our previous study elucidated that brain-transcriptomic synchronization occurs in a pair-specific manner between two males of the fish Betta splendens during fighting, reflecting a mutual assessment process between them at the level of gene expression. Here we evaluated how the brain-transcriptomic profiles of opponents change immediately after shifting their social status (i.e., the winner/loser has emerged) and 30 min after this shift. We showed that unique and carryover hypotheses can be adapted to this system, in which changes in the expression of certain genes are unique to different fighting stages and in which the expression patterns of certain genes are transiently or persistently changed across all fighting stages. Interestingly, the specificity of the brain-transcriptomic synchronization of a pair during fighting was gradually lost after fighting ceased, because of the decrease in the variance in gene expression across all individuals, leading to the emergence of a basal neurogenomic state. Strikingly, this unique state was more basal than the state that existed in the before-fighting group and resulted in the reduced and consistent expression of genes across all individuals. In spite of the consistent and basal overall gene expression in each individual in this state, expression changes for genes related to metabolism, learning and memory, and autism still differentiated losers from winners. The fighting system using male B. splendens thus provides a promising platform for investigating neurogenomic states of aggression in vertebrates.Author summaryCompetitive interactions involve complex decision-making tasks that are shaped by mutual feedback between participants. When two animals interact, transcriptomes across their brains synchronize in a way that reflects how they assess and predict the other’s fighting ability and react to each other’s decisions. Here, we elucidated the gradual loss of brain-transcriptomic synchrony between interacting opponents after their interaction ceased, leading to the emergence of a basal neurogenomic state, in which the variations in gene expression were reduced to a minimum among all individuals. This basal neurogenomic state shares common characteristics with the hibernation state, which animals adopt to minimize their metabolic rates to cope with harsh environmental conditions. We demonstrated that this unique neurogenomic state, which is newly characterized in the present study, is composed of the expression of a unique set of genes, each of which was presumably minimally required for survival, providing a hypothesis that this state represents the smallest unit of neurogenomic activity for sustaining an active life.

scholarly journals Postweaning Iron Deficiency in Male Rats Leads to Long-Term Hyperactivity and Decreased Reelin Gene Expression in the Nucleus Accumbens

2019 ◽  
Author(s):  
Noriko Nishikura ◽  
Kodai Hino ◽  
Tomoko Kimura ◽  
Yasuhiro Uchimura ◽  
Shinjiro Hino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Iron Deficiency ◽  
Male Rats ◽  
Juvenile Period ◽  
Synaptic Density ◽  
Adequate Diet ◽  
Age Related ◽  
The Brain

ABSTRACT Background Epidemiological research indicates that iron deficiency (ID) in infancy correlates with long-term cognitive impairment and behavioral disturbances, despite therapy. However, the mechanisms underlying these effects are unknown. Objective We investigated how ID affected postweaning behavior and monoamine concentration in rat brains to determine whether ID during the juvenile period affected gene expression and synapse formation in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Methods Fischer 344/Jcl postweaning male rats aged 21–39 d were fed low-iron diets (0.35 mg/kg iron; ID group) or standard AIN-93 G diets [3.5 mg/kg iron; control (CN) group]. After day 39, all rats were fed the iron-adequate diet. The locomotor activity was evaluated by the open field and elevated plus maze tests at 8 and 12 wk of age. Monoamine concentrations in the brain were analyzed using HPLC at 9 and 13 wk of age. Comprehensive gene expression analysis was performed in the PFC and NAcc at 13 wk of age. Finally, we investigated synaptic density in the PFC and NAcc by synaptophysin immunostaining. Results Behavioral tests revealed a significant reduction of the age-related decline in the total distance traveled in ID rats compared with CN rats (P < 0.05), indicating that ID affected hyperactivity, which persisted into adulthood (13 wk of age). At this age, reelin (Reln) mRNA expression (adjusted P < 0.01) decreased and synaptic density (P < 0.01) increased in the NAcc in the ID group. Regarding the mesolimbic pathway, homovanillic acid concentration increased in the NAcc, whereas the dopamine concentration decreased in the ventral midbrain. Conclusions Our results suggest that ID during the postweaning period in male rats, despite complete iron repletion following ID, led to long-term hyperactivity via monoamine disturbance in the brain and an alteration in the synaptic plasticity accompanied by downregulation of Reln expression in the NAcc.

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