WorldWideScience

Sample records for brain inos expressing

  1. Prodigiosin inhibits gp91phox and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia–ischemia

    International Nuclear Information System (INIS)

    This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen–glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100 μg/kg, i.v.) at 1 h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91phox), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood–brain barrier (BBB) by activation of nuclear factor-kappa B (NF-κB). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91phox and iNOS via activation of the NF-κB pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91phox and iNOS expression possibly by impairing NF-κB activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosin's protective effect in the MCAo/r mice. -- Highlights: ► Prodigiosin ameliorated brain infarction and deficits. ► Prodigiosin protected against hypoxia/reperfusion-induced brain injury. ► Prodigiosin diminished oxidative/nitrosativestress and leukocytes infiltration. ► Prodigiosin reduced BBB breakdown. ► Prodigiosin down-regulated gp91phox and iNOS by inhibiting NF-κB activation.

  2. Serum albumin induces iNOS expression and NO production in RAW 267.4 macrophages

    OpenAIRE

    Poteser, Michael; Wakabayashi, Ichiro

    2004-01-01

    We investigated the effects of serum albumin on inducible nitric oxide synthase (iNOS) expression in RAW 267.4 macrophages. Crude fraction-V type albumin as well as bovine serum albumin filtrated for endotoxin induced concentration-dependent iNOS expression in macrophages. Accordingly, NO production (estimated by supernatant nitrite) was markedly (up to 10-fold) increased in the presence of albumin.Albumin-induced expression of iNOS protein was inhibited by cycloheximide and NO production was...

  3. Role of p38 MAPK in lipopolysaccharide-induced iNOS expression by endothelial cells

    Institute of Scientific and Technical Information of China (English)

    KAN Wen-hong; YAN Wen-sheng; JIANG Yong; WANG Jing-zhen; QIN Qing-he; ZHAO Ke-seng

    2002-01-01

    Objective:To examine the role of p38 mitogen-activated protein kinase (MAPK) in NO production and Inos expression in human endothelial cells stimulated by lipopolysaccharide (LPS). Methods: The NO level in the supernatant of the cell culture media was measured with Griess method, expressions of Inos protein and Mrna in vitro cultured endothelial cell line ECV304 were detected with immunofluorescence analysis and reverse transcriptase-PCR respectively. Immunokinase assay was employed to measure P38mapk activity. Results: Compared with the basal level of Inos expression and NO production, the NO level and the expressions of Inos Mrna and protein in the cells were increased after LPS stimulation. P38mapk activity in ECV304 cells exhibited a marked increase at 15 min after LPS stimulation, lasting for about 45 min before gradually decline. The Inos protein and Mrna expressions induced by LPS stimulation was significantly inhibited by SB203580 [4-(4-fluorophenyl)-2-(4- methylsulfinylphenyl)-5-(4-pyridyl) imidazole], a highly specific inhibitor of p38 MAPK. Conclusion: p38 MAPK plays an important role in iNOS expression and NO production in ECV304 cells, and the inhibition of the signal transduction pathway can be effective to reduce the production of iNOS and other cytokines, and therefore constitutes a useful strategy for treating septic shock or inflammation.

  4. The research of the express of swimming exercise towards the nNOSmRAN iNOS mRNA of the Diabetes Rats Brain%游泳训练对糖尿病大鼠脑nNOSmRNA,iNOS mRNA的表达研究

    Institute of Scientific and Technical Information of China (English)

    景旺; 王轲

    2011-01-01

    Aim To detect the effect of swimming exercise on the cognitive ability of rats with diabetics and the expression of iNOS mRNA and nNOS mRNA in brain. Methods The rat diabetes model was inducod by injecting streptozocin, and then the rats were randomly divided into three groups: control group, diabetes mellitus untreated group and swimming exercise group. After six weeks of swimming exercise treatment, memory was examined with the device of Morris water maze. The expression of iNOS mRNA and nNOS mRNA in brain was detected. Results The rats in swimming exercise group showed an increase of learning ability ( P < 0. 05 ) with more expression of nNOS mRNA ( P < 0. 05 ) and a weaker expression of iNOS mRNA ( P < 0. 05 ). Conclusion Swimming exercise can decrease the expression of iNOS mRNA and increase the expression of nNOS mRNA, swimming exercise can improve diabetes rats' abilities of learning and memory.%目的 观察游泳训练对糖尿病大鼠学习记忆功能及iNOS,nNOS mRNA表达的影响.方法 选用雄性SD大鼠40只,随机分为正常对照组、模型对照组、游泳训练组.采用链脲佐菌素静脉注射复制糖尿病模型,游泳训练组运动6周后应用Morris水迷宫法观察游泳训练对糖尿病大鼠学习记忆的影响,并测定大鼠脑组织iNOS mRNA和nNOS mRNA的表达.结果 游泳训练组大鼠脑组织iNOS mRNA显著低于模型对照组,nNOS mRNA显著高于模型对照组.结论 游泳训练能增加糖尿病大鼠脑组织nNOS mRNA含量,降低iNOS mRNA.从而对糖尿病大鼠学习与记忆障碍有一定程度的改善.

  5. Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice

    International Nuclear Information System (INIS)

    Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 μg/m3 of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae were mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-κB (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-κB (p65) was determined by real-time PCR. Results: DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by ∼ 20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-κB was significantly augmented after DE exposure. NF-κB activity was enhanced 2-fold after DE inhalation, and the augmented NF-κB activity was positively correlated with iNOS expression (R2 = 0.5998). Conclusions: We show that exposure to DE increases iNOS expression and activity possibly via NF-κB-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality. - Highlights: → Exposed ApoE knockout mice (30-week) to diesel exhaust (DE) for 7 weeks. → Examine iNOS expression and activity in the blood vessels and heart. → DE exposure enhanced

  6. Expression of NRAMP1 and iNOS in Mycobacterium avium subsp. paratuberculosis naturally infected cattle.

    Science.gov (United States)

    Delgado, F; Estrada-Chávez, C; Romano, M; Paolicchi, F; Blanco-Viera, F; Capellino, F; Chavez-Gris, G; Pereira-Suárez, A L

    2010-09-01

    Paratuberculosis (PTB) is a chronic disease caused by M. avium subsp. paratuberculosis (MAP) that affects several animal species, and some studies have suggested that there may be a relationship between Crohn's disease and PTB. Significant aspects of PTB pathogenesis are not yet completely understood, such as the role of macrophages. Natural resistance-associated macrophage protein 1 (NRAMP1) and the inducible nitric oxide synthase (iNOS) molecules have shown nonspecific effects against several intracellular pathogens residing within macrophages. However, these molecules have been scarcely studied during natural infection with MAP. In this work, changes in NRAMP1 and iNOS expression were surveyed by immunohistochemistry in tissue samples from MAP-infected cattle and healthy controls. Our findings show strong specific immunolabeling against both NRAMP1 and iNOS molecules, throughout granulomatous PTB-compatible lesions in ileum and ileocaecal lymph nodes from paratuberculous cattle compared with uninfected controls, suggesting a relationship between the expression of these molecules and the pathogenesis of PTB disease. PMID:19345998

  7. Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum.

    Science.gov (United States)

    Di Girolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

    2003-07-01

    1. The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. 2. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. 3. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg(-1), i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. 4. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. 5. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. 6. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury. PMID:12871835

  8. Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue lymphoma

    Institute of Scientific and Technical Information of China (English)

    Hong-Ling Li; Bing-Zhong Sun; Fu-Cheng Ma

    2004-01-01

    AIM:To assess the expression of cyclooxygenase-2 (COX-2),nitric oxide synthase (iNOS), p53 and Ki-67 in gastric mucosaassociated lymphoid tissue (MALT) lymphoma and clarify the relationship between COX-2 expression and iNOS or p53 expression in these patients.METHODS: The expressions of COX-2, iNOS, p53 and Ki-67 were detected in 32 gastric MALT lymphoma specimens and 10 adjacent mucosal specimens by immunohistochemical Envision method.RESULTS: COX-2 and iNOS expressions were significantly higher in gastric MALT lymphoma tissues than those in adjacent normal tissues. The expression of COX-2 was observed in 22 of 32 cases of MALT lymphoma tissues(68.8%). A positive cytoplasmic immunoreactivity for iNOS was detected in 17 of 31 cases (53.1%). COX-2 expression in gastric MALT lymphoma tissues was positively correlated with iNOS expression (r=0.448, P=0.010) and cell proliferative activity analyzed by Ki-67 labeling index (r=0.410, P=0.020).The expression of COX-2 protein did not correlate with age,sex, stage of disease, lymph node metastasis or differentiation.The accumulation of p53 nuclear phosphoprotein was detected in 19(59.4%) of tumors. p53 protein was expressed in 11 of 23 assessed LG tumors and in 8 of 9 assessed HG tumors.The difference of p53 positivity was found statistically significant between LG and HG cases (P=0.0302). The p53 accumulation correlated with advanced clinical stage (stage Ⅲ+Ⅳ vs stage Ⅰ+Ⅱ, P=-0.017). There was a significant positive correlation between COX-2 expression and p53 accumulation status (r=0.403, P=0.022). The mean PI of Ki-67 in each grade group were 36.0±7.73% in HG and 27.4±9.21% in LG. High-proliferation rate correlated with HG tumors (r=0.419, P=0.017). The correlation coefficient showed a significant positive correlation between PI and COX-2 expression in MALT lymphoma patients (r=0.410,P=0.020).CONCLUSION: COX-2 expresses in the majority of gastric MALT lymphoma tissues and correlates with cellular

  9. Post-transcriptional regulation of the human inducible nitric oxide synthase (iNOS) expression by the cytosolic poly(A)-binding protein (PABP).

    Science.gov (United States)

    Casper, Ingrid; Nowag, Sebastian; Koch, Kathrin; Hubrich, Thomas; Bollmann, Franziska; Henke, Jenny; Schmitz, Katja; Kleinert, Hartmut; Pautz, Andrea

    2013-09-01

    Affinity purification using the 3'-untranslated region (3'-UTR) of the human inducible nitric oxide synthase (iNOS) mRNA identified the cytosolic poly(A)-binding protein (PABP) as a protein interacting with the human iNOS 3'-UTR. Downregulation of PABP expression by RNA interference resulted in a marked reduction of cytokine-induced iNOS mRNA expression without changes in the expression of mRNAs coding for the major subunit of the RNA polymerase II (Pol 2A) or β2-microglobuline (β2M). Along with the mRNA also iNOS protein expression was reduced by siPABP-treatment, whereas in the same cells protein expression of STAT-1α, NF-κB p65, or GAPDH was not altered. Reporter gene analyses showed no change of the inducibility of the human 16kb iNOS promoter in siPABP cells. In contrast, the siPABP-mediated decline of iNOS expression correlated with a reduction in the stability of the iNOS mRNA. As the stability of the Pol 2A and β2M mRNA was not changed, siPABP-treatment seems to have a specific effect on iNOS mRNA decay. UV-crosslinking experiments revealed that PABP interacts with one binding site in the 5'-UTR and two different binding sites in the 3'-UTR of the human iNOS mRNA. Mutation or deletion of the binding site in the 5'-UTR but not in the 3'-UTR reduced luciferase expression in DLD-1 cells transfected with iNOS-5'-UTR or iNOS-3'-UTR luciferase reporter constructs. In summary, our data demonstrate that PABP by binding to specific sequence elements in the 5'-UTR post-transcriptionally enhances human iNOS mRNA stability and thereby iNOS expression. PMID:23711718

  10. The Effect of Garlic Extract on Expression of INFγ And Inos Genes in Macrophages Infected with Leishmania Major

    Directory of Open Access Journals (Sweden)

    E Bandani

    2011-09-01

    Full Text Available Background: The study was aimed to show the effect of molecular mechanism of Aqueous Garlic Extract (AGE on expression of IFNγ and iNOS genes in Leishmania major.Methods: Leishmania major promastigotes (MRHO/IR/75/ER were added to the in-vitro cultured J774 cell line, the cells were incubated for 72 hours. Various concentrations of garlic extract (9.25, 18.5, 37, 74, 148 mg/ml were added to the infected cells. MTT assay was applied for cellular proliferation. After 72 hours of incubation, supernatants were collected and total RNA was extracted from the infected cells. The express of IFNγ and iNOS genes were studied by RT-PCR method.Results: The colorimetric MTT assay after 3 days of incubation showed cytotoxic effect of garlic extract with an IC50 of 37 mg/ml. In addition, IFNγ and iNOS genes expression by RT-PCR indicated that garlic extract lead to over expression of these genes in J774 cell line infected with L. major.Conclusion: Garlic extract exerts cytotoxic effect on infected J774 cell line. In addition, the hypothesis that garlic can improve cellular immunity with raising the expression of IFNγ and of iNOS genes con­firmed.

  11. Myosin V and iNOS expression is enhanced in J774 murine macrophages treated with IFN-gamma

    Directory of Open Access Journals (Sweden)

    D.S. Reis

    2001-02-01

    Full Text Available Actin-based motor protein requirements and nitric oxide (NO production are important features of macrophage activity during phagocytosis or microbicidal processes. Different classes of myosins contribute directly or indirectly to phagocytosis by providing mechanical force for phagosome closure or organelle movement. Recent data have shown the presence of myosins IC, II, V and IXb in phagosomes of bone marrow-derived murine macrophages. In our investigation we demonstrated the presence of different classes of myosins in J774 macrophages. We also analyzed the effect of gamma interferon (IFN-gamma, with or without calcium ionophore or cytochalasin B, on myosins as well as on inducible nitric oxide synthase (iNOS expression and NO production. Myosins IC, II, Va, VI and IXb were identified in J774 macrophages. There was an increase of myosin V expression in IFN-gamma-treated cells. iNOS expression was increased by IFN-gamma treatment, while calcium ionophore and cytochalasin B had a negative influence on both myosin and iNOS expression, which was decreased. The increases in NO synthesis were reflected by increased iNOS expression. Macrophages activated by IFN-gamma released significant amounts of NO when compared to control groups. In contrast, NO production by calcium ionophore- and cytochalasin B-treated cells was similar to that of control cells. These results suggest that IFN-gamma is involved in macrophage activation by stimulating protein production to permit both phagocytosis and microbicidal activity.

  12. Aloe vera toxic effects: expression of inducible nitric oxide synthase (iNOS) in testis of Wistar rat

    OpenAIRE

    Samira Asgharzade; Mahmoud Rafieian-kopaei; Amin Mirzaeian; Somaye Reiisi; Loghman Salimzadeh

    2015-01-01

    Objective(s): Nitric oxide (NO), a product of inducible nitric oxide synthase (iNOS), contributes in germ cell apoptosis. This study was aimed to evaluate the effects of Aloe vera gel (AVG) on male Wistar rat reproductive organ, serum NO level, and expression of iNOS gene in leydig cells. Materials and Methods: Adult male Wistar rats (n=36) were used for experiments in three groups. The experimental groups were orally administered with the AVG extract solution once-daily as follow: 150 mg.kg-...

  13. Expression of iNOS in early injury in a rat model of small-for-size liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Wei-Wei Jiang; Lian-Bao Kong; Guo-Qiang Li; Xue-Hao Wang

    2009-01-01

    BACKGROUND: Living donor liver transplantation has been widely accepted as the treatment of choice for end-stage liver disease. Large amounts of nitric oxide generated by inducible nitric oxide synthase (iNOS) have been shown to play an important role in many inlfammatory and immune reactions, but expression of iNOS in small-for-size liver transplantation is unknown. The aims of this study were to determine the time course of iNOS mRNA and protein as well as the redox state of liver biopsies in a rat model of small-for-size liver transplantation. METHODS: Male Sprague-Dawley rats were divided into a control group, a warm ischemia-reperfusion (IR) group, and a small-for-size liver graft group. Real-time RT-PCR and Western blotting were used to characterize the time course of the expression of iNOS mRNA and protein, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) were used as markers to characterize the redox state of liver tissues, and the time courses of MDA and SOD levels were also measured. RESULTS: The expression of iNOS mRNA and protein levels in the warm IR and small-for-size graft groups both signiifcantly increased after reperfusion, and peaked at 3 hours. Moreover, the increase in MDA was accompanied by increased iNOS in the period of 1-24 hours after reperfusion. The MDA levels in the warm IR and small-for-size graft groups signiifcantly increased after reperfusion, peaked at 3 hours, and decreased thereafter. The direction of change in SOD was opposite that of the change in MDA.CONCLUSIONS: The expression of iNOS mRNA and protein is activated after reperfusion both in hepatic warm IR injury and small-for-size liver graft. Furthermore, the results of this study suggest that iNOS contributes to the damage in warm IR injury and small-for-size grafts via free oxygen radicals.

  14. Inflammatory modulating effects of low level laser therapy on iNOS expression by means of bioluminescence imaging

    Science.gov (United States)

    Moriyama, Yumi; Moriyama, Eduardo H.; Blackmore, Kristina; Akens, Margarete K.; Lilge, Lothar

    2005-09-01

    This study investigates the efficacy of low level laser therapy (LLLT) in modulating inducible nitric oxide synthase (iNOS) expression as molecular marker of the inflammation signaling pathway. LLLT was mediated by different therapeutic wavelengths using transgenic animals with the luciferase gene under control of the iNOS gene expression. Inflammation in 30 transgenic mice (iNOS-luc mice, from FVB strain) was induced by intra-articular injection of Zymosan-A in both knee joints. Four experimental groups were treated with one of four different wavelengths (λ=635, 785, 808 and 905nm) and one not laser-irradiated control group. Laser treatment (25 mW cm-2, 5 J cm-2) was applied to the knees 15 minutes after inflammation induction. Measurements of iNOS expression were performed at multiple times (0, 3, 5, 7, 9 and 24h) post-LLLT by measuring the bioluminescence signal using a highly sensitive charge-coupled device (CCD) camera. The responsivity of BLI was sufficient to demonstrate a significant increase in bioluminescence signals after laser irradiation of 635nm when compared to non-irradiated animals and the other LLLT treated groups, showing the wavelength-dependence of LLLT on iNOS expression during the acute inflammatory process.

  15. The effect of high protein diet and exercise on irisin, eNOS, and iNOS expressions in kidney.

    Science.gov (United States)

    Tastekin, Ebru; Palabiyik, Orkide; Ulucam, Enis; Uzgur, Selda; Karaca, Aziz; Vardar, Selma Arzu; Yilmaz, Ali; Aydogdu, Nurettin

    2016-08-01

    Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies. PMID:27277302

  16. Tumor-expressed iNOS controls induction of functional myeloid derived suppressor cells (MDSC) through modulation of VEGF release1

    OpenAIRE

    Jayaraman, Padmini; Parikh, Falguni; Lopez-Rivera, Esther; Hailemichael, Yared; Clark, Amelia; Ma, Ge; Cannan, David; Ramacher, Marcel; Kato, Masashi; Overwijk, Willem W.; Chen, Shu-hsia; Umansky, Viktor Y.; Sikora, Andrew G.

    2012-01-01

    Inducible nitric oxide synthase (iNOS) is a hallmark of chronic inflammation which is also overexpressed in melanoma and other cancers. While iNOS is a known effector of myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, its pivotal position at the interface of inflammation and cancer also makes it an attractive candidate regulator of MDSC recruitment. We hypothesized that tumor-expressed iNOS controls MDSC accumulation and acquisition of suppressive activity in melanoma. CD11...

  17. Construction of A Eukaryotic Expression Vector Carrying the iNOS Gene and Its Effect on A549 Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sujuan YE

    2012-05-01

    Full Text Available Background and objective The iNOS gene is associated with NO-mediated antitumor effects. The aims of this study are to construct a eukaryotic expression plasmid that carries the iNOS gene and to detect the expression levels and antitumor effects of the iNOS gene on A549 lung cancer cells. Methods A DNA fragment of the human iNOS coding sequence was amplified using reverse transcription polymerase chain reaction (RT-PCR. The DNA fragment was subsequently cloned into the multiple cloning sites of the eukaryotic expression vector pVAX. The recombinant plasmid was confirmed using restriction enzyme treatment, PCR, and sequencing and was then transfected into A549 lung cancer cells. The expression of the iNOS gene in the A549 lung cancer cells after transfection was verified by RT-PCR and Western blot analysis. The effects of iNOS on cell apoptosis, proliferation, and migration were identified by staining with Hoechst 3235, an MTT assay, and a scratch assay, respectively. Results The results of the restriction enzyme digestion, PCR, and sequencing verified the successful construction of the eukaryotic expression plasmid pVAX-iNOS. The iNOS gene expression level was increased in the transfected A549 cells. Further experiments also showed increased cell apoptosis among the A549 lung cancer cells transfected with pVAX-iNOS. Meanwhile, the proliferation and migration of A549 cells were significantly inhibited by the enhanced iNOS gene expression. Conclusion The recombinant eukaryotic expression vector pVAX-iNOS was successfully constructed and transfected into A549 cells. The enhanced iNOS gene expression significantly promoted cell apoptosis, whereas the proliferation and migration of A549 cells were inhibited. These findings contribute to the development of novel and effective gene therapies for lung cancer.

  18. ER stress upregulated PGE2/IFNγ-induced IL-6 expression and down-regulated iNOS expression in glial cells

    Science.gov (United States)

    Hosoi, Toru; Honda, Miya; Oba, Tatsuya; Ozawa, Koichiro

    2013-12-01

    The disruption of endoplasmic reticulum (ER) function can lead to neurodegenerative disorders, in which inflammation has also been implicated. We investigated the possible correlation between ER stress and immune function using glial cells. We demonstrated that ER stress synergistically enhanced prostaglandin (PG) E2 + interferon (IFN) γ-induced interleukin (IL)-6 production. This effect was mediated through cAMP. Immune-activated glial cells produced inducible nitric oxide synthase (iNOS). Interestingly, ER stress inhibited PGE2 + IFNγ-induced iNOS expression. Similar results were obtained when cells were treated with dbcAMP + IFNγ. Thus, cAMP has a dual effect on immune reactions; cAMP up-regulated IL-6 expression, but down-regulated iNOS expression under ER stress. Therefore, our results suggest a link between ER stress and immune reactions in neurodegenerative diseases.

  19. Rutin improves endotoxin-induced acute lung injury via inhibition of iNOS and VCAM-1 expression.

    Science.gov (United States)

    Huang, Yi-Chun; Horng, Chi-Ting; Chen, Shyan-Tarng; Lee, Shiuan-Shinn; Yang, Ming-Ling; Lee, Chien-Ying; Kuo, Wu-Hsien; Yeh, Chung-Hsin; Kuan, Yu-Hsiang

    2016-02-01

    Endotoxins exist anywhere including in water pools, dust, humidifier systems, and machining fluids. The major causal factor is endotoxins in many serious diseases, such as fever, sepsis, multi-organ failure, meningococcemia, and severe morbidities like neurologic disability, or hearing loss. Endotoxins are also called lipopolysaccharide (LPS) and are important pathogens of acute lung injury (ALI). Rutin has potential beneficial effects including anti-inflammation, antioxidation, anti-hyperlipidemia, and anti-platelet aggregation. Pre-treatment with rutin inhibited LPS-induced neutrophil infiltration in the lungs. LPS-induced expression of vascular cell adhesion molecule (VCAM)-1 and inducible nitric oxide synthase (iNOS) was suppressed by rutin, but there was no influence on expression of intercellular adhesion molecule-1 and cyclooxygenase-2. In addition, activation of the nuclear factor (NF)κB was reduced by rutin. Furthermore, we found that the inhibitory concentration of rutin on expression of VCAM-1 and iNOS was similar to NFκB activation. In conclusion, rutin is a potential protective agent for ALI via inhibition of neutrophil infiltration, expression of VCAM-1 and iNOS, and NFκB activation. PMID:25080890

  20. Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide

    OpenAIRE

    Chiou, Wen-Fei; Chen, Chieh-Fu; Lin, Jin-Jung

    2000-01-01

    Andrographolide, an active component found in leaves of Andrographis paniculata, has been reported to exhibit nitric oxide (NO) inhibitory property in endotoxin-stimulated macrophages, however, the detailed mechanisms remain unclear. In the present study we investigated the effect of andrographolide on the expression of inducible NO synthase (iNOS) mRNA, protein, and enzyme activity in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) plus interferon-γ (IFN-γ).RAW 264.7 cells sti...

  1. Effects of Bilirubin on Alveolar Macrophages in Rats with Emphysema and Expression of iNOS and NO in Them

    Institute of Scientific and Technical Information of China (English)

    李建强; 赵卉; 宋满景; 徐永健; 张珍祥

    2004-01-01

    To explore the effects of bilirubin on alveolar macrophages (AM) and expression of iNOS and NO in them in emphysema model, the rats were pretreated with bilirubin before exposed to smoke. AM were isolated from bronchoalveolar lavage fluid (BALF) and cultured. Pathological microscopic examination of AM and immunohistochemical analysis of iNOS were performed. Nitric oxide (NO) content in the samples was determined by nitrate reductase technique. The results showed both alveoli and alveolar septum appeared normal in size and shape in normal group. AM showed kidney-shaped nucleus and were rich in Golgi complexes and primary lysosomes in the cytoplasm. The inner membrane of mitochondrion was continuous. Most cristae of the mitochondria were intact. In model group, the alveoli were expanded, ruptured and bullaes were formed. Both the population and sizes of AM increased significantly. Secondary lysosomes were rich in the cytoplasm. Deformation and pyknosis of the nucleus, swelling of the mitochondrions and rupture of the inner mitochondrial membrane could also be seen. At high magnification, most of the mitochondrial cristae were broken, or completely lost at certain points. In bilirubin group, alveoli partly expanded and the population of AM also increased, with morphological changes being slighter than that in model group. Both NO contents and expression of iNOS in model group were higher than those in normal group (P<0.05). In bilirubin group the two indice were lower than those in model group (P<0.05). Our findings suggested that high expression of iNOS and high NO content in AM accelerate the development of emphysema associated with smoking in rats. Bilirubin may exert protective effects on AM and retards the development of emphysema in rats.

  2. Expression of inflammation related factors iNOS and ICAM-1 in endothelial cells induced by C-reactive protein

    Directory of Open Access Journals (Sweden)

    Xu-dong SONG

    2011-08-01

    Full Text Available Objective To investigate the expression of inducible nitric oxide synthase(iNOS and intercellular cell adhesion molecule-1(ICAM-1 in endothelial cells induced by C-reactive protein(CRP and its corresponding mechanisms.Methods Human umbilical cord vein endothelial cells(HUVEC were treated with different concentrations of CRP or with phosphate buffered solution as control,and RT-PCR was used for measurement of the expression of ICAM-1 mRNA induced by CRP in HUVECs.HUVEC were treated with CRP of 1mg/L,5mg/L,20mg/L,or with phosphate buffered solution,and expressions of ICAM-1 and iNOS protein in HUVECs were detected by cellular enzyme linked immunosorbent assay(ELISA.Results In groups of 1mg/L,5mg/L and 10mg/L CRP,no different effects on expression of ICAM-1 mRNA in HUVECs was found when compared with control group,whereas the expression of ICAM-1 mRNA was elevated in the group of 20mg/L CRP by 1.48 folds compared with that in control group.Similarly,in groups of 1mg/L and 5mg/L CRP there was no significant difference in the expressions of ICAM-1 and iNOS in HUVECs compared with that in control group(P > 0.05,whereas the expressions of ICAM-1 and iNOS protein were increased significantly in group of 20mg/L CRP compared with that in other groups(P< 0.01.Conclusions Although CRP may induce the expression of inflammatory factors in endothelial cells,the present experioment showed that CRP had no significant effects on inflammatory factors in endothelial cells at normal physiological level,and it gave inducible effects at higher concentration(20mg/L only.

  3. PPARgamma inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in rats.

    Science.gov (United States)

    Lin, Tzu-Hung; Yang, Rong-Sen; Tang, Chih-Hsin; Lin, Chih-Peng; Fu, Wen-Mei

    2007-10-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated transcription factor, is considered as an anti-osteoblastic factor associated with adiposity and the elderly osteoporosis due to a defect in osteoblastogenesis. We have found that oral administration of PPARgamma activator rosiglitazone decreased tibia BMD and serum ALP but left serum calcium and osteoclast marker C-terminal telopeptide unaffected. In addition, we examined the inhibitory mechanisms of PPARgamma on the bone formation by using PPARgamma activators ciglitazone and 15-deoxy-Delta(12,14)-prostaglandin-J2 (15d-PGJ2). Our data indicated that PPARgamma ligands decreased both mineralized bone nodules and alkaline phosphatase (ALP) activities in cultured primary osteoblasts. Reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of bone morphogenetic protein-2 (BMP-2) and osteocalcin (OCN) was inhibited by ciglitizone and 15d-PGJ2. Furthermore, PPARgamma ligands inhibited NF-kappaB associated downstream COX-2 and iNOS osteogenic signaling. The ultrasound (US)-induced elevation of COX-2 and iNOS expression and nitric oxide (NO) production were attenuated in the presence of PPARgamma ligands. Furthermore, local administration of PPARgamma ligands into the metaphysis of rat tibia decreased the bone volume in secondary spongiosa. These results suggest that the activation of PPARgamma inhibits osteoblastic differentiation and the expression of several anabolic mediators involved in bone formation. These data may reflect osteoporosis and less bone formation in the aging people and patients treated with thiazolidinediones. PMID:17669705

  4. Echinocystic Acid Inhibits IL-1β-Induced COX-2 and iNOS Expression in Human Osteoarthritis Chondrocytes.

    Science.gov (United States)

    Ma, Zhiqiang; Wang, Yanlong; Piao, Taikui; Liu, Jianyu

    2016-04-01

    Echinocystic acid (EA), a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, displays a range of pharmacological activities including anti-inflammatory and antioxidant effects. However, the effect of EA on IL-1β-stimulated osteoarthritis chondrocyte has not been reported. The purpose of this study was to assess the effects of EA on IL-1β-stimulated human osteoarthritis chondrocyte. Chondrocytes were stimulated with IL-1β in the absence or presence of EA. NO and PGE2 production were measured by Griess reagent and ELISA. The expression of COX-2, iNOS, nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) were detected by Western blot analysis. The results showed that EA suppressed IL-1β-induced collagenase-3 (MMP-13), NO, and PGE2 production in a dose-dependent manner. IL-1β up-regulated the expression of COX-2 and iNOS, and the increase was inhibited by EA. Furthermore, IL-1β-induced NF-κB and mitogen-activated protein kinase (MAPK) activation were inhibited by EA. In conclusion, EA effectively attenuated IL-1β-induced inflammatory response in osteoarthritis chondrocyte which suggesting that EA may be a potential agent in the treatment of osteoarthritis. PMID:26499345

  5. Expression of TLR4/iNOS pathway molecules in high-risk HPV-positive cervical cancer tissue and cell lines and its significance

    Institute of Scientific and Technical Information of China (English)

    Ding Wang; Zhi-Ying Li; Jiao Lu

    2016-01-01

    Objective:To study the expression of TLR4/iNOS pathway molecules in high-risk HPV-positive cervical cancer tissue and cell lines and its significance.Methods: 35 cases of patients with high-risk HPV-positive cervical cancer and 35 cases of healthy subjects receiving cervical biopsy were enrolled for study, and mRNA contents of TLRs and NOS in cervical tissue were analyzed. CaSki cell lines (HPV16-positive), Hela cell lines (HPV18-positive) and C33a cell lines (HPV-negative) were cultured, siRNA was transfected and contents of TLR4, NF-kB, iNOS and NO were detected.Results:mRNA contents of TLR4 and iNOS in high-risk HPV-positive cervical cancer tissue were significantly higher than those in normal cervical biopsy tissue, and comparison of mRNA contents of TLR3, TLR7, TLR8, TLR9, eNOS and nNOS with normal cervical biopsy tissue showed no significant differences; mRNA contents of TLR4, NF-kB and iNOS as well as NO levels in CaSki cell lines and Hela cell lines were higher than those in C33a cell lines; after transfection of TLR4 siRNA, mRNA contents of NF-kB and iNOS as well as NO levels in CaSki cell lines and Hela cell lines were lower than those transfected with negative control siRNA.Conclusions: Expression of TLR4/iNOS pathway molecules in high-risk HPV-positive cervical cancer tissue and cell lines increases, and TLR4 can increase iNOS expression and NO generation through NF-kB, thus participating in pathological process of cervical cancer caused by high-risk HPV.

  6. JAK Inhibitors AG-490 and WHI-P154 Decrease IFN- γ -Induced iNOS Expression and NO Production in Macrophages

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available In inflammation, inducible nitric oxide synthase (iNOS produces nitric oxide (NO, which modulates inflammatory processes. We investigated the effects of Janus kinase (JAK inhibitors, AG-490 and WHI-P154, on iNOS expression and NO production in J774 murine macrophages stimulated with interferon- γ (IFN- γ . JAK inhibitors AG-490 and WHI-P154 decreased IFN- γ -induced nuclear levels of signal transducer and activator of transcription 1 α (STAT1 α . JAK inhibitors AG-490 and WHI-P154 decreased also iNOS protein and mRNA expression and NO production in a concentration-dependent manner. Neither of the JAK inhibitors affected the decay of iNOS mRNA when determined by actinomycin D assay. Our results suggest that the inhibition of JAK-STAT1-pathway by AG-490 or WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN- γ -stimulated macrophages.

  7. Inducible nitric oxide synthase (iNOS expression in monocytes during acute Dengue Fever in patients and during in vitro infection

    Directory of Open Access Journals (Sweden)

    Cerqueira Denise IS

    2005-08-01

    Full Text Available Abstract Mononuclear phagocytes are considered to be main targets for Dengue Virus (DENV replication. These cells are activated after infection, producing proinflammatory mediators, including tumour-necrosis factor-α, which has also been detected in vivo. Nitric oxide (NO, usually produced by activated mononuclear phagocytes, has antimicrobial and antiviral activities. Methods The expression of DENV antigens and inducible nitric oxide synthase (iNOS in human blood isolated monocytes were analysed by flow cytometry using cells either from patients with acute Dengue Fever or after DENV-1 in vitro infection. DENV-1 susceptibility to iNOS inhibition and NO production was investigated using NG-methyl L-Arginine (NGMLA as an iNOS inhibitor, which was added to DENV-1 infected human monocytes, and sodium nitroprussiate (SNP, a NO donor, added to infected C6/36 mosquito cell clone. Viral antigens after treatments were detected by flow cytometry analysis. Results INOS expression in activated monocytes was observed in 10 out of 21 patients with Dengue Fever and was absent in cells from ten healthy individuals. DENV antigens detected in 25 out of 35 patients, were observed early during in vitro infection (3 days, significantly diminished with time, indicating that virus replicated, however monocytes controlled the infection. On the other hand, the iNOS expression was detected at increasing frequency in in vitro infected monocytes from three to six days, exhibiting an inverse relationship to DENV antigen expression. We demonstrated that the detection of the DENV-1 antigen was enhanced during monocyte treatment with NGMLA. In the mosquito cell line C6/36, virus detection was significantly reduced in the presence of SNP, when compared to that of untreated cells. Conclusion This study is the first to reveal the activation of DENV infected monocytes based on induction of iNOS both in vivo and in vitro, as well as the susceptibility of DENV-1 to a NO production.

  8. JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages

    OpenAIRE

    Eeva Moilanen; Hannu Kankaanranta; Riina Nieminen; Outi Kärpänniemi; Riku Korhonen; Outi Sareila

    2006-01-01

    In inflammation, inducible nitric oxide synthase (iNOS) produces nitric oxide (NO), which modulates inflammatory processes. We investigated the effects of Janus kinase (JAK) inhibitors, AG-490 and WHI-P154, on iNOS expression and NO production in J774 murine macrophages stimulated with interferon-γ (IFN-γ). JAK inhibitors AG-490 and WHI-P154 decreased IFN-γ-induced nuclear levels of signal transducer and activator of transcription 1α (STAT1α). JAK inhibitors AG-490 and WHI-P154 decreased also...

  9. Dogs with patent Dirofilaria immitis infection have higher expression of circulating IL-4, IL-10 and iNOS mRNA than those with occult infection.

    Science.gov (United States)

    Morchón, R; López-Belmonte, J; Bazzocchi, C; Grandi, G; Kramer, L; Simón, F

    2007-01-15

    Dirofilaria immitis is the agent of canine heartworm disease, in which adult worms reside in the pulmonary arteries, producing first stage larvae (microfilariae) that are released into the bloodstream. The present work describes the cytokine and iNOS mRNA expression in the peripheral blood of naturally infected dogs classified as either microfilariemic or amicrofilariemic. Results show that microfilariemic dogs had higher expression of IL-4 and iNOS mRNA than amicrofilariemic dogs. Furthermore, IL-10 mRNA expression was strongly expressed in dogs with circulating microfilariae, compared to only negligible expression in amicrofilariemic dogs. Finally, mf+ status was associated with a predominance in IgG1 production against worm antigens. These results would suggest that circulating mf may stimulate, like in other filarial infections, an immune bias towards unresponsiveness in D. immitis-infected dogs, consenting long-term adult worm survival. PMID:17112598

  10. The gills are an important site of iNOS expression in rainbow trout Oncorhynchus mykiss after challenge with the gram-positive pathogen Renibacterium salmoninarum.

    Science.gov (United States)

    Campos-Perez, J J; Ward, M; Grabowski, P S; Ellis, A E; Secombes, C J

    2000-01-01

    Following injection challenge of rainbow trout with the Gram-positive pathogen Renibacterium salmoninarum, serum nitrate levels increased indicative of NO production. The timing and amount of nitrate produced varied with the virulence of the bacterial strain used, with the highest levels seen in fish challenged with the most virulent (autoaggregating) strain. Immunization with a killed R. salmoninarum preparation in Freund's incomplete adjuvant significantly increased nitrate levels after challenge. Inducible nitric oxide synthase (iNOS) transcript expression was detectable in rainbow trout tissues after injection challenge with R. salmoninarum, and its induction in the gills was both quick (between 3 and 6 hr) and relatively prolonged (lasting several days). iNOS expression in the kidney was also seen at a later stage (24 hr) but appeared to switch off relatively rapidly. Bath challenge with R. salmoninarum also induced iNOS expression in gill, and a variable expression in the gut and kidney also occurred. These results highlight the importance of the gills, not only as a point of entry of pathogens but also as a tissue capable of mounting an immune response. PMID:10651954

  11. The gills are an important site of iNOS expression in rainbow trout Oncorhynchus mykiss after challenge with the Gram‐positive pathogen Renibacterium salmoninarum

    Science.gov (United States)

    Campos‐perez, J J; Ward, M; Grabowski, P S; Ellis, A E; Secombes, C J

    2000-01-01

    Following injection challenge of rainbow trout with the Gram‐positive pathogen Renibacterium salmoninarum, serum nitrate levels increased indicative of NO production. The timing and amount of nitrate produced varied with the virulence of the bacterial strain used, with the highest levels seen in fish challenged with the most virulent (autoaggregating) strain. Immunization with a killed R. salmoninarum preparation in Freund’s incomplete adjuvant significantly increased nitrate levels after challenge. Inducible nitric oxide synthase (iNOS) transcript expression was detectable in rainbow trout tissues after injection challenge with R. salmoninarum, and its induction in the gills was both quick (between 3 and 6 hr) and relatively prolonged (lasting several days). iNOS expression in the kidney was also seen at a later stage (24 hr) but appeared to switch off relatively rapidly. Bath challenge with R. salmoninarum also induced iNOS expression in gill, and a variable expression in the gut and kidney also occurred. These results highlight the importance of the gills, not only as a point of entry of pathogens but also as a tissue capable of mounting an immune response. PMID:10651954

  12. Effect of Radix Paeoniae Rubra on the expression of HO-1 and iNOS in rats with endotoxin-induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    ZHAN Li-ying; XIA Zhong-yuan; CHEN Chang; WANG Xiao-yuan

    2006-01-01

    Objective: To investigate the effect of Radix Paeoniae Rubra (RPR) on the expression of heme oxygenase ( HO-1 ) and induced nitric oxide synthase (iNOS) in endotoxininduced acute lung injury in rats and its protective mechanism.Methods: Forty Wistar rats were divided randomly into 5 groups with 8 rats in each group: saline control group ( NS group ), lipopolysaccharide group ( LPS group), RPR-treatment group, RPR-prevention group and Herin group. The effect of RPR on protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid,malondialdehyde (MDA) content in the lung and the activity of serum NO were observed. Arterial blood was drawn for blood-gas analysis. The expression of HO-1 and iNOS in lung tissues was detected by immunohistochemitry and morphometry computer image analysis. The histological changes of the lung were observed under light microscope.Results: Compared with that in NS group, the expression of HO-1 and iNOS was markedly increased in LPS group (P < 0.01). In RPR-treatment, RPR-prevention, and Hemin groups, the expression of iNOS was significantly lower, while the expression of HO-1 was higher than that in LPS group (P <0.05). The protein content,the ratio of neutrophiles in bronchoalveolar lavage fluid,the content of MDA and the activity of serum NO in LPS group were significantly higher than those in NS group (P < 0.01 ). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in the LPS group (P<0.01); these parameters of lung injury however, were significantly lower in RPR-treatment, RPR-prevention, and Hemin groups than LPS group (P <0.05or P < 0.01). The pathologic changes of lung tissues were substantially attenuated in RPR-treatment, RPR-prevention, and Hemin groups than LPS group.Conclusions : The high expression of HO-1 reflects an important protective function of the body during lipopolysaccharide-induced acute lung injury. The protective effect of RPR on

  13. Evaluation of the anti-inflammatory action of curcumin analog (DM1): Effect on iNOS and COX-2 gene expression and autophagy pathways.

    Science.gov (United States)

    Paulino, Niraldo; Paulino, Amarilis Scremin; Diniz, Susana N; de Mendonça, Sergio; Gonçalves, Ivair D; Faião Flores, Fernanda; Santos, Reginaldo Pereira; Rodrigues, Carina; Pardi, Paulo Celso; Quincoces Suarez, José Agustin

    2016-04-15

    This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375. PMID:27010501

  14. Eupatolide inhibits lipopolysaccharide-induced COX-2 and iNOS expression in RAW264.7 cells by inducing proteasomal degradation of TRAF6.

    Science.gov (United States)

    Lee, Jongkyu; Tae, Nara; Lee, Jung Joon; Kim, Taeho; Lee, Jeong-Hyung

    2010-06-25

    Inula britannica is a traditional medicinal plant used to treat bronchitis, digestive disorders, and inflammation in Eastern Asia. Here, we identified eupatolide, a sesquiterpene lactone from I. britannica, as an inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Eupatolide inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) as well as iNOS and COX-2 protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Eupatolide dose-dependently decreased the mRNA levels and the promoter activities of COX-2 and iNOS in LPS-stimulated RAW264.7 cells. Moreover, eupatolide significantly suppressed the LPS-induced expression of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) reporter genes. Pretreatment of eupatolide inhibited LPS-induced phosphorylation and degradation of I kappaB alpha, and phosphorylation of RelA/p65 on Ser-536 as well as the activation of mitogen-activated protein kinases (MAPKs) and Akt in LPS-stimulated RAW264.7 cells. Eupatolide induced proteasomal degradation of tumor necrosis factor receptor-associated factor-6 (TRAF6), and subsequently inhibited LPS-induced TRAF6 polyubiquitination. These results suggest that eupatolide blocks LPS-induced COX-2 and iNOS expression at the transcriptional level through inhibiting the signaling pathways such as NF-kappaB and MAPKs via proteasomal degradation of TRAF6. Taken together, eupatolide may be a novel anti-inflammatory agent that induces proteasomal degradation of TRAF6, and a valuable compound for modulating inflammatory conditions. PMID:20353767

  15. Inhibitory Effect of Inflexinol on Nitric Oxide Generation and iNOS Expression via Inhibition of NF-κB Activation

    Directory of Open Access Journals (Sweden)

    Jin Tae Hong

    2007-03-01

    Full Text Available Inflexinol, an ent-kaurane diterpenoid, was isolated from the leaves of Isodon excisus. Many diterpenoids isolated from the genus Isodon (Labiatae have antitumor and antiinflammatory activities. We investigated the antiinflammatory effect of inflexinol in RAW 264.7 cells and astrocytes. As a result, we found that inflexinol (1, 5, 10 μM suppressed the expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as the production of nitric oxide (NO in LPS-stimulated RAW 264.7 cells and astrocytes. Consistent with the inhibitory effect on iNOS and COX-2 expression, inflexinol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus. These results suggest that inflexinol inhibits iNOS and COX-2 expression through inhibition of NF-κB activation, thereby inhibits generation of inflammatory mediators in RAW 264.7 cells and astrocytes, and may be useful for treatment of inflammatory diseases.

  16. Investigating the role of tumour cell derived iNOS on tumour growth and vasculature in vivo using a tetracycline regulated expression system.

    Science.gov (United States)

    Papaevangelou, Efthymia; Whitley, Guy S; Johnstone, Alan P; Robinson, Simon P; Howe, Franklyn A

    2016-06-01

    Nitric oxide (NO) is a free radical signalling molecule involved in various physiological and pathological processes, including cancer. Both tumouricidal and tumour promoting effects have been attributed to NO, making its role in cancer biology controversial and unclear. To investigate the specific role of tumour-derived NO in vascular development, C6 glioma cells were genetically modified to include a doxycycline regulated gene expression system that controls the expression of an antisense RNA to inducible nitric oxide synthase (iNOS) to manipulate endogenous iNOS expression. Xenografts of these cells were propagated in the presence or absence of doxycycline. Susceptibility magnetic resonance imaging (MRI), initially with a carbogen (95% O2 /5% CO2 ) breathing challenge and subsequently an intravascular blood pool contrast agent, was used to assess haemodynamic vasculature (ΔR2 *) and fractional blood volume (fBV), and correlated with histopathological assessment of tumour vascular density, maturation and function. Inhibition of NO production in C6 gliomas led to significant growth delay and inhibition of vessel maturation. Parametric fBV maps were used to identify vascularised regions from which the carbogen-induced ΔR2 * was measured and found to be positively correlated with vessel maturation, quantified ex vivo using fluorescence microscopy for endothelial and perivascular cell staining. These data suggest that tumour-derived iNOS is an important mediator of tumour growth and vessel maturation, hence a promising target for anti-vascular cancer therapies. The combination of ΔR2 * response to carbogen and fBV MRI can provide a marker of tumour vessel maturation that could be applied to non-invasively monitor treatment response to iNOS inhibitors. PMID:26756734

  17. LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-κB signaling pathways.

    Science.gov (United States)

    Zhang, Gu; He, Jun-Lin; Xie, Xiao-Yan; Yu, Chao

    2012-09-01

    Activated microglia producing reactive nitrogen species, inflammatory factors, reactive oxygen species (ROS) and other neurovirulent factors, can lead to the development of neurodegenerative diseases. Certain compounds can inhibit the activation of microglia. However, the mechanisms remain unclear. In the present study, we investigated the inhibitory effect of geniposide on the production of ROS and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated N9 murine microglial cells through the p38, ERK1/2 and nuclear factor-κB (NF-κB) signaling pathways. After the N9 cells were pre-treated with the vehicle or geniposide and exposed to LPS for the time indicated, the MTT conversion test was used to assess cell viability. Suitable concentrations were chosen and adjusted according to the experiments. Extracellular nitric oxide (NO) release was measured by Griess reaction. The formation of ROS and intracellular NO was evaluated by fluorescence imaging. NOS activities were determined using commercially available kits. The morphology of the N9 cells was examined by hematoxylin and eosin staining. The expression of iNOS mRNA was examined by RT-PCR. The protein levels of iNOS, p38 mitogen-activated protein kinase (MAPK), ERK1/2 and NF-κB, inhibitory factor-κB-α (IκB-α) were determined by western blot analysis. The results showed that geniposide attenuated the activation of N9 cells and inhibited the overproduction of NO, intracellular ROS and the expression of iNOS induced by LPS in the cells. In addition, geniposide blocked the phosphorylation of p38, ERK1/2 and inhibited the drop-off of IκB induced by LPS in the cells. These data indicate that geniposide has therapeutic potential for the treatment of neurodegenerative diseases, and that it exerts its effects by inhibiting inflammation. PMID:22710392

  18. Effect of Dexamethasone on Nitric Oxide Synthase and Caspase-3 Gene Expressions in Endotoxemia in Neonate Rat Brain

    Institute of Scientific and Technical Information of China (English)

    HUA WANG; YU-BIN WU; XIU-HUA DU

    2005-01-01

    Objective To investigate the gene and protein expressions of three isoforms of nitric oxide synthase (NOS) and gene expression of Caspase-3, and effect of dexamethasone on them in neonatal rats with lipopolysaccharide (LPS)-induced endotoxemic brain damage. Methods Expressions of the three isoforms of NOS and caspase-3 mRNA in the brain were investigated by RT-PCR in postnatal 7-day wistar rats with acute endotoxemia by intraperitoneal administration of LPS. Regional distributions of NOSs were examined by immunohistochemical technique. Results nNOS and Caspase-3 mRNA were obviously detected. eNOS mRNA was faintly expressed, but iNOS mRNA was undetectable in the control rat brain. The expressions of NOS mRNA of three isoforms were weak 2 h after LPS (5 mg/mg) delivery, peaked at 6 h, and thereafter, reduced gradually up to 24 h. The expression intensity was in the order of nNOS> iNOS> eNOS. Widespread nNOS, scattered eNOS distribution and negative iNOS were identified in the control rat brain and all isoforms of NOS could be induced by LPS which reached the apex at 24 h in the order of nNOS> iNOS> eNOS as detected by immunostaining. Although Caspase-3 mRNA could be found in all groups, DNA fragmentation was only seen at 6 h and 24 h. The expressions of NOS and Caspase-3 mRNA were inhibited in the rat brain when dexamethasone was administrated. Conclusion LPS-induced NO production induces apoptosis of neurons through mechanism involving the Caspase-3 activation, which may play an important role in the pathogenesis of brain damage during endotoxemia, and neuro-protective effects of dexamethasone may be partially realized by inhibiting the expression of NOS mRNA.

  19. Selective inhibition of JAK2/STAT1 signaling and iNOS expression mediates the anti-inflammatory effects of coniferyl aldehyde.

    Science.gov (United States)

    Akram, Muhammad; Kim, Kyeong-A; Kim, Eun-Sun; Shin, Young-Jun; Noh, Dabi; Kim, Eunji; Kim, Jeong-Hyeon; Majid, Arshad; Chang, Sun-Young; Kim, Jin-Ki; Bae, Ok-Nam

    2016-08-25

    Urgent needs still exist for selective control of excessive inflammation. Despite the therapeutic potential of natural compounds against inflammation-associated chronic conditions, lack of specific molecular targets renders these bioactive compounds difficult for further development. Here we examined the bioactivity of coniferyl aldehyde (CA), a natural phenolic compound found in several dietary substances and medicinal plants, elucidating its efficacy both in vivo and in vitro with underlying molecular mechanisms. IFN-γ/TNF-α-stimulated human keratinocytes and lipopolysaccharide (LPS)-stimulated murine macrophages were used to examine the effect of CA in vitro and to elucidate the underlying mechanisms. In vivo models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and carrageenan (CRG)-induced paw edema were employed to investigate the topical and systemic anti-inflammatory effects of CA, respectively. CA significantly reduced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated macrophages. While nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways, the representative cellular pathways for iNOS induction, were not affected by CA, phosphorylation of Janus kinase 2 (JAK2) and signal Transducers and Activators of Transcription 1 (STAT1) and subsequent nuclear translocation of p-STAT1 were significantly decreased by CA. The effect of CA on JAK2-STAT1-iNOS axis was also observed in human keratinocytes stimulated with IFN-γ/TNF-α. Topical application of CA to mice produced significant protection against TPA-induced ear edema along with suppressed epidermal hyperproliferation and leucocyte infiltration. Systemic administration of CA significantly reduced CRG-induced paw edema in rats, where CRG-induced iNOS expression and STAT1 phosphorylation were decreased by CA. In summary, CA has significant anti-inflammatory properties both in vitro and in vivo, mediated by

  20. Diphenyleneiodonium inhibits NF-kappaB activation and iNOS expression induced by IL-1beta: involvement of reactive oxygen species

    OpenAIRE

    Mendes, A. Ferreira; Carvalho, A. Pato; Caramona, M. Margarida; Lopes, M. Celeste

    2001-01-01

    AIMS: In this work, we studied the mechanisms by which diphenyleneiodonium chloride (DPI) inhibits nitric oxide (NO) synthesis induced by the proinflammatory cytokine interleukin-1beta (IL-1) in bovine articular chondrocytes. To achieve this, we evaluated the ability of DPI to inhibit the expression and activity of the inducible isoform of the NO synthase (iNOS) induced by IL-1. We also studied the ability of DPI to prevent IL-1-induced NF-kappaB activation and reactive oxygen species (ROS) p...

  1. Diphenyleneiodonium inhibits NF-κB activation and iNOS expression induced by IL-1β: involvement of reactive oxygen species

    OpenAIRE

    A. Ferreira Mendes; A. Pato Carvalho; M. Margarida Caramona; M. Celeste Lopes

    2001-01-01

    Aims: In this work, we studied the mechanisms by which diphenyleneiodonium chloride (DPI) inhibits nitric oxide (NO) synthesis induced by the pro-inflammatory cytokine interleukin-1β (IL-1) in bovine articular chondrocytes. To achieve this, we evaluated the ability of DPI to inhibit the expression and activity of the inducible isoform of the NO synthase (iNOS) induced by IL-1. We also studied the ability of DPI to prevent IL-1-induced NF-κB activation and reactive oxygen species (ROS) product...

  2. Development of Antisense Therapeutic and Imaging Agents to Detect and Suppress Inducible Nitric Oxide Synthase (iNOS) Expression in Acute Lung Injury (ALI)

    Science.gov (United States)

    Shen, Yuefei

    This dissertation focuses on the development and investigation of antisense imaging and therapeutic agents, combined with nanotechnology, to detect and suppress inducible nitric oxide synthase (iNOS) expression for the diagnosis and treatment of acute lung injury (ALI). To achieve this goal, several efforts were made. The first effort was the identification and characterization of high binding affinity antisense peptide nucleic acids (PNAs) and shell-crosslinked knedel-like nanoparticle (SCK)-PNA conjugates to the iNOS mRNA. Antisense binding sites on the iNOS mRNA were first mapped by a procedure for rapidly generating a library of antisense accessible sites on native mRNAs (MASL) which involves reverse transcription of whole cell mRNA extracts with a random oligodeoxynucleotide primer followed by mRNA-specific PCR. Antisense PNAs against the antisense accessible sites were accordingly synthesized and characterized. The second effort was the investigation of cationic shell crosslinked knedel-like nanoparticle (cSCK)-mediated siRNA delivery to suppress iNOS expression for the treatment of ALI. siRNA with its unique gene-specific properties could serve as a promising therapeutic agent, however success in this area has been challenged by a lack of efficient biocompatible transfection agents. cSCK with its nanometer size and positive charge previously showed efficient cellular delivery of phosphorothioate ODNs (oligodeoxynucleotides), plasmid DNA and PNA. Herein, cSCK showed good siRNA binding and facilitated efficient siRNA transfection in HeLa, a mouse macrophage cell line and other human cell lines. cSCK led to greater silencing efficiency than Lipofectamine 2000 in HeLa cells as determined by the viability following transfection with cytotoxic and non-cytotoxic siRNAs, as well in 293T and HEK cells, and was comparable in BEAS-2B and MCF10a cells. The third effort was the preparation of an iNOS imaging probe through electrostatic complexation between a radiolabeled

  3. Atorvastatin Attenuates Bleomycin-Induced Pulmonary Fibrosis via Suppressing iNOS Expression and the CTGF (CCN2/ERK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Bo Zhu

    2013-12-01

    Full Text Available Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-induced lung fibrosis and to further explore the possible underlying mechanisms. Our results showed that atorvastatin administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA level and lung indices. Atorvastatin also markedly decreased the expression of inducible nitric oxide synthase (iNOS in lung tissues and, thus, prevented nitric oxide (NO release in response to bleomycin challenge. Furthermore, atorvastatin exhibited target down-regulation of connective tissue growth factor (CTGF (CCN2 and phosphorylation extracellular regulated protein kinases (p-ERK expression. Taken together, atorvastatin significantly ameliorated bleomycin-induced pulmonary fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2/ERK signaling pathway. The present study provides evidence that atorvastatin may be a potential therapeutic reagent for the treatment of lung fibrosis.

  4. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis.

    Science.gov (United States)

    Camacho-Barquero, Laura; Villegas, Isabel; Sánchez-Calvo, Juan Manuel; Talero, Elena; Sánchez-Fidalgo, Susana; Motilva, Virginia; Alarcón de la Lastra, Catalina

    2007-03-01

    Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro-inflammatory cytokines. Mitogen-activated protein kinases (MAPKs), such as the p38 and the c-Jun N-terminal kinase (JNK) modulate the transcription of many genes involved in the inflammatory process. Curcumin is a polyphenol derived from Curcuma longa, which is known to have anti-inflammatory activity. The aim of this study was to study the effects and mechanisms of action of curcumin, on chronic colitis in rats. Inflammation response was assessed by histology and myeloperoxidase activity (MPO). We determined the production of Th1 and Th2 cytokines and nitrites in colon mucosa, as well as the expression of inducible nitric oxide synthase (iNOS), cyclo-oxygenase(COX)-1 and-2 by western blotting and inmmunohistochemistry. Finally, we studied the involvement of MAPKs signaling in the protective effect of curcumin in chronic colonic inflammation. Curcumin (50-100 mg/kg/day) were administered by oral gavage 24 h after trinitrobenzensulfonic acid (TNBS) instillation, and daily during 2 weeks before sacrifice. Curcumin significantly attenuated the damage and caused substantial reductions of the rise in MPO activity and tumour necrosis factor alpha (TNF)-alpha. Also curcumine was able to reduce nitrites colonic levels and induced down-regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK; however, no changes in the activation of JNK could be observed. In conclusion, we suggest that inhibition of p38 MAPK signaling by curcumin could explain the reduced COX-2 and iNOS immunosignals and the nitrite production in colonic mucosa reducing the development of chronic experimental colitis. PMID:17276891

  5. Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS

    Directory of Open Access Journals (Sweden)

    Aldo Gerbino

    2011-07-01

    Full Text Available Full-term human umbilical cord contains three blood vessels: two arteries coiled around a vein and surrounded by Wharton’s jelly, a mucous tissue with few mesenchymal stromal cells and abundant extracellular matrix. Umbilical vessels lack innervations, thus endothelial cells must play a role in the control of blood flow. The aim of this study was to investigate in human umbilical cord the expression of five peptides that could be involved in the regulation of vascular tone: Orphanin FQ, Oxytocin, Atrial Natriuretic Peptide (ANP, endothelial Nitric Oxide Synthase (eNOS and inducible Nitric Oxide Synthase (iNOS. The expression of these molecules in full-term human umbilical cord was investigated through immunohistochemistry and RT-PCR. Immunoreactivity for Orphanin FQ was detected in Wharton’s jelly, vessel musculature and endothelium; Oxytocin, ANP and eNOS were expressed by the umbilical epithelium, Wharton’s jelly and endothelium, whereas iNOS only by endothelial cells. RT-PCR analysis showed transcriptional expression of Oxytocin, ANP and eNOS mRNAs. The presence of Orphanin, Oxytocin, ANP, eNOS and iNOS proteins was identified in the human umbilical cord. mRNA expression for Oxytocin, ANP and eNOS suggest that these molecules are synthesized by umbilical cord cells themselves. The expression of these vasoactive molecules could be part of a general mechanism locally regulating vascular tone. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 211–218

  6. 8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down-regulating LPS-induced activity of NF-κB and C/EBPβ in Raw 264.7 cells

    International Nuclear Information System (INIS)

    In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, 8-hydroxyquinoline (8HQ) inhibited the LPS-induced expression of both iNOS protein and mRNA in a parallel dose-dependent manner. 8HQ did not enhance the degradation of iNOS mRNA. To investigate the mechanism by which 8HQ inhibits iNOS gene expression, we examined the activation of MAP kinases in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between LPS alone and LPS plus 8HQ-treated cells. Moreover, 8HQ significantly inhibited the DNA-binding activity of nuclear factor-κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), but not activator protein-1 and cAMP response element-binding protein. Taken together, these results suggest that 8HQ acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of C/EBPβ DNA-binding activity and NF-κB activation

  7. N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) suppresses microglial inducible nitric oxide synthase (iNOS) expression and activity induced by interferon-γ (IFN-γ)

    OpenAIRE

    Platten, Michael; Wick, Wolfgang; Wischhusen, Jörg; WELLER, MICHAEL

    2001-01-01

    Microglial cells up-regulate inducible nitric oxide synthase (iNOS) expression in response to various pro-inflammatory stimuli including interferon-γ (IFN-γ), allowing for the release of nitric oxide (NO). Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an antiallergic compound with suppressive effects on the activation of monocytes.Here, we show that N9 murine microglial cells express iNOS mRNA and protein and release nitric oxide into the culture medium in response to IFN-γ (200 ...

  8. Halicephalobus gingivalis (H.deletrix in the brain of a horse Halicephalobus gingivalis (H.deletrix no cérebro de um eqüino

    Directory of Open Access Journals (Sweden)

    Rosemeri de Oliveira Vasconcelos

    2007-08-01

    Full Text Available A 10-year-old Mangalarga gelding with rhabditiform nematode infection in the brain is described. Clinical signs were limited to circling and right side paralysis. Histological examination of the brain revealed marked gliosis and discreet edema. The perivascular mononuclear inflammatory infiltrate was composed of few layers of lymphocytes, plasmocytes and macrophages and rare eosinophils. The presence of rhabditiform nematodes was associated with the infiltrate. Areas of malacia associated with the parasites and parasite tracks with axonal spheroids were also seen close to the vessels and to the etiological agent and were more evident in the white matter. In the meninges there was moderate inflammatory infiltrate associated with perivascular parasites. The identification of the nematode was based on the histological examination of the cerebral fragments.Um eqüino macho, com 10 anos, Mangalarga, apresentou uma infecção por um nematódeo rabditiforme no cérebro. Os sinais clínicos limitaram-se ao fato de o animal andar em círculos e apresentar paralisia do lado direito. O exame histológico do cérebro revelou acentuada gliose e discreto edema intersticial. O infiltrado inflamatório mononuclear perivascular era composto por poucas camadas de linfócitos, plasmócitos, macrófagos e raros eosinófilos, associados aos nematódeos rabditiformes. Áreas de malácia e trajetos com esferóides axonais são vistos ao redor de vasos e do agente etiológico, sendo mais evidentes na substância branca. Nas meninges, o infiltrado inflamatório foi moderado e associado a parasitas perivasculares. A identificação do nematódeo foi baseada no exame histológico do cérebro do cavalo.

  9. Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jiapeng YANG

    2016-01-01

    Full Text Available Background and objective Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB-inducible nitric oxide synthase (iNOS signaling pathway of lung tissue in Xuanwei lung cancer patients. Methods From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. Results A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si content was found in inorganic elemental analysis. The serum interleukin (IL-1β levels (31.50±19.16 pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33±6.94 pg/mL (P<0.01, with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung

  10. Comparison of inducible nitric oxide synthase expression in the brains of Listeria monocytogenes-infected cattle, sheep, and goats and in macrophages stimulated in vitro.

    OpenAIRE

    Jungi, T. W.; Pfister, H.; Sager, H.; Fatzer, R.; Vandevelde, M; Zurbriggen, A

    1997-01-01

    The expression of inducible nitric oxide synthase (iNOS) was studied in the brains of cattle, sheep, and goat that succumbed to a natural infection with Listeria monocytogenes. The lesions in infected brains are characterized by microabscesses, perivascular cuffs, gliosis, glial nodules, and large areas of malacia. Using immunocytochemistry, we detected bacteria in microabscesses, particularly in sheep and goats, and in areas without signs of inflammation, but not in perivascular infiltrates....

  11. Acclimation-dependent expression of heat shock protein 70 in Pacific abalone (Haliotis discus hannai Ino) and its acute response to thermal exposure

    Institute of Scientific and Technical Information of China (English)

    LI Jiaqi; HE Qingguo; SUN Hui; LIU Xiao

    2012-01-01

    Heat shock protein 70 (Hsp70) is one important member of heat shock protein (Hsp) family that is responsible for various stresses,especially thermal stress.Here we examined the response of Hsp70gene to both chronic and acute thermal exposure in Pacific abalone (Haliotis discus hannai Ino).For the chronic exposure,abalones were maintained at 8,12,20,and 30℃ for four months and their mRNA levels were measured.The highest mRNA level of Hsp70 gene relative to actin gene was detected in the 30℃-acclimated group,followed by the 8℃-acclimated group and then the 12℃- and 20℃-acclimated groups.After the long-term acclimation,gills from each of the above acclimation groups were dissected and exposed to different temperatures between 8℃ and 38℃ for 30 min.Hsp70 expression in gills acclimated to different temperatures responded differentially to the same temperature exposure.The incubation temperature that induced maximum Hsp70 mRNA expression was higher in the higher temperature acclimation groups than lower temperature groups.Pacific abalones could alter the expression pattern of Hsp70 gene according to environmental thermal conditions,through which they deal with the stress of thermal variations.

  12. CXCL12 expression in hematopoietic tissues of mice exposed to sublethal dose of ionizing radiation in the presence od iNOS inhibitor

    International Nuclear Information System (INIS)

    Full text of publication follows: We study the production of CXCL12, a stem cell homing chemokine, in spleen and bone marrow of mice exposed at LD50% of γ-radiation, w/wo a iNOS blocker, aminoguanidine, to test if inflammatory nitric oxide is involved in necrotic processes of stem cell death after ionizing radiation exposure. Groups of 10 male 6-week old C57Bl/6j mice were killed at specific time points after a 8Gy dose irradiation (60Co source; 4,22kGy/h dose rate) and spleen and bone marrow samples were immersed and stored in TriZOL for total mRNA extraction. RT-PCR assays were performed to determine the production of CXCL12 as compared to murine β-actin at days 2nd, 5th, 7th, 9th and 15th days after radiation in a semiquantitative way. PCR was performed after cDNA synthesis using Oligo-dT primers and specific primers for CXCL12 and β-actin. Artificial optical density was determined in silver-stained PAGE resolved specific amplification products of CXCL12, using amplification of murine β-actin as standard, and measurements obtained by the Image J freeware. CXCL12 production in spleen samples reached its maximum at 5th day after radiation exposure in animals not treated with aminoguanidine, but this peak was extended to at 7th day in treated animals. Non treated animals presented a decrease of CXCL12 expression up to 15th day of experiment, and aminoguanidine treated animals showed sustained increase of expression levels between 9th and 15th days. In bone marrow samples, the main difference among the two different experimental groups was a maintenance of CXCL12 mRNA expression between 7th and 9th days, persisting until the end of the experiment. Our data demonstrates that the effect of aminoguanidine appears to sustain the CXCL12 mRNA synthesis in hematopoietic tissues of irradiated mice, providing some evidences that the axis iNOS -NO - inflammation must be involved in stem cell death, aside to the direct radiation effect, suggesting their use associated to

  13. The human parasite Leishmania amazonensis downregulates iNOS expression via NF-κB p50/p50 homodimer: role of the PI3K/Akt pathway

    Science.gov (United States)

    Calegari-Silva, Teresa C.; Vivarini, Áislan C.; Miqueline, Marina; Dos Santos, Guilherme R. R. M.; Teixeira, Karina Luiza; Saliba, Alessandra Mattos; Nunes de Carvalho, Simone; de Carvalho, Laís; Lopes, Ulisses G.

    2015-01-01

    Leishmania amazonensis activates the NF-κB transcriptional repressor homodimer (p50/p50) and promotes nitric oxide synthase (iNOS) downregulation. We investigated the role of PI3K/Akt in p50/p50 NF-κB activation and the effect on iNOS expression in L. amazonensis infection. The increased occupancy of p50/p50 on the iNOS promoter of infected macrophages was observed and we demonstrated that both p50/p50 NF-κB induction and iNOS downregulation in infected macrophages depended on PI3K/Akt activation. Importantly, the intracellular growth of the parasite was also impaired during PI3K/Akt signalling inhibition and in macrophages knocked-down for Akt 1 expression. It was also observed that the increased nuclear levels of p50/p50 in L. amazonensis-infected macrophages were associated with reduced phosphorylation of 907 Ser p105, the precursor of p50. Corroborating these data, we demonstrated the increased levels of phospho-9 Ser GSK3β in infected macrophages, which is associated with GSK3β inhibition and, consequently, its inability to phosphorylate p105. Remarkably, we found that the levels of pPTEN 370 Ser, a negative regulator of PI3K, increased due to L. amazonensis infection. Our data support the notion that PI3K/Akt activity is sustained during the parasite infection, leading to NF-κB 105 phosphorylation and further processing to originate p50/p50 homodimers and the consequent downregulation of iNOS expression. PMID:26400473

  14. Assessment of the effect of diode laser therapy on incisional wound healing and expression of iNOS and eNOS on rat oral tissue

    Directory of Open Access Journals (Sweden)

    Parichehr Ghalayani

    2013-01-01

    Conclusion: Histological findings showed that diode laser needs several repeated irradiations for the acceleration of wound healing. The iNOS amount showed that increases are associated with better healing.

  15. Expression of inflammation related factors iNOS and ICAM-1 in endothelial cells induced by C-reactive protein

    OpenAIRE

    Song, Xu-Dong; Chen, Ai-Hua; He, Fei; Li, Zhi-Liang; Ying-feng LIU

    2011-01-01

    Objective To investigate the expression of inducible nitric oxide synthase(iNOS) and intercellular cell adhesion molecule-1(ICAM-1) in endothelial cells induced by C-reactive protein(CRP) and its corresponding mechanisms.Methods Human umbilical cord vein endothelial cells(HUVEC) were treated with different concentrations of CRP or with phosphate buffered solution as control,and RT-PCR was used for measurement of the expression of ICAM-1 mRNA induced by CRP in HUVECs.HUVEC were treated with CR...

  16. The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

    Directory of Open Access Journals (Sweden)

    Chandra M Ohri

    Full Text Available BACKGROUND: We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM expression of proteins associated with M1 and M2 macrophages in NSCLC. METHODS: Using immunohistochemistry, CD68(+ macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14, or a non-cytotoxic M2 phenotype (CD163 and VEGF were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES (median 92.7 months and 20 patients with poor survival (PS (median 7.7 months. RESULTS: The NM expression of NM-HLA-DR (p<0.001, NM-iNOS (p = 0.02 and NM-MRP 8/14 (p = 0.02 was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001. There was more NM-CD163 expression (p = 0.04 but less NM-iNOS (p = 0.002 and MRP 8/14 (p = 0.01 expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001, 65.0% versus 14.6% (NM-iNOS p = 0.003, and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04, as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41 and 19.4% versus 59.0% (NM-VEGF p = 0.001. CONCLUSIONS: Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

  17. Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration

    Directory of Open Access Journals (Sweden)

    Brown Guy C

    2005-09-01

    Full Text Available Abstract Background Inflammation-activated glia are seen in many CNS pathologies and may kill neurons through the release of cytotoxic mediators, such as nitric oxide from inducible NO synthase (iNOS, and possibly superoxide from NADPH oxidase (NOX. We set out to determine the relative role of these species in inducing neuronal death, and to test the dual-key hypothesis that the production of both species simultaneously is required for significant neuronal death. Methods Primary co-cultures of cerebellar granule neurons and glia from rats were used to investigate the effect of NO (from iNOS, following lipopolysaccharide (LPS and/or cytokine addition or superoxide/hydrogen peroxide (from NOX, following phorbol 12-myristate 13-acetate (PMA, ATP analogue (BzATP, interleukin-1β (IL-1β or arachidonic acid (AA addition on neuronal survival. Results Induction of glial iNOS caused little neuronal death. Similarly, activation of NOX alone resulted in little or no neuronal death. However, if NOX was activated (by PMA or BzATP in the presence of iNOS (induced by LPS and interferon-γ then substantial delayed neuronal death occurred over 48 hours, which was prevented by inhibitors of iNOS (1400W, NOX (apocynin or a peroxynitrite decomposer (FeTPPS. Neurons and glia were also found to stain positive for nitrotyrosine (a putative marker of peroxynitrite only when both iNOS and NOX were simultaneously active. If NOX was activated by weak stimulators (IL-1β, AA or the fibrillogenic prion peptide PrP106-126 in the presence of iNOS, it caused microglial proliferation and delayed neurodegeneration over 6 days, which was prevented by iNOS or NOX inhibitors, a peroxynitrite decomposer or a NMDA-receptor antagonist (MK-801. Conclusion These results suggest a dual-key mechanism, whereby glial iNOS or microglial NOX activation alone is relatively benign, but if activated simultaneously are synergistic in killing neurons, through generating peroxynitrite. This

  18. Dietary ascorbic acid modulates the expression profile of stress protein genes in hepatopancreas of adult Pacific abalone Haliotis discus hannai Ino.

    Science.gov (United States)

    Wu, Chenglong; Wang, Jia; Xu, Wei; Zhang, Wenbing; Mai, Kangsen

    2014-12-01

    This study was conducted to investigate the effects of dietary ascorbic acid (AA) on transcriptional expression patterns of antioxidant proteins, heat shock proteins (HSP) and nuclear factor kappa B (NF-κB) in the hepatopancreas of Pacific abalone Haliotis discus hannai Ino (initial average length: 84.36 ± 0.24 mm) using real-time quantitative PCR assays. L-ascorbyl-2-molyphosphate (LAMP) was added to the basal diet to formulate four experimental diets containing 0.0, 70.3, 829.8 and 4967.5 mg AA equivalent kg(-1) diets, respectively. Each diet was fed to triplicate groups of adult abalone in acrylic tanks (200 L) in a flow-through seawater system. Each tank was stocked with 15 abalone. Animals were fed once daily (17:00) to apparent satiation for 24 weeks. The results showed that the dietary AA (70.3 mg kg(-1)) could significantly up-regulate the expression levels of Cu/Zn superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), feritin (FT) and heat shock protein 26 (HSP26) in the hepatopancreas of abalone in this treatment compared to the controls. However, the expression levels of Mn-SOD, glutathione peroxidase (GPX), thioredoxin peroxidase (TPx), selenium-binding protein (SEBP), HSP70 and HSP90 were significantly down-regulated. Compared with those in the group with 70.3 mg kg(-1) dietary AA, the expression levels of CAT, GST and HSP26 were decreased in abalone fed with very high dietary AA (4967.5 mg kg(-1)). In addition, significant up-regulations of expression levels of Mn-SOD, GPX, TPx, SEBP, FT, HSP70, HSP90 and NF-κB were observed in abalone fed with apparently excessive dietary AA (829.8 and 4967.5 mg kg(-1)) as compared to those fed 70.3 mg kg(-1) dietary AA. These findings showed that dietary AA influenced the expression levels of antioxidant proteins, heat shock proteins and NF-κB in the hepatopancreas of abalone at transcriptional level. Levels of dietary AA that appeared adequate (70.3 mg kg(-1)) reduced the oxidative stress

  19. Rheosmin, a naturally occurring phenolic compound inhibits LPS-induced iNOS and COX-2 expression in RAW264.7 cells by blocking NF-kappaB activation pathway.

    Science.gov (United States)

    Jeong, Jin Boo; Jeong, Hyung Jin

    2010-01-01

    Inflammation is part of the host defense mechanism against harmful matters and injury; however, aberrant inflammation is associated to the development of chronic disease such as cancer. Raspberry ketone is a natural phenolic compound. It is used in perfumery, in cosmetics, and as a food additive to impart a fruity odor. In this study, we evaluated whether rheosmin, a phenolic compound isolated from pine needles regulates the expression of iNOS and COX-2 protein in LPS-stimulated RAW264.7 cells. Rheosmin dose-dependently inhibited NO and PGE(2) production and also blocked LPS-induced iNOS and COX-2 expression. Rheosmin potently inhibited the translocation of NF-kappaB p65 into the nucleus by IkappaB degradation following IkappaB-alpha phosphorylation. This result shows that rheosmin inhibits NF-kappaB activation. In conclusion, our results suggest that rheosmin inhibits LPS-induced iNOS and COX-2 expression in RAW264.7 cells by blocking NF-kappaB activation pathway. PMID:20478352

  20. Gene expression in the Parkinson's disease brain

    OpenAIRE

    Lewis, Patrick A.; Cookson, Mark R.

    2012-01-01

    The study of gene expression has undergone a transformation in the past decade as the benefits of the sequencing of the human genome have made themselves felt. Increasingly, genome wide approaches are being applied to the analysis of gene expression in human disease as a route to understanding the underlying pathogenic mechanisms. In this review, we will summarise current state of gene expression studies of the brain in Parkinson's disease, and examine how these techniques can be used to gain...

  1. Disturbance effects of PM₁₀ on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia-reperfusion injury in isolated rat heart: protective role of vanillic acid.

    Science.gov (United States)

    Dianat, Mahin; Radmanesh, Esmat; Badavi, Mohammad; Mard, Seyed Ali; Goudarzi, Gholamraza

    2016-03-01

    Myocardial infarction is the acute condition of myocardial necrosis that occurs as a result of imbalance between coronary blood supply and myocardial demand. Air pollution increases the risk of death from cardiovascular diseases (CVDs). The aim of this study was to investigate the effects of particulate matter (PM) on oxidative stress, the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) level induced by ischemia-reperfusion injury, and the protective effects of vanillic acid (VA) in the isolated rat heart. Male Wistar rats were randomly divided into eight groups (n = 10), namely control, VAc, sham, VA, PMa (0.5 mg/kg), PMb (2.5 mg/kg), PMc (5 mg/kg), and PMc + VA groups. Particles with an aerodynamic diameter lactate dehydrogenase (LDH) were measured using special kits. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine levels of iNOS and eNOS mRNA. An increase in left ventricular end-diastolic pressure (LVEDP), S-T elevation, and oxidative stress in PM10 groups was observed. Ischemia-reperfusion (I/R) induction showed a significant augment in the expression of iNOS mRNA level and a significant decrease in the expression eNOS mRNA level. This effect was more pronounced in the PM groups than in the control and sham groups. Vanillic acid caused a significant decrease in LVEDP, S-T elevation, and also a significant difference in eNOS mRNA expression level, antioxidant enzymes, iNOS mRNA expression level, and oxidative stress occurred on myocardial dysfunction after I/R in isolated rat hearts. This study showed that PM10 exposure had devastating effects on the myocardial heart, oxidative stress, and eNOS and iNOS mRNA expression levels. Vanillic acid was able to improve these parameters. Vanillic acid as a potent antioxidant could also provide protection against particulate matter-induced toxicity. PMID:26552794

  2. Anti-Inflammatory Effects of Flavonoids: Genistein, Kaempferol, Quercetin, and Daidzein Inhibit STAT-1 and NF-κB Activations, Whereas Flavone, Isorhamnetin, Naringenin, and Pelargonidin Inhibit only NF-κB Activation along with Their Inhibitory Effect on iNOS Expression and NO Production in Activated Macrophages

    Directory of Open Access Journals (Sweden)

    Mari Hämäläinen

    2007-01-01

    The present study characterises the effects and mechanisms of naturally occurring phenolic compounds on iNOS expression and NO production in activated macrophages. The results partially explain the pharmacological efficacy of flavonoids as anti-inflammatory compounds.

  3. Multi-walled carbon nanotubes induce COX-2 and iNOS expression via MAP Kinase-dependent and -independent mechanisms in mouse RAW264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Lee Jong

    2012-05-01

    Full Text Available Abstract Background Carbon nanotubes (CNTs are engineered graphene cylinders with numerous applications in engineering, electronics and medicine. However, CNTs cause inflammation and fibrosis in the rodent lung, suggesting a potential human health risk. We hypothesized that multi-walled CNTs (MWCNTs induce two key inflammatory enzymes in macrophages, cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS, through activation of extracellular signal-regulated kinases (ERK1,2. Methods RAW264.7 macrophages were exposed to MWCNTs or carbon black nanoparticles (CBNPs over a range of doses and time course. Uptake and subcellular localization of MWCNTs was visualized by transmission electron microscopy (TEM. Protein levels of COX-2, iNOS, and ERK1,2 (total ERK and phosphorylated ERK were measured by Western blot analysis. Prostaglandin-E2 (PGE2 and nitric oxide (NO levels in cell supernatants were measured by ELISA and Greiss assay, respectively. Results MWCNTs, but not CBNPs, induced COX-2 and iNOS in a time- and dose-dependent manner. COX-2 and iNOS induction by MWCNTs correlated with increased PGE2 and NO production, respectively. MWCNTs caused ERK1,2 activation and inhibition of ERK1,2 (U0126 blocked MWCNT induction of COX-2 and PGE2 production, but did not reduce the induction of iNOS. Inhibition of iNOS (L-NAME did not affect ERK1,2 activation, nor did L-NAME significantly decrease COX-2 induction by MWCNT. Nickel nanoparticles (NiNPs, which are present in MWCNTs as a residual catalyst, also induced COX-2 via ERK-1,2. However, a comparison of COX-2 induction by MWCNTs containing 4.5 and 1.8% Ni did not show a significant difference in ability to induce COX-2, indicating that characteristics of MWCNTs in addition to Ni content contribute to COX-2 induction. Conclusion This study identifies COX-2 and subsequent PGE2 production, along with iNOS induction and NO production, as inflammatory mediators involved in the macrophage response to

  4. Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages.

    Science.gov (United States)

    Yeh, J L; Hsu, J H; Hong, Y S; Wu, J R; Liang, J C; Wu, B N; Chen, I J; Liou, S F

    2011-01-01

    Eugenol and isoeugenol, two components of clover oil, have been reported to possess several biomedical properties, such as anti-inflammatory, antimicrobial and antioxidant effects. This study aims to examine the anti-inflammatory effects of eugenol, isoeugenol and four of their derivatives on expression of inducible nitric oxide synthase (iNOS) activated by lipopolysaccharide (LPS) in mouse macrophages (RAW 264.7), and to investigate molecular mechanisms underlying these effects. We found that two derivatives, eugenolol and glyceryl-isoeugenol, had potent inhibitory effects on LPS-induced upregulation of nitrite levels, iNOS protein and iNOS mRNA. In addition, they both suppressed the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) induced by LPS. Moreover, they both attenuated the DNA binding of NF-kB and AP-1, phosphorylation of inhibitory kB-alpha (IkB-alpha), and nuclear translocation of p65 protein induced by LPS. Finally, we demonstrated that glyceryl-isoeugenol suppressed the phosphorylation of ERK1/2, JNK and p38 MAPK, whereas eugenolol suppressed the phosphorylation of ERK1/2 and p38 MAPK. Taken together, these results suggest that that eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kB and AP-1 through inhibition of MAPKs and Akt/IkB-alpha signaling pathways. Thus, this study implies that eugenolol and glyceryl-isoeugenol may provide therapeutic benefits for inflammatory diseases. PMID:21658309

  5. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  6. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  7. iNOS signaling interacts with COX-2 pathway in colonic fibroblasts.

    Science.gov (United States)

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-10-01

    COX-2 and iNOS are two major inflammatory mediators implicated in colorectal inflammation and cancer. Previously, the role of colorectal fibroblasts involved in regulation of COX-2 and iNOS expression was largely ignored. In addition, the combined interaction of COX-2 and iNOS signalings and their significance in the progression of colorectal inflammation and cancer within the fibroblasts have received little investigation. To address those issues, we investigated the role of colonic fibroblasts in the regulation of COX-2 and iNOS gene expression, and explored possible mechanisms of interaction between COX-2 and iNOS signalings using a colonic CCD-18Co fibroblast line and LPS, a potential stimulator of COX-2 and iNOS. Our results clearly demonstrated that LPS activated COX-2 gene expression and enhanced PGE(2) production, stimulated iNOS gene expression and promoted NO production in the fibroblasts. Interestingly, activation of COX-2 signaling by LPS was not involved in activation of iNOS signaling, while activation of iNOS signaling by LPS contributed in part to activation of COX-2 signaling. Further analysis indicated that PKC plays a major role in the activation and interaction of COX-2 and iNOS signalings induced by LPS in the fibroblasts. PMID:22683859

  8. IL-1beta-Induced iNOS Expression, NO Release and Loss in Metabolic Cell Viability Are Resistant to Inhibitors of Ceramide Synthase and Sphingomyelinase in INS 832/13 Cells

    Directory of Open Access Journals (Sweden)

    Rajakrishnan Veluthakal

    2006-11-01

    Full Text Available Context Emerging evidence indicates regulatory roles for ceramide in the metabolic dysfunction of the islet beta cell. Recently, potential similarities between IL-1beta and ceramide on their effects on islet beta cell have been reported, including reduction in mitochondrial membrane potential and loss in metabolic cell viability.Objective Herein, we investigated whether IL-1beta-induced nitric oxide synthetase (iNOS expression, nitric oxide (NO release and loss in metabolic cell viability require ceramide biosynthesis either via the activation of sphingomyelinase or ceramide synthase.Setting Insulin-secreting INS 832/13 cells.Results We found that two structurally-distinct inhibitors of sphingomyelinase activation (e.g., 3-O-methylsphingomyelin or desipramine or ceramide biosynthesis inhib-itor (e.g., fumonisin failed to exert clear effects on IL-1beta-induced iNOS expression, NO release and loss in cell viability.Conclusions Taken together, our findings indicate that neither the sphingomyelinase nor the ceramide synthase activation is required for IL-1beta-induced metabolic abnormalities in insulin-secreting INS 832/13 cells.

  9. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette;

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed in...... the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other...

  10. Aquaporin-11 (AQP11) Expression in the Mouse Brain

    OpenAIRE

    Shin Koike; Yasuko Tanaka; Toshiyuki Matsuzaki; Yoshiyuki Morishita; Kenichi Ishibashi

    2016-01-01

    Aquaporin-11 (AQP11) is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA) and protein were expressed in the brain, but much less than in the thymus and kidn...

  11. Location and Quantification of iNOS in Testis of Dahl Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    Jing LIU; Rui-li LI; Huan-Ying ZHAO; Xiu-Ling YIN

    2004-01-01

    Objective To study the effect of hypertension on inducible isoform of nitrogen oxide syntheses (iNOS) expression and reproductive function in testes of Dahl hypertensive rats Method The iNOS expression in Dahl rat testes was localized and assayed semi-quan titatively by immunohistochemistry.Results iNOS was expressed and localized predominantly in the cytoplasm of Sertoli and Leydig cells in both normal and hypertensive rats. However, in the early stage of hypertension, the expression of iNOS was stronger in testes than that of the normal rats (P<0. 05). With the development, the staining intensity of iNOS decreased gradually in the late stage. Moreover, the level of testosterone decreased with the increase of blood pressure. But in vitro, there was no difference in the expression of iNOS between cultured Sertoli cells from normal rats and hypertensive rats.Conclusion High-salt food induced hypertension in Dahl rats, which was characterized by the high expression of iNOS in rat Sertoli and Leydig cells; excessive NO produced by iNOS reduced the level of testosterone in testicle artery, and may thus affect the reproductive function of rats testis.

  12. Methodological Considerations For Gene Expression Profiling Of Human Brain

    OpenAIRE

    Atz, Mary; Walsh, David; Cartagena, Preston; Li, Jun; Evans, Simon; Choudary, Prabhakara; Overman, Kevin; Stein, Richard; Tomita, Hiro; Potkin, Steven; Myers, Rick; Watson, Stanley J.; Jones, E G; Akil, Huda; Bunney, William E.

    2007-01-01

    Gene expression profiles of postmortem brain tissue represent important resources for understanding neuropsychiatric illnesses. The impact(s) of quality covariables on the analysis and results of gene expression studies are important questions. This paper addressed critical variables which might affect gene expression in two brain regions. Four broad groups of quality indicators in gene expression profiling studies (clinical, tissue, RNA, and microarray quality) were identified. These quality...

  13. An anatomic gene expression atlas of the adult mouse brain

    OpenAIRE

    Ng, Lydia; Bernard, Amy; Lau, Chris; Overly, Caroline C.; Dong, Hong-Wei; Kuan, Chihchau; Pathak, Sayan; Sunkin, Susan M.; Dang, Chinh; Bohland, Jason W.; Bokil, Hemant; Mitra, Partha P.; Puelles, Luis; Hohmann, John; Anderson, David J.

    2009-01-01

    Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of gene...

  14. MicroRNA expression profiles and functions in the brain

    Institute of Scientific and Technical Information of China (English)

    Yanting Qi; Yu Zhao; Zhuyin Chen; Xiaona Chen; Marie C. Lin; Xiangfu Kong; Lihui Lai

    2008-01-01

    MicroRNAs are abundant in the brains of vertebrates and some show a brain-specific or brain-enriched expression pattern. Because microRNAs regulate the expression of hundreds of target genes, it is not surprising that they have profoundly important functions in brain development and pathological processes. For example, miR-124 plays an important role in inducing and maintaining neuronal identity through targeting at least two anti-neural factors. MicroRNAs have also been implicated in brain disorders, including brain tumors and neurodegenerative diseases. This review aims to present an overview of the expression profiles and functions of microRNAs in the developing brains of vertebrates.

  15. Expression of iron-related genes in human brain and brain tumors

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  16. Gene Expression Profiling in the Brains of Human Cocaine Abusers

    OpenAIRE

    Bannon, Michael J.; Kapatos, Gregory; ALBERTSON, DAWN N.

    2005-01-01

    Chronic cocaine abuse induces long-term neurochemical, structural and behavioural changes thought to result from altered gene expression within the nucleus accumbens and other brain regions playing a critical role in addiction. Recent methodological advances now allow the profiling of gene expression in human postmortem brain. In this article, we review studies in which we have used Affymetrix oligonucleotide microarrays to identify transcripts that are differentially expressed in the nucleus...

  17. MicroRNA Expression Profiling of the Porcine Developing Brain

    DEFF Research Database (Denmark)

    Podolska, Agnieszka; Kaczkowski, Bogumil; Busk, Peter Kamp; Søkilde, Rolf; Litman, Thomas; Fredholm, Merete; Cirera, Susanna

    2011-01-01

    MicroRNAs are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level and play an important role in the control of developmental and physiological processes. In particular, the developing brain contains an impressive diversity of microRNAs. Most microRNA...... the growth curve when compared to humans. Considering these similarities, studies examining microRNA expression during porcine brain development could potentially be used to predict the expression profile and role of microRNAs in the human brain....

  18. Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

    Directory of Open Access Journals (Sweden)

    Saldanha Colin J

    2011-07-01

    Full Text Available Abstract Background Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown. Methods Adult male zebra finches (Taeniopygia guttata were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA, an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test. Results Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression. Conclusions These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

  19. Neuroglobin and Cytoglobin expression in the human brain

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Kelsen, Jesper; Hay-Schmidt, Anders

    2013-01-01

    Neuroglobin and Cytoglobin are new members of the heme-globin family. Both globins are primarily expressed in neurons of the brain and retina. Neuroglobin and Cytoglobin have been suggested as novel therapeutic targets in various neurodegenerative diseases based on their oxygen binding and cell...... protecting properties. However, findings in Neuroglobin-deficient mice question the endogenous neuroprotective properties. The expression pattern of Neuroglobin and Cytoglobin in the rodent brain is also in contradiction to a major role of neuronal protection. In a recent study, Neuroglobin was ubiquitously...... expressed and up-regulated following stroke in the human brain. The present study aimed at confirming our previous observations in rodents using two post-mortem human brains. The anatomical localization of Neuroglobin and Cytoglobin in the human brain is much like what has been described for the rodent...

  20. CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Chan [Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Hyun Joo, So [Department of Pharmacology, School of Medicine, Konkuk University (Korea, Republic of); Shin, Chan Young, E-mail: chanyshin@kku.ac.kr [Department of Pharmacology, School of Medicine, Konkuk University (Korea, Republic of)

    2011-06-17

    Highlights: {yields} Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. {yields} JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. {yields} Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. {yields} CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.

  1. CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

    International Nuclear Information System (INIS)

    Highlights: → Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. → JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. → Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. → CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.

  2. Metal ion toxins and brain aquaporin-4 expression: an overview

    Directory of Open Access Journals (Sweden)

    Adriana eXimenes-Da-Silva

    2016-06-01

    Full Text Available Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS results in changes in blood-brain barrier (BBB permeability, as well as triggering microglia activation and astrocyte reactivity and changing water transport through the cells, which could result in brain swelling. Aquaporin-4 is the main water channel in the CNS, is expressed in astrocyte foot processes in brain capillaries and along the circumventricular epithelium in the ventricles, and has important physiological functions in maintaining brain osmotic homeostasis and supporting brain excitability through regulation of the extracellular space. Some evidence has pointed to a role of AQP4 during metal intoxication in the brain, where it may act in a dual form as a neuroprotector or a mediator of the development of oxidative stress in neurons and astrocytes, resulting in brain swelling and neuronal damage. This mini-review presents the way some metal ions affect changes in AQP4 expression in the CNS and discuss the ways in which water transport in brain cells can be involved in brain damage.

  3. Metal Ion Toxins and Brain Aquaporin-4 Expression: An Overview.

    Science.gov (United States)

    Ximenes-da-Silva, Adriana

    2016-01-01

    Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS) results in changes in blood-brain barrier (BBB) permeability, as well as triggering microglia activation and astrocyte reactivity and changing water transport through the cells, which could result in brain swelling. Aquaporin-4 is the main water channel in the CNS, is expressed in astrocyte foot processes in brain capillaries and along the circumventricular epithelium in the ventricles, and has important physiological functions in maintaining brain osmotic homeostasis and supporting brain excitability through regulation of the extracellular space. Some evidence has pointed to a role of AQP4 during metal intoxication in the brain, where it may act in a dual form as a neuroprotector or a mediator of the development of oxidative stress in neurons and astrocytes, resulting in brain swelling and neuronal damage. This mini-review presents the way some metal ions affect changes in AQP4 expression in the CNS and discuss the ways in which water transport in brain cells can be involved in brain damage. PMID:27313504

  4. MicroRNA expression profiling of the porcine developing brain.

    Directory of Open Access Journals (Sweden)

    Agnieszka Podolska

    Full Text Available BACKGROUND: MicroRNAs are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level and play an important role in the control of developmental and physiological processes. In particular, the developing brain contains an impressive diversity of microRNAs. Most microRNA expression profiling studies have been performed in human or rodents and relatively limited knowledge exists in other mammalian species. The domestic pig is considered to be an excellent, alternate, large mammal model for human-related neurological studies, due to its similarity in both brain development and the growth curve when compared to humans. Considering these similarities, studies examining microRNA expression during porcine brain development could potentially be used to predict the expression profile and role of microRNAs in the human brain. METHODOLOGY/PRINCIPAL FINDINGS: MicroRNA expression profiling by use of microRNA microarrays and qPCR was performed on the porcine developing brain. Our results show that microRNA expression is regulated in a developmentally stage-specific, as well as a tissue-specific manner. Numerous developmental stage or tissue-specific microRNAs including, miR-17, miR-18a, miR-29c, miR-106a, miR-135a and b, miR-221 and miR-222 were found by microarray analysis. Expression profiles of selected candidates were confirmed by qPCR. CONCLUSIONS/SIGNIFICANCE: The differential expression of specific microRNAs in fetal versus postnatal samples suggests that they likely play an important role in the regulation of developmental and physiological processes during brain development. The data presented here supports the notion that microRNAs act as post-transcriptional switches which may regulate gene expression when required.

  5. TSPO expression in brain tumours:is TSPO a target for brain tumour imaging?

    OpenAIRE

    Roncaroli, Federico; Su, Zhangjie; Herholz, Karl; Gerhard, Alexander; Turkheimer, Federico E.

    2016-01-01

    Positron emission tomography (PET) alone or in combination with MRI is increasingly assuming a central role in the development of diagnostic and therapeutic strategies for brain tumours with the aim of addressing tumour heterogeneity, assisting in patient stratification, and contributing to predicting treatment response. The 18 kDa translocator protein (TSPO) is expressed in high-grade gliomas, while its expression is comparatively low in normal brain. In addition, the evidence of elevated TS...

  6. An anatomic gene expression atlas of the adult mouse brain.

    Science.gov (United States)

    Ng, Lydia; Bernard, Amy; Lau, Chris; Overly, Caroline C; Dong, Hong-Wei; Kuan, Chihchau; Pathak, Sayan; Sunkin, Susan M; Dang, Chinh; Bohland, Jason W; Bokil, Hemant; Mitra, Partha P; Puelles, Luis; Hohmann, John; Anderson, David J; Lein, Ed S; Jones, Allan R; Hawrylycz, Michael

    2009-03-01

    Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of genes in the Allen Brain Atlas (ABA). The AGEA includes three discovery tools for examining neuroanatomical relationships and boundaries: (1) three-dimensional expression-based correlation maps, (2) a hierarchical transcriptome-based parcellation of the brain and (3) a facility to retrieve from the ABA specific genes showing enriched expression in local correlated domains. The utility of this atlas is illustrated by analysis of genetic organization in the thalamus, striatum and cerebral cortex. The AGEA is a publicly accessible online computational tool integrated with the ABA (http://mouse.brain-map.org/agea). PMID:19219037

  7. Expression of inducible nitric oxide synthase in the brain tissue of rats at preoxygenation, hypoxia/reoxygenation

    Institute of Scientific and Technical Information of China (English)

    Hongzhi Chen; Lu Li; Hong Zhao

    2006-01-01

    BACKGROUND: The disorder of the respiratory and circulation system during the anesthesia and operation often can lead to severe hypoxia. Preoxygenation is a conventional therapy for treatment of hypoxia.OBJECTIVE: To observe the change in the expression of inducible nitric oxide synthase (iNOS), I.e. Brain tissue injury degree, in cerebral cortex of rats after hypoxia/reoxygenation under the condition of different levels of preoxygenation.DESIGN: Randomized controlled animal experiment.SETTING: Department of Anesthesiology and Central Laboratory, Shengjing Hospital Affiliated to China Medical University.MATERTALS: This experiment was carried out in the laboratory of Shengjing Hospital Affiliated to China Medical University from March 2003 to March 2004. Seventy-two male Wistar rats, weighing from 250 to 300 g,were provided by the Animal Experimental Room of Shengjing Hospital of China Medical University [License No. SYXK (Liao) 2003-0019]. Seventy-two rats were randomized into 3 groups: preoxygenation group, hypoxia group and reoxygentation group. Each group was divided into 4 subgroups, 6 rats in each subgroup.METHODS: 0.21, 0.50, 0.75 and 0.98 volume fraction of oxygen was given to 4 subgroups of preoxygenation group respectively. The rats in each subgroup of hypoxia group inhaled oxygen for 30 minutes according to the method of preoxygenation. Then, nitrogen gas replaced oxygen and was pumped into the cabin, and the volume fraction of oxygen was decreased to be 0.05 within 20 minutes. The rats in each subgroup of reoxygenation group were treated with the experimental methods of preoxygenation and hypoxia separately,then they were moved into the wide mouthed bottle with two-air-duct rubber stopper. Finally, oxygen was pumped and the volume fraction of oxygen reached over 0.98 within 20 minutes. After 24 hours, all the surviving rats were killed by decapitation. Cerebral tissue was sliced and stained by haematoxylin-eosin and then enveloped. Brain tissue injury

  8. Overview of upcoming INO facility

    International Nuclear Information System (INIS)

    The India based Neutrino Observatory (INO) will be an underground laboratory, at the Bodi Hills in the Theni district of Tamilnadu, housing experiments that will benefit from the low cosmic ray background there. The flagship experiment will make measurements on atmospheric muon neutrinos and antineutrinos using a 50 kiloton Iron Calorimetric (ICAL) detector. As ICAL will be magnetised, with an average B-field of about 1.3 Tesla, it will be able to clearly identify the charge of the muons produced in charged current interaction of muon neutrinos and hence the identity of the primary muon neutrino or antineutrino. One of the key goals of ICAL at INO is to identify the neutrino mass hierarchy, normal or inverted. It will also make precise measurements of some of the parameters in the neutrino mass matrix. Apart from ICAL, the underground laboratory will also house other experiments such as a search for neutrinoless double beta decay using a cryogenic tin bolometer and a cryogenic silicon bolometer for dark matter particles in the low mass (few GeV) range. The current status of the R and D effort including that of the prototype ICAL to be housed at the Inter Institutional Centre for High Energy Physics at Madurai will be presented. (author)

  9. Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS-stimulated macrophages from Schisandra chinensis

    International Nuclear Information System (INIS)

    A novel α-iso-cubebenol, which has anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, was isolated from the fruits of Schisandra chinensis. α-iso-cubebenol inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. Consistent with these findings, α-iso-cubebenol also reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at the protein and mRNA levels in a concentration-dependent manner. α-iso-cubebenol also inhibited LPS-induced nuclear translocation of the NF-κB p65 subunit. Furthermore, α-iso-cubebenol suppressed the phosphorylation of ERK, JNK, and p38 kinase induced by LPS. Since the novel α-iso-cubebenol blocked the production of several pro-inflammatory mediators induced by LPS in macrophages, the molecule can be useful material for the development of anti-inflammatory agents against bacterial infections or endotoxin.

  10. Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS-stimulated macrophages from Schisandra chinensis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, You Jin [Department of Horticultural Bioscience, Pusan National University, Miryang 627-706 (Korea, Republic of); Park, Sun Young [Korea BIO-IT Foundry Center, Pusan National University, Busan 609-735 (Korea, Republic of); Kim, Sun Gun; Park, Da Jung; Kang, Jum Soon [Department of Horticultural Bioscience, Pusan National University, Miryang 627-706 (Korea, Republic of); Lee, Sang Joon [Department of Microbiology, Pusan National University, Busan 609-735 (Korea, Republic of); Yoon, Sik [Department of Anatomy, School of Medicine, Pusan National University, Yangsan 626-770 (Korea, Republic of); Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-770 (Korea, Republic of); Kim, Young Hun [Korea BIO-IT Foundry Center, Pusan National University, Busan 609-735 (Korea, Republic of); Bae, Yoe-Sik, E-mail: yoesik@dau.ac.kr [Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Choi, Young-Whan, E-mail: ywchoi@pusan.ac.kr [Department of Horticultural Bioscience, Pusan National University, Miryang 627-706 (Korea, Republic of)

    2010-01-22

    A novel {alpha}-iso-cubebenol, which has anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, was isolated from the fruits of Schisandra chinensis. {alpha}-iso-cubebenol inhibited LPS-induced nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) production. Consistent with these findings, {alpha}-iso-cubebenol also reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at the protein and mRNA levels in a concentration-dependent manner. {alpha}-iso-cubebenol also inhibited LPS-induced nuclear translocation of the NF-{kappa}B p65 subunit. Furthermore, {alpha}-iso-cubebenol suppressed the phosphorylation of ERK, JNK, and p38 kinase induced by LPS. Since the novel {alpha}-iso-cubebenol blocked the production of several pro-inflammatory mediators induced by LPS in macrophages, the molecule can be useful material for the development of anti-inflammatory agents against bacterial infections or endotoxin.

  11. Purification of a peptide from seahorse, that inhibits TPA-induced MMP, iNOS and COX-2 expression through MAPK and NF-kappaB activation, and induces human osteoblastic and chondrocytic differentiation.

    Science.gov (United States)

    Ryu, BoMi; Qian, Zhong-Ji; Kim, Se-Kwon

    2010-03-30

    Ongoing efforts to search for naturally occurring, bioactive substances for the amelioration of arthritis have led to the discovery of natural products with substantial bioactive properties. The seahorse (Hippocampus kuda Bleeler), a telelost fish, is one source of known beneficial products, yet has not been utilized for arthritis research. In the present work, we have purified and characterized a bioactive peptide from seahorse hydrolysis. Among the hydrolysates tested, pronase E-derived hydrolysate exhibited the highest alkaline phosphatase (ALP) activity, a phenotype marker of osteoblast and chondrocyte differentiation. After its separation from the hydrolysate by several purification steps, the peptide responsible for the ALP activity was isolated and its sequence was identified as LEDPFDKDDWDNWK (1821Da). We have shown that the isolated peptide induces differentiation of osteoblastic MG-63 and chondrocytic SW-1353 cells by measuring ALP activity, mineralization and collagen synthesis. Our results indicate that the peptide acts during early to late stages of differentiation in MG-63 and SW-1353 cells. We also assessed the concentration dependence of the peptide's inhibition of MMP (-1, -3 and -13), iNOS and COX-2 expression after treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), a common form of phorbol ester. The peptide also inhibited NO production in MG-63 and SW-1353 cells. To elucidate the mechanisms by which the peptide acted, we examined its effects on TPA-induced MAPKs/NF-kappaB activation and determined that the peptide treatment significantly reduced p38 kinase/NF-kappaB in MG-63 cells and MAPKs/NF-kappaB in SW-1353 cells. PMID:20004183

  12. Impact of L-Carnitine and Cinnamon on Insulin-Like Growth Factor-1 and Inducible Nitric Oxide Synthase Gene Expression in Heart and Brain of Insulin Resistant Rats

    Directory of Open Access Journals (Sweden)

    Mona A. Mohamed

    2010-01-01

    Full Text Available Problem statement: Evaluate the effects of daily administration of L-carnitine and cinnamon extract for two weeks on the expression of Insulin-like Growth Factor-1 (IGF-1 and inducible Nitric Oxide Synthase (iNOS genes in cardiac and brain tissues of rats with Insulin Resistance (IR. Approach: Rats were divided into 4 groups (8 animals each: Group (1 rats fed control diet (60% starch as control while groups (2, 3 and 4 fed high fructose diet (60% fructose. At the beginning of the 3rd week of feeding, rats of group (3 were treated with L-carnitine (300 mg kg-1 body weight/day, i.p. and animals of group (4 received a daily oral dose of cinnamon aqueous extract (0.5 mL rat-1. The animals were maintained in their respective groups for 4 weeks. Results: Feeding high fructose diet causes significant reduction in Insulin Receptor Substrate-1 (IRS-1 (amounted 30.65% and elevation in iNOS expression (reached 51% in the cardiac tissues as compared to control. In brain tissues, the IGF-1 mRNA was reduced in fructose loaded groups (28.81%. Administration of either L-carnitine or cinnamon extract significantly improves the expression of the cardiac studied genes but with no effects on the brain tissues. Conclusion: The present study illustrated that CE was more potent than L-carnitine in improving the IR.

  13. Reelin expression during embryonic brain development in Crocodylus niloticus.

    Science.gov (United States)

    Tissir, F; Lambert De Rouvroit, C; Sire, J-Y; Meyer, G; Goffinet, A M

    2003-03-10

    The expression of reelin mRNA and protein was studied during embryonic brain development in the Nile crocodile Crocodylus niloticus, using in situ hybridization and immunohistochemistry. In the forebrain, reelin was highly expressed in the olfactory bulb, septal nuclei, and subpial neurons in the marginal zone of the cerebral cortex, dorsal ventricular ridge, and basal forebrain. At early stages, reelin mRNA was also detected in subventricular zones. In the diencephalon, the ventral lateral geniculate nuclei and reticular nuclei were strongly positive, with moderate expression in the habenula and focal expression in the hypothalamus. High expression levels were noted in the retina, the tectum, and the external granule cell layer of the cerebellum. In the brainstem, there was a high level of signal in cochleovestibular, sensory trigeminal, and some reticular nuclei. No expression was observed in the cortical plate or Purkinje cells. Comparison with reelin expression during brain development in mammals, birds, turtles, and lizards reveals evolutionarily conserved, homologous features that presumably define the expression profile in stem amniotes. The crocodilian cortex contains subpial reelin-positive cells that are also p73 positive, suggesting that they are homologous to mammalian Cajal-Retzius cells, although they express the reelin gene less intensely. Furthermore, the crocodilian cortex does not contain the subcortical reelin-positive cells that are typical of lizards but expresses reelin in subventricular zones at early stages. These observations confirm that reelin is prominently expressed in many structures of the embryonic brain in all amniotes and further emphasize the unique amplification of reelin expression in mammalian Cajal-Retzius cells and its putative role in the evolution of the cerebral cortex. PMID:12541309

  14. KLF6 and iNOS regulates apoptosis during respiratory syncytial virus infection

    OpenAIRE

    Mgbemena, Victoria; Segovia, Jesus; Chang, Te-Hung; Bose, Santanu

    2013-01-01

    Human respiratory syncytial virus (RSV) is a highly pathogenic lung-tropic virus that causes severe respiratory diseases. Enzymatic activity of inducible nitric oxide (iNOS) is required for NO generation. Although NO contributes to exaggerated lung disease during RSV infection, the role of NO in apoptosis during infection is not known. In addition, host trans-activator(s) required for iNOS gene expression during RSV infection is unknown. In the current study we have uncovered the mechanism of...

  15. Mirroring pain in the brain : emotional expression versus motor imitation

    NARCIS (Netherlands)

    Budell, Lesley; Kunz, Miriam; Jackson, Philip L; Rainville, Pierre

    2015-01-01

    Perception of pain in others via facial expressions has been shown to involve brain areas responsive to self-pain, biological motion, as well as both performed and observed motor actions. Here, we investigated the involvement of these different regions during emotional and motor mirroring of pain ex

  16. Expression and relevant research of MGMT and XRCC1 gene in differentgrades of brain glioma and normal brain tissues

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Zhang

    2015-01-01

    Objective: To explore and analyze expression and relevant research of MGMT and XRCC1 gene in different grades of brain glioma and normal brain tissues. Methods: 52 cases of patients with brain glioma treated in our hospital from December 2013 to December 2014, and 50 cases of normal brain-tissue patients with intracranial hypertension were selected, and proceeding test to the surgical resection of brain tissue of the above patients to determine its MGMT and XRCC1 protein content, sequentially to record the expression of MGMT and XRCC1 of both groups. Grading of tumors to brain glioma after operation was carried out, and the expression of MGMT and XRCC1 gene in brain tissues of different patients was analyzed and compared;finally the contingency tables of X2 test was used to analyze the correlation of XRCC1and MGMT. Results:Positive rate of MGMT expression in normal brain tissue was 2%,while positive rate of MGMT expression in brain glioma was 46.2%,which was obviously higher than that in normal brain tissues (χ2=26.85, P0.05), which had no statistical significance. There were 12 cases of patients whose MGMT protein expression was positive and XRCC1 protein expression was positive; there were 18 cases of patients whose MGMT protein expression was negative and XRCC1 protein expression was negative. Contingency tables of X2 test was used to analyze the correlation of XRCC1 and MGMT, which indicated that the expression of XRCCI and MGMT in brain glioma had no correlation (r=0.9%, P=0.353), relevancy of both was r=0.9%. Conclusions: Positive rate of the expression of MGMT and XRCC1 in brain glioma was obviously higher than that in normal brain tissues, but the distribution of different grades of brain glioma had no obvious difference, and MGMT and XRCC1 expression had no obvious correlation, which needed further research.

  17. Increased expression of osteopontin in brain arteriovenous malformations

    Institute of Scientific and Technical Information of China (English)

    XU Hong-zhi; QIN Zhi-yong; GU Yu-xiang; ZHOU Ping; XU Feng; CHEN Xian-cheng

    2012-01-01

    Background The precise mechanisms responsible for the development and growth of intracranial arteriovenous malformations (AVMs) remain unclear.Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions.This study aimed to analyze the expression of OPN in human brain AVMs.Methods The AVM nidus was surgically obtained from patients with AVM,whereas control brain artery specimens were surgically obtained from patients with epilepsy.Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of OPN mRNA in biopsy specimens.OPN protein expression was localized by immunohistochemistry.The statistical differences between different groups were assessed by two-way analysis of variance (ANOVA).Results We analyzed 36 brain AVM specimens and 8 control brain artery specimens.Eleven patients with brain AVM received embolization treatment,and five underwent gamma knife radiotherapy before resection.Nineteen patients with brain AVM had a history of hemorrhage from AVMs.The expression of OPN mRNA was significantly higher in AVMs than that in the control specimens (25.76±2.71 vs.21.46±2.01,P <0.01).There was no statistically significant difference in the extent of OPN mRNA expression between the AVM group with and that without history of hemorrhage (26.13±2.45 vs.25.34±2.99) or gamma knife radiotherapy (24.39±2.10 vs.24.53±1.85).However,the difference between the AVM group with and that without embolization treatment history was statistically significant (24.39±2.10 vs.28.80±1.13,P <0.01).In the group with gamma knife radiotherapy history,OPN expression was found in arteries with early-stage radio-effect.Conclusions OPN may contribute to the vascular instability of brain AVMs.It may play an important role in the pathophysiological process related to embolization treatment.

  18. Alpha-synuclein expression in the developing human brain.

    Science.gov (United States)

    Raghavan, Ravi; Kruijff, Loes de; Sterrenburg, Monique D; Rogers, Beverly B; Hladik, Christa L; White, Charles L

    2004-01-01

    Alpha (alpha)-synuclein is a presynaptic protein, abnormal expression of which has been associated with neurodegenerative and neoplastic diseases. It is abundant in the developing vertebrate central nervous system (CNS), but less is known about its developmental expression in the human CNS. Immunohistochemical expression of alpha-synuclein was studied in 39 fetal, perinatal, pediatric, and adolescent brains. Perikaryal expression of alpha-synuclein is observed as early as 11-wk gestation in the cortical plate. Several discrete neuronal groups in the hippocampus, basal ganglia, and brain stem express perikaryal alpha-synuclein by 20-wk gestation, persisting through the first few years of life. In the cerebellum, alpha-synuclein is present by 21-wk gestation and persists into adult life as a coarse granular neuropil reaction product in the internal granular layer, and as a diffuse neuropil "blush" in the molecular layer. The germinal matrix, glia, endothelial cells, external granular layer, Pukinje cells, and dentate neurons are consistently negative for alpha-synuclein. We conclude that alpha-synuclein is expressed very early in human gestation, and that its distribution and temporal sequence of expression varies in discrete neuronal groups. Perikaryal alpha-synuclein starts disappearing from the neuronal cytosol in early childhood, and only the neuropil retains immunoreactivity into adulthood. The reappearance of alpha-synuclein in the adult neuronal cytosol in certain disease processes may represent reemergence of cues from an earlier developmental stage as part of a stress response. PMID:15547775

  19. Investigation of G72 (DAOA expression in the human brain

    Directory of Open Access Journals (Sweden)

    Hirsch Steven

    2008-12-01

    Full Text Available Abstract Background Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO, supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. Methods The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. Results Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala, spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. Conclusion Our results suggest that native G72 protein is not normally present in the tissues that we analysed

  20. FTO is expressed in neurones throughout the brain and its expression is unaltered by fasting.

    Directory of Open Access Journals (Sweden)

    James S McTaggart

    Full Text Available Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed FTO gene are associated with obesity. Although the physiological functions of FTO remain unclear, food intake is often altered when Fto expression levels are manipulated. Furthermore, deletion of FTO from neurones alone has a similar effect on food intake to deletion of FTO in all tissues. These results indicate that FTO expression in the brain is particularly important. Considerable focus has been placed on the dynamic regulation of Fto mRNA expression in the hypothalamus after short-term (16-48 hour fasting, but results have been controversial. There are no studies that quantify FTO protein levels across the brain, and assess its alteration following short-term fasting. Using immunohistochemistry, we found that FTO protein is widely expressed in mouse brain, and present in the majority of neurones. Using quantitative Western blotting and RT-qPCR we show that FTO protein and mRNA levels in the hypothalamus, cerebellum and rostral brain are relatively uniform, and levels in the brain are higher than in skeletal muscles of the lower limbs. Fasting for 18 hours does not alter the expression pattern, or levels, of FTO protein and mRNA. We further show that the majority of POMC neurones, which are critically involved in food intake regulation, also express FTO, but that the percentage of FTO-positive POMC neurones is not altered by fasting. In summary, we find no evidence that Fto/FTO expression is regulated by short-term (18-hour fasting. Thus, it is unlikely that the hunger and increased post-fasting food intake caused by such food deprivation is driven by alterations in Fto/FTO expression. The widespread expression of FTO in neurones also suggests that physiological studies of this protein should not be limited to the hypothalamus.

  1. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  2. Aging and gene expression in the primate brain.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  3. FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting

    OpenAIRE

    James S McTaggart; Sheena Lee; Michaela Iberl; Chris Church; Cox, Roger D.; Ashcroft, Frances M.

    2011-01-01

    Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed FTO gene are associated with obesity. Although the physiological functions of FTO remain unclear, food intake is often altered when Fto expression levels are manipulated. Furthermore, deletion of FTO from neurones alone has a similar effect on food intake to deletion of FTO in all tissues. These results indicate that FTO expression in the brain is particularly important. Considerable focus has been placed on the...

  4. Body language in the brain: constructing meaning from expressive movement

    Directory of Open Access Journals (Sweden)

    Christine Marie Tipper

    2015-08-01

    Full Text Available This fMRI study investigated neural systems that interpret body language - the meaningful emotive expressions conveyed by body movement. Participants watched videos of performers engaged in modern dance or pantomime that conveyed specific themes such as hope, agony, lust, or exhaustion. We tested whether the meaning of an affectively laden performance was decoded in localized brain substrates as a distinct property of action separable from other superficial features, such as choreography, kinematics, performer, and low-level visual stimuli. A repetition suppression (RS procedure was used to identify brain regions that decoded the meaningful affective state of a performer, as evidenced by decreased activity when emotive themes were repeated in successive performances. Because the theme was the only feature repeated across video clips that were otherwise entirely different, the occurrence of RS identified brain substrates that differentially coded the specific meaning of expressive performances. RS was observed bilaterally, extending anteriorly along middle and superior temporal gyri into temporal pole, medially into insula, rostrally into inferior orbitofrontal cortex, and caudally into hippocampus and amygdala. Behavioral data on a separate task indicated that interpreting themes from modern dance was more difficult than interpreting pantomime; a result that was also reflected in the fMRI data. There was greater RS in left hemisphere, suggesting that the more abstract metaphors used to express themes in dance compared to pantomime posed a greater challenge to brain substrates directly involved in decoding those themes. We propose that the meaning-sensitive temporal-orbitofrontal regions observed here comprise a superordinate functional module of a known hierarchical action observation network, which is critical to the construction of meaning from expressive movement. The findings are discussed with respect to a predictive coding model of action

  5. Body language in the brain: constructing meaning from expressive movement.

    Science.gov (United States)

    Tipper, Christine M; Signorini, Giulia; Grafton, Scott T

    2015-01-01

    This fMRI study investigated neural systems that interpret body language-the meaningful emotive expressions conveyed by body movement. Participants watched videos of performers engaged in modern dance or pantomime that conveyed specific themes such as hope, agony, lust, or exhaustion. We tested whether the meaning of an affectively laden performance was decoded in localized brain substrates as a distinct property of action separable from other superficial features, such as choreography, kinematics, performer, and low-level visual stimuli. A repetition suppression (RS) procedure was used to identify brain regions that decoded the meaningful affective state of a performer, as evidenced by decreased activity when emotive themes were repeated in successive performances. Because the theme was the only feature repeated across video clips that were otherwise entirely different, the occurrence of RS identified brain substrates that differentially coded the specific meaning of expressive performances. RS was observed bilaterally, extending anteriorly along middle and superior temporal gyri into temporal pole, medially into insula, rostrally into inferior orbitofrontal cortex, and caudally into hippocampus and amygdala. Behavioral data on a separate task indicated that interpreting themes from modern dance was more difficult than interpreting pantomime; a result that was also reflected in the fMRI data. There was greater RS in left hemisphere, suggesting that the more abstract metaphors used to express themes in dance compared to pantomime posed a greater challenge to brain substrates directly involved in decoding those themes. We propose that the meaning-sensitive temporal-orbitofrontal regions observed here comprise a superordinate functional module of a known hierarchical action observation network (AON), which is critical to the construction of meaning from expressive movement. The findings are discussed with respect to a predictive coding model of action understanding

  6. Brain structural basis of cognitive reappraisal and expressive suppression

    OpenAIRE

    Hermann, Andrea; Bieber, Alexandra; Keck, Tanja; Vaitl, Dieter; Stark, Rudolf

    2013-01-01

    Cognitive reappraisal and expressive suppression, two major emotion regulation strategies, are differentially related to emotional well-being. The aim of this study was to test the association of individual differences in these two emotion regulation strategies with gray matter volume of brain regions that have been shown to be involved in the regulation of emotions. Based on high-resolution magnetic resonance images of 96 young adults voxel-based morphometry was used to analyze the gray matt...

  7. Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury.

    Science.gov (United States)

    Chen, X; Li, Y; Kline, A E; Dixon, C E; Zafonte, R D; Wagner, A K

    2005-01-01

    Alterations in brain-derived neurotrophic factor expression have been reported in multiple brain regions acutely after traumatic brain injury, however neither injury nor post-injury environmental enrichment has been shown to affect hippocampal brain-derived neurotrophic factor gene expression in male rats chronically post-injury. Studies have demonstrated hormone-related neuroprotection for female rats after traumatic brain injury, and estrogen and exercise both influence brain-derived neurotrophic factor levels. Despite recent studies suggesting that exposure post-traumatic brain injury to environmental enrichment improves cognitive recovery in male rats, we have shown that environmental enrichment mediated improvements with spatial learning are gender specific and only positively affect males. Therefore the purpose of this study was to evaluate the effect of gender and environmental enrichment on chronic post-injury cortical and hippocampal brain-derived neurotrophic factor protein expression. Sprague-Dawley male and cycling female rats were placed into environmental enrichment or standard housing after controlled cortical impact or sham surgery. Four weeks post-surgery, hippocampal and frontal cortex brain-derived neurotrophic factor expression were examined using Western blot. Results revealed significant increases in brain-derived neurotrophic factor expression in the frontal cortex ipsilateral to injury for males (P=0.03). Environmental enrichment did not augment this effect. Neither environmental enrichment nor injury significantly affected cortical brain-derived neurotrophic factor expression for females. In the hippocampus ipsilateral to injury brain-derived neurotrophic factor expression for both males and females was half (49% and 51% respectively) of that observed in shams housed in the standard environment. For injured males, there was a trend in this region for environmental enrichment to restore brain-derived neurotrophic factor levels to sham values

  8. Irradiation of rat brain reduces P-glycoprotein expression and function

    OpenAIRE

    Bart, J; Nagengast, W B; Coppes, R P; Wegman, T D; Graaf, W.T.A. van der; Groen, H J M; Vaalburg, W; de Vries, E G E; Hendrikse, N H

    2007-01-01

    The blood–brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces P-gp expression and function in the brain, right hemispheres of rats wer...

  9. Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

    Science.gov (United States)

    Zanello, S. B.; Stevens, B.; Calvillo, E.; Tang, R.; Gutierrez Flores, B.; Hu, L.; Skog, J.; Bershad, E.

    2016-01-01

    While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for

  10. Inhibitory effect of curcumin on NO production and iNOS expression of microglia BV-2 cells infected with Toxoplasma gondii%姜黄素对弓形虫感染小胶质细胞NO的产生及iNOS表达的影响

    Institute of Scientific and Technical Information of China (English)

    王璐; 张义华; 孔兰婷; 王为为; 张倩; 罗庆礼; 沈继龙; 沙泉

    2013-01-01

    The present study aims to investigate the inhibitory effect of curcumin on production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in microglia (BV-2 cells) infected with Toxoplasma gondii (PRU strain, genotype Ⅱ). BV-2 cells were inoculated with T. gondii (5 X 105 ) followed by exposure to curcumin. The morphology of BV-2 cells was observed under inverted microscope. The MTT assay was taken to check proliferation of BV-2 cells. The production of NO and expression of iNOS were determined with the Griess test and Western blotting, respectively. Results showed that compared with the control, BV-2 cells infected with T. gondii were presented in round and pseudopodia were remarkably reduced which indicated the retarded cell movements. The production of NO and expression of iNOS were significantly increased in BV-2 cells infected with T. gondii. The curcumin could down-regulate the production of NO and expression of iNOS. It's revealed that curcumin inhibits the expression of iNOS and the production of NO in microglia BV-2 cells infected with T. gondii (PRU, genotype Ⅱ) , suggesting a therapeutic potential in help with the treatment of toxoplasmosis.%目的 研究姜黄素(curcumin)对弓形虫PRU虫株(type II基因型)感染的BV-2细胞一氧化氮(NO)的产生及诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达的影响.方法 用弓形虫PRU虫株(5×105)感染BV-2细胞,同时用姜黄素进行干预,观察细胞形态;MTT检测细胞增殖;用Griess法检测细胞上清中NO的含量;Western blotting检测iNOS蛋白的表达.结果 与对照组相比,感染弓形虫的小胶质细胞胞体变圆,突起减少,姜黄素可以减轻这种改变.弓形虫感染的小胶质细胞iNOS的表达增强,NO释放量增加,且随着时间延长逐渐增高,姜黄素能抑制iNOS的表达和NO的产生.结论 姜黄素可以抑制弓形虫感染的BV-2细胞iNOS蛋白表达和NO的产生,提示该药对弓形虫脑病具有潜在的治疗价值.

  11. Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

    Institute of Scientific and Technical Information of China (English)

    Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin

    2011-01-01

    The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

  12. Arvamus / Edgar Krull, Väino Rajangu

    Index Scriptorium Estoniae

    Krull, Edgar

    2004-01-01

    Mida peaksid teadlased enne koolivõrgu põhjalikku korrastamist Eesti hariduselus veel uurima? Arvamust avaldavad Tartu Ülikooli haridusteaduskonna pedagoogika osakonna juhataja, prof Edgar Krull ja Tallinna Tehnikaülikooli haridusuuringute keskuse juhataja, prof Väino Rajangu

  13. India-based Neutrino Observatory (INO)

    Indian Academy of Sciences (India)

    D Indumathi

    2004-12-01

    We present some physics possibilities with an iron calorimeter detector (ICAL) and a status report on the feasibility study to construct such a detector at a future possible India-based Neutrino Observatory (INO). This talk was given at the workshop on high energy physics phenomenology, WHEPP-8, in Jan. 2004, at IIT Bombay.

  14. Selenoprotein S expression in reactive astrocytes following brain injury.

    Science.gov (United States)

    Fradejas, Noelia; Serrano-Pérez, Maria Del Carmen; Tranque, Pedro; Calvo, Soledad

    2011-06-01

    Selenoprotein S (SelS) is an endoplasmic reticulum (ER)-resident protein involved in the unfolded protein response. Besides reducing ER-stress, SelS attenuates inflammation by decreasing pro-inflammatory cytokines. We have recently shown that SelS is responsive to ischemia in cultured astrocytes. To check the possible association of SelS with astrocyte activation, here we investigate the expression of SelS in two models of brain injury: kainic acid (KA) induced excitotoxicity and cortical mechanical lesion. The regulation of SelS and its functional consequences for neuroinflammation, ER-stress, and cell survival were further analyzed using cultured astrocytes from mouse and human. According to our immunofluorescence analysis, SelS expression is prominent in neurons and hardly detectable in astrocytes from control mice. However, brain injury intensely upregulates SelS, specifically in reactive astrocytes. SelS induction by KA was evident at 12 h and faded out after reaching maximum levels at 3-4 days. Analysis of mRNA and protein expression in cultured astrocytes showed SelS upregulation by inflammatory stimuli as well as ER-stress inducers. In turn, siRNA-mediated SelS silencing combined with adenoviral overexpression assays demonstrated that SelS reduces ER-stress markers CHOP and spliced XBP-1, as well as inflammatory cytokines IL-1β and IL-6 in stimulated astrocytes. SelS overexpression increased astrocyte resistance to ER-stress and inflammatory stimuli. Conversely, SelS suppression compromised astrocyte viability. In summary, our results reveal the upregulation of SelS expression in reactive astrocytes, as well as a new protective role for SelS against inflammation and ER-stress that can be relevant to astrocyte function in the context of inflammatory neuropathologies. PMID:21456042

  15. NMO in pediatric patients: brain involvement and clinical expression

    Directory of Open Access Journals (Sweden)

    Joaquín A. Peña

    2011-02-01

    Full Text Available OBJECTIVE: To analyze the clinical, neuroimaging characteristics and positivity of the acquaporin water channel (NMO-IgG in pediatric patients with neuromyelitis optica (NMO. This disorder could have a variable clinical expression. To address such variability, the term NMO spectrum has been suggested. METHOD: We evaluated six pediatric patients, with a median age of 11 years at the time of the study, with the diagnosis of NMO by the Wingerchuck criteria. RESULTS: All the cases exhibited bilateral optic neuritis (ON. Four patients had abnormalities on brain MRI from the onset,although only three of them developed symptoms correlated to those lesions during the course of their disorder. NMO-IgG was positive in 80%. CONCLUSION: Optic neuropathy is the most impaired feature in NMO patients. Brain MRI lesions are not compatible with multiple sclerosis and positivity of the NMO-IgG are also present in NMO pediatric patients, confirming the heterogeneity in the expression of this disorder.

  16. Behavioral stress reduces RIP140 expression in astrocyte and increases brain lipid accumulation

    OpenAIRE

    Feng, Xudong; Lin, Yu-Lung; Wei, Li-Na

    2015-01-01

    Receptor-interacting protein 140 (RIP140) is highly expressed in the brain, and acts in neurons and microglia to affect emotional responses. The present study reveals an additional function of RIP140 in the brain, which is to regulate brain lipid homeostasis via its action in astrocytes. We found forced swim stress (FSS) significantly reduces the expression level of RIP140 and elevates cholesterol content in the brain. Mechanistically, FSS elevates endoplasmic reticulum stress, which suppress...

  17. Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury

    OpenAIRE

    Cooney, Sean J.; Bermudez-Sabogal, Sara L; Byrnes, Kimberly R.

    2013-01-01

    Background Brain injury results in an increase in the activity of the reactive oxygen species generating NADPH oxidase (NOX) enzymes. Preliminary studies have shown that NOX2, NOX3, and NOX4 are the most prominently expressed NOX isotypes in the brain. However, the cellular and temporal expression profile of these isotypes in the injured and non-injured brain is currently unclear. Methods Double immunofluorescence for NOX isotypes and brain cell types was performed at acute (24 hours), sub-ac...

  18. Correlation of inducible nitric oxide synthase (iNOS) inhibition with TNF-α, caspase-1, FasL and TLR-3 in pathogenesis of rabies in mouse model.

    Science.gov (United States)

    Madhu, B P; Singh, K P; Saminathan, M; Singh, R; Tiwari, A K; Manjunatha, V; Harish, C; Manjunathareddy, G B

    2016-02-01

    The role of inflammatory cytokines such as interleukin-1α/β (IL-1α/β), IL-6, IL-10, tumour necrosis factor-alpha (TNF-α), interferons, nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in pathogenesis of rabies is being actively pursued. Presently, levels of certain immune molecules in pathogenesis of rabies in mice have been investigated. CVS strain of rabies infection resulted in early increase in iNOS, TNF-α, caspase-1, Fas ligand (FasL) and toll-like receptor-3 (TLR-3) mRNA levels in brain, and nitric oxide levels in serum. The severity of clinical signs and microscopic lesions largely correlated with NO levels. Aminoguanidine (AG; iNOS inhibitor) decreased NO production with delay in development of clinical signs and increase in survival time. Prolonged survival time correlated with reduced viral load evident by real-time PCR, reduced fluorescent signals of rabies antigen in brain and reduced immunohistochemistry signals in neuronal cytoplasm. These parameters suggested that nitric oxide did influence the rabies virus replication. Inhibition of iNOS by AG administration led to decreased expression of TNF-α, caspase-1, FasL and TLR-3 mRNA levels suggesting that increase in NO levels in rabies virus infection possibly contributed to development of disease through inflammation, apoptosis and immune-evasive mechanisms. PMID:26690069

  19. Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS

    OpenAIRE

    Aldo Gerbino; Salvatore Provenzano; Maria Buscemi; Annamaria Mauro

    2011-01-01

    Full-term human umbilical cord contains three blood vessels: two arteries coiled around a vein and surrounded by Wharton’s jelly, a mucous tissue with few mesenchymal stromal cells and abundant extracellular matrix. Umbilical vessels lack innervations, thus endothelial cells must play a role in the control of blood flow. The aim of this study was to investigate in human umbilical cord the expression of five peptides that could be involved in the regulation of vascular tone: Orphanin...

  20. Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain

    OpenAIRE

    Pathak Sayan; Thompson Carol; Ng Lydia; Lau Christopher; Kuan Leonard; Jones Allan; Hawrylycz Mike

    2008-01-01

    Abstract Background Spatially mapped large scale gene expression databases enable quantitative comparison of data measurements across genes, anatomy, and phenotype. In most ongoing efforts to study gene expression in the mammalian brain, significant resources are applied to the mapping and visualization of data. This paper describes the implementation and utility of Brain Explorer, a 3D visualization tool for studying in situ hybridization-based (ISH) expression patterns in the Allen Brain At...

  1. 问号钩端螺旋体对J774A.1和THP-1细胞iNOS表达及NO水平的影响%Expression of iNOS and levels of NO in THP-1 and J774A. 1 cells during Leptospira interrogans infec-tion

    Institute of Scientific and Technical Information of China (English)

    李沛丽; 刘英; 马青; 韦小瑜; 游旅; 唐光鹏; 王定明; 周碧君; 李世军

    2015-01-01

    目的:了解问号钩端螺旋体(简称钩体)对小鼠和人单核-巨噬细胞株诱导型一氧化氮合酶(iNOS)表达及一氧化氮(NO)水平的影响,了解不同宿主巨噬细胞对问号钩体的杀菌机制。方法采用问号钩体56601株感染J774A.1及人单核细胞株THP-1建立钩体细胞感染模型,采用re-al-time RT-PCR法和流式细胞术分别测定细胞iNOS mRNA和蛋白表达水平。采用 Griess法测定细胞NO水平。结果 Real-time RT-PCR测定结果显示,问号钩体感染2、4、12和24 h的J774A.1细胞iNOS mRNA表达水平较未感染细胞分别上调1.37、2.82、25.76和27.47倍,THP-1细胞iNOS mRNA表达水平较未感染细胞上调1.59、3.98、3.89和8.81倍。流式细胞术测定结果显示,问号钩体感染2、4、12和24 h的J774A.1细胞iNOS蛋白表达率分别从感染前的34.16%上升至85.85%、93.82%、91.77%和93.65%,THP-1细胞iNOS 蛋白表达率分别从感染前的22.08%上升至72.64%、81.33%、80.03%和65.72%。 Griess法测定结果显示,问号钩体感染2、4、12和24 h的J774A.1细胞NO水平从感染前的0.1588μmol/L上升至0.2208、0.2668、0.3808和0.3828μmol/L,THP-1细胞NO水平分别从感染前的0.0988μmol/L上升至0.2848、0.3228、0.2608和0.3308μmol/L。结论问号钩体感染的J774A.1和THP-1细胞 iNOS mRNA与蛋白表达水平及NO产生量均显著上调,尤以J774A.1细胞上调更为明显,结果有助于揭示不同宿主巨噬细胞对问号钩体的杀菌机制。%Objective To investigate the expression of inducible nitric oxide synthase ( iNOS) and the levels of nitric oxide (NO) in THP-1 and J774A. 1 cells during Leptospira interrogans (L. interrogans) infection for a better understanding of the mechanism of macrophages involved defense against L. interrogans strains in different hosts. Methods The human mononuclear macrophages (THP-1) and the murine mono-nuclear macrophages (J774A. 1) were infected with L. interrogans strain 56601. The expression of iNOS

  2. 乌司他丁对脂多糖诱导的巨噬细胞NO释放和iNOSmRNA表达的影响%Effect of Ulinastatin on the Lipopolysaccharide-induced Production of Nitric Oxide and mRNA Expression of iNOS in Macrophages

    Institute of Scientific and Technical Information of China (English)

    黄春燕; 赵艳琼; 李慕军; 邝晓聪; 黄玲玲; 钟琳琳; 唐

    2012-01-01

    Objective To investigate the effect of ulinastatin on the lipopolysacchaiide( LPS )-induced production of nitric oxide( NO ) and the mRNA expression of inducible nitric oxide synthase( iNOS ) in macrophages. Methods The RAW264.7 macrophage cells activated with LPS were pretreated with ulinastatin of different concentrations ( 100 - 10 000 U/ml ). The production of NO was determined by the Criess test. The mRNA expression of iNOS was determined by Real-time RT-PCR. Results Ulinastatin,especially in high concentration ranges( 1 000 -10 000 U/ml), inhibited LPS-induced production of NO( P 0.05 ). Conclusion High concentration ulinastatin can inhibit the production of NO and mRNA expression of iNOS in LPS-induced macrophages, and the effect is correlated with the concentration of ulinastatin.%目的 探讨乌司他丁对脂多糖(LPS)诱导的RAW264.7细胞一氧化氮(NO)释放和诱生型一氧化氮合酶(iNOSmRNA)表达的影响.方法 应用LPS激活RAW264.7细胞株,与不同浓度组乌司他丁(100~10 000 U/ml)共同孵育,Griess试剂法测定NO释放量;实时荧光定量反转录聚合酶链反应(RT-PCR)技术分析iNOSmRNA的表达.结果 高浓度的乌司他丁(1 000~ 10 000 U/ml)能抑制LPS诱导的RAW264.7细胞NO的表达(P<0.05),下调iNOSmRNA含量(P<0.05);低浓度乌司他丁(100 U/ml)对LPS诱导的RAW264.7细胞NO、iNOSmRNA表达与LPS单独处理组比较,差异无统计学意义(P>0.05).结论 高浓度乌司他丁抑制LPS诱导的巨噬细胞NO释放和iNOSmRNA表达,这种抑制与浓度相关.

  3. Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain

    Directory of Open Access Journals (Sweden)

    Pathak Sayan

    2008-03-01

    Full Text Available Abstract Background Spatially mapped large scale gene expression databases enable quantitative comparison of data measurements across genes, anatomy, and phenotype. In most ongoing efforts to study gene expression in the mammalian brain, significant resources are applied to the mapping and visualization of data. This paper describes the implementation and utility of Brain Explorer, a 3D visualization tool for studying in situ hybridization-based (ISH expression patterns in the Allen Brain Atlas, a genome-wide survey of 21,000 expression patterns in the C57BL6J adult mouse brain. Results Brain Explorer enables users to visualize gene expression data from the C57Bl/6J mouse brain in 3D at a resolution of 100 μm3, allowing co-display of several experiments as well as 179 reference neuro-anatomical structures. Brain Explorer also allows viewing of the original ISH images referenced from any point in a 3D data set. Anatomic and spatial homology searches can be performed from the application to find data sets with expression in specific structures and with similar expression patterns. This latter feature allows for anatomy independent queries and genome wide expression correlation studies. Conclusion These tools offer convenient access to detailed expression information in the adult mouse brain and the ability to perform data mining and visualization of gene expression and neuroanatomy in an integrated manner.

  4. Cosmic ray test of INO RPC stack

    International Nuclear Information System (INIS)

    The India-based Neutrino Observatory (INO) collaboration is planning to build a 50 kt magnetised iron calorimeter (ICAL) detector using glass Resistive Plate Chambers (RPCs) as active detector elements. A stack of 12 such glass RPCs of 1 m ×1 m in area is tracking cosmic ray muons for over three years. In this paper, we will review the constructional aspects of the stack and discuss the performance of the RPCs using this cosmic ray data.

  5. Review of terahertz technology development at INO

    Science.gov (United States)

    Dufour, Denis; Marchese, Linda; Terroux, Marc; Oulachgar, Hassane; Généreux, Francis; Doucet, Michel; Mercier, Luc; Tremblay, Bruno; Alain, Christine; Beaupré, Patrick; Blanchard, Nathalie; Bolduc, Martin; Chevalier, Claude; D'Amato, Dominic; Desroches, Yan; Duchesne, François; Gagnon, Lucie; Ilias, Samir; Jerominek, Hubert; Lagacé, François; Lambert, Julie; Lamontagne, Frédéric; Le Noc, Loïc; Martel, Anne; Pancrati, Ovidiu; Paultre, Jacques-Edmond; Pope, Tim; Provençal, Francis; Topart, Patrice; Vachon, Carl; Verreault, Sonia; Bergeron, Alain

    2015-10-01

    Over the past decade, INO has leveraged its expertise in the development of uncooled microbolometer detectors for infrared imaging to produce terahertz (THz) imaging systems. By modifying its microbolometer-based focal plane arrays to enhance absorption in the THz bands and by developing custom THz imaging lenses, INO has developed a leading-edge THz imaging system, the IRXCAM-THz-384 camera, capable of exploring novel applications in the emerging field of terahertz imaging and sensing. Using appropriate THz sources, results show that the IRXCAM-THz-384 camera is able to image a variety of concealed objects of interest for applications such as non-destructive testing and weapons detections. By using a longer wavelength (94 GHz) source, it is also capable of sensing the signatures of various objects hidden behind a drywall panel. This article, written as a review of THz research at INO over the past decade, describes the technical components that form the IRXCAM-THz-384 camera and the experimental setup used for active THz imaging. Image results for concealed weapons detection experiments, an exploration of wavelength choice on image quality, and the detection of hidden objects behind drywall are also presented.

  6. Sodium nitroprusside has leishmanicidal activity independent of iNOS

    Directory of Open Access Journals (Sweden)

    Natália Yoshie Kawakami

    2016-02-01

    Full Text Available Abstract: INTRODUCTION: Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania . Cutaneous leishmaniasis is the most common form, with millions of new cases worldwide each year. Treatments are ineffective due to the toxicity of existing drugs and the resistance acquired by certain strains of the parasite. METHODS: We evaluated the activity of sodium nitroprusside in macrophages infected with Leishmania (Leishmania amazonensis . Phagocytic and microbicidal activity were evaluated by phagocytosis assay and promastigote recovery, respectively, while cytokine production and nitrite levels were determined by ELISA and by the Griess method. Levels of iNOS and 3-nitrotyrosine were measured by immunocytochemistry. RESULTS: Sodium nitroprusside exhibited in vitro antileishmanial activity at both concentrations tested, reducing the number of amastigotes and recovered promastigotes in macrophages infected with L. amazonensis . At 1.5µg/mL, sodium nitroprusside stimulated levels of TNF-α and nitric oxide, but not IFN-γ. The compound also increased levels of 3-nitrotyrosine, but not expression of iNOS, suggesting that the drug acts as an exogenous source of nitric oxide. CONCLUSIONS: Sodium nitroprusside enhances microbicidal activity in Leishmania -infected macrophages by boosting nitric oxide and 3-nitrotyrosine.

  7. Correlation between heat shock protein 70 expression in the brain stem and sudden death after experimental traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    ZHAO Lian-xu; XU Xiao-hu; LIU Chao; PAN Su-yue; ZHU Jia-zhen; ZHANG Cheng

    2001-01-01

    Objective: The aim of this study was to determine the patterns of heat-shock protein 70 (HSP70) biosynthesis following traumatic brain injury, and observe the effect of HSP70 induction on the function of the vital center in the brain stem. Methods: Rat models of sudden death resulted form traumatic brain injury were produced, and HSP70 expression in the rat brain stem was determined by immunohistochemistry, the induction of HSP70 mRNA detected by RT-PCR. Results: The level of HSP70 mRNA was prominently elevated in the brain stem as early as 1 5 min following the impact injury, while HSP70 expression was only observed 3 to 6 h after the injury. It was also observed that the levels of HSP70 mRNA but not the protein were elevated in the brain stem of sudden death rats. Conclusion: The synthesis of HSP70 was significantly enhanced in the brain stem following traumatic injury, and the expression of HSP70 is beneficial to eliminate the stress agents, and to sustain the cellular protein homeostasis. When the injury disturbs the synthesis of HSP70 to disarm the protective mechanism of heat-shock proteins, dysfunction of the vital center in the brain stem, and consequently death may occur. Breach in the synchronization of HSP70 mRNA-protein can be indicative of fatal damage to the nerve cells.

  8. Expression of PHB2 in Rat Brain Cortex Following Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Ting Xu

    2014-02-01

    Full Text Available Prohibitin2 (PHB2 is a ubiquitous, evolutionarily strongly conserved protein. It is one of the components of the prohibitin complex, which comprises two highly homologous subunits, PHB1 and PHB2. PHB2 is present in various cellular compartments including the nucleus and mitochondria. Recent studies have identified PHB2 as a multifunctional protein that controls cell proliferation, apoptosis, cristae morphogenesis and the functional integrity of mitochondria. However its distribution and function in the central nervous system (CNS are not well understood. In this study, we examined PHB2 expression and cellular localization in rats after acute traumatic brain injury (TBI. Western Blot analysis showed PHB2 level was significantly enhanced at five days after injury compared to control, and then declined during the following days. The protein expression of PHB2 was further analyzed by immunohistochemistry. In comparison to contralateral cerebral cortex, we observed a highly significant accumulation of PHB2 at the ipsilateral brain. Immunofluorescence double-labeling showed that PHB2 was co-expressed with NeuN, GFAP. Besides, PHB2 also colocalized with activated caspase-3 and PCNA. To further investigate the function of PHB2, primary cultured astrocytes and the neuronal cell line PC12 were employed to establish a proliferation model and an apoptosis model, respectively, to simulate the cell activity after TBI to a certain degree. Knocking down PHB2 by siRNA partly increased the apoptosis level of PC12 stimulated by H2O2. While the PHB2 was interrupted by siRNA, the proliferation level of primary cultured astrocytes was inhibited notably than that in the control group. Together with our data, we hypothesized that PHB2 might play an important role in CNS pathophysiology after TBI.

  9. Aquaporin 4 expression and ultrastructure of the blood-brain barrier following cerebral contusion injury

    Institute of Scientific and Technical Information of China (English)

    Xinjun Li; Yangyun Han; Hong Xu; Zhongshu Sun; Zengjun Zhou; Xiaodong Long; Yumin Yang; Linbo Zou

    2013-01-01

    This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2–72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelial cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.

  10. 通络方药对2型糖尿病大鼠心肌和主动脉iNOS基因表达的影响%Effect of tongluo recipe on the expression of iNOS mRNA in myocardium and aorta of type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    李文桐; 孙亮亮; 邹俊杰; 刘志民

    2013-01-01

    目的 观察通络方药(Tongluo Recipe,TLR)对2型糖尿病大鼠心肌和主动脉诱导型一氧化氮合酶(iNOS)基因表达的影响,探讨TLR在2型糖尿病(type 2 diabetes,T2DM)的干预作用和应用价值.方法 30只雄性健康清洁级SD大鼠随机分为3组:正常对照组、T2DM组、T2DM+ TLR干预组,每组10只.T2DM+ TLR干预组大鼠TLR按0.4g·kg-1·d(1)剂量灌胃,1次/d,持续给药12w后处死取心肌、主动脉组织待测.利用实时定量逆转录多聚酶链反应(RT-PCR)方法测定各组大鼠心肌、主动脉诱导型一氧化氮合酶iNOS的基因表达水平.结果 与正常对照组比较,2型DM组大鼠心肌和主动脉iNOS的mRNA表达明显降低(P<0.01、P<0.05),而T2DM+ TLR干预组大鼠心肌和主动脉iNOS的mRNA表达较T2DM组明显升高(P<0.01).结论 TLR可以增加T2DM大鼠心肌、主动脉iNOS的mRNA表达,从而增加NO合成,可能对T2DM具有防治意义.%Objective To investigate the intervention and application value of Tongluo Recipe (TLR) in type 2 diabetes by detecting the expression of iNOS rnRNA in myocardium and aorta of type 2 diabetic rats.Methods Thirty SD healthy rats were randomly divided into 3 groups:normal control group,type 2 diabetes group,and type 2 diabetes + TLR intervention group.There were 10 rats in every group.The rats in type 2 diabetes + TLR intervention group were treated with TLR of 0.4 g· kg-1 · d1 dose via gavage.All rats were sacrificed after 12 weeks intervention and the myocardium and aorta of rats were obtained.Results Comparing with the normal control group,the levels of the expression of iNOS mRNA in myocardium and aorta in the type 2 diabetes group were significantly decreased (P<0.01,P<0.05).But the levels of the expression of iNOS mRNA in the type 2 diabetes + TLR intervention group were significantly increased as compared to the type 2 diabetes group (P<0.01).Conclusion TLR may treat and prevent T2DM via increasing the expression of iNOS mRNA in

  11. Rate of evolution in brain-expressed genes in humans and other primates.

    Directory of Open Access Journals (Sweden)

    Hurng-Yi Wang

    2007-02-01

    Full Text Available Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM and then conducted three-way comparisons among (i mouse, OWM, and human, and (ii OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse, a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i faster evolution in gene expression, and (ii a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.

  12. MEMS/MOEMS foundry services at INO

    Science.gov (United States)

    García-Blanco, Sonia; Ilias, Samir; Williamson, Fraser; Généreux, Francis; Le Noc, Loïc; Poirier, Michel; Proulx, Christian; Tremblay, Bruno; Provençal, Francis; Desroches, Yan; Caron, Jean-Sol; Larouche, Carl; Beaupré, Patrick; Fortin, Benoit; Topart, Patrice; Picard, Francis; Alain, Christine; Pope, Timothy; Jerominek, Hubert

    2010-06-01

    In the MEMS manufacturing world, the "fabless" model is getting increasing importance in recent years as a way for MEMS manufactures and startups to minimize equipment costs and initial capital investment. In order for this model to be successful, the fabless company needs to work closely with a MEMS foundry service provider. Due to the lack of standardization in MEMS processes, as opposed to CMOS microfabrication, the experience in MEMS development processes and the flexibility of the MEMS foundry are of vital importance. A multidisciplinary team together with a complete microfabrication toolset allows INO to offer unique MEMS foundry services to fabless companies looking for low to mid-volume production. Companies that benefit from their own microfabrication facilities can also be interested in INO's assistance in conducting their research and development work during periods where production runs keep their whole staff busy. Services include design, prototyping, fabrication, packaging, and testing of various MEMS and MOEMS devices on wafers fully compatible with CMOS integration. Wafer diameters ranging typically from 1 inch to 6 inches can be accepted while 8-inch wafers can be processed in some instances. Standard microfabrication techniques such as metal, dielectric, and semiconductor film deposition and etching as well as photolithographic pattern transfer are available. A stepper permits reduction of the critical dimension to around 0.4 μm. Metals deposited by vacuum deposition methods include Au, Ag, Al, Al alloys, Ti, Cr, Cu, Mo, MoCr, Ni, Pt, and V with thickness varying from 5 nm to 2 μm. Electroplating of several materials including Ni, Au and In is also available. In addition, INO has developed and built a gold black deposition facility to answer customer's needs for broadband microbolometric detectors. The gold black deposited presents specular reflectance of less than 10% in the wavelength range from 0.2 μm to 100 μm with thickness ranging from

  13. Brain Activity while Reading Sentences with Kanji Characters Expressing Emotions

    Science.gov (United States)

    Yuasa, Masahide; Saito, Keiichi; Mukawa, Naoki

    In this paper, we describe the brain activity associated with kanji characters expressing emotion, which are places at the end of a sentence. Japanese people use a special kanji character in brackets at the end of sentences in text messages such as those sent through e-mail and messenger tools. Such kanji characters plays a role to expresses the sender's emotion (such as fun, laughter, sadness, tears), like emoticons. It is a very simple and effective way to convey the senders' emotions and his/her thoughts to the receiver. In this research, we investigate the effects of emotional kanji characters by using an fMRI study. The experimental results show that both the right and left inferior frontal gyrus, which have been implicated on verbal and nonverbal information, were activated. We found that we detect a sentence with an emotional kanji character as the verbal and nonverval information, and a sentence with emotional kanji characters enrich communication between the sender and the reciever.

  14. Characterization of iNOS+ Neutrophil-like ring cell in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Virtuoso Lauren P

    2012-07-01

    Full Text Available Abstract Background Myeloid-derived Suppressor Cells (MDSC have been identified as tumor-induced immature myeloid cells (IMC with potent immune suppressive activity in cancer. Whereas strict phenotypic classification of MDSC has been challenging due to the highly heterogeneous nature of cell surface marker expression, use of functional markers such as Arginase and inducible nitric oxide synthase (iNOS may represent a better categorization strategy. In this study we investigated whether iNOS could be utilized as a specific marker for the identification of a more informative homogenous MDSC subset. Methods Single-cell suspensions from tumors and other organs were prepared essentially by enzymatic digestion. Flow cytometric analysis was performed on a four-color flow cytometer. Morphology, intracellular structure and localization of iNOS+ ring cells in the tumor were determined by cytospin analysis, immunofluorescence microscopy and immunohistochemistry, respectively. For functional analysis, iNOS+ ring subset were sorted and tested in vitro cell culture experiments. Pharmacologic inhibition of iNOS was performed both in vivo and in vitro. Results The results showed that intracellular iNOS staining distinguished a granular iNOS+ SSChi CD11b+ Gr-1dim F4/80+ subset with ring-shaped nuclei (ring cells among the CD11b+ Gr-1+ cell populations found in tumors. The intensity of the ring cell infiltrate correlated with tumor size and these cells constituted the second major tumor-infiltrating leukocyte subset found in established tumors. Although phenotypic analysis demonstrated that ring cells shared characteristics with tumor-associated macrophages (TAM, morphological analysis revealed a neutrophil-like appearance as detected by cytospin and immunofluorescence microscopy analysis. The presence of distinct iNOS filled granule-like structures located next to the cell membrane suggested that iNOS was stored in pre-formed vesicles and available for rapid

  15. Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data

    OpenAIRE

    Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

    2015-01-01

    Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significa...

  16. EXPRESSION OF IL-13Ra2 GENE IN HUMAN BRAIN TUMORS

    Institute of Scientific and Technical Information of China (English)

    WU An-hua; TIE Xin-xin; WANG Yun-jie; YANG Guo-rui

    2005-01-01

    Objective: To investigate the expression of IL-13Ra2 gene in brain tumors. Methods: Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expression was evaluated by reverse transcriptase polymerase chain reaction and immunohistochemical analysis. Results: IL-13Ra2 gene was highly expressed in glioblastoma, medulloblastoma, malignant meningioma and benign meningioma. Conclusion:Human IL-13Ra2 gene is expressed in brain tumors in addition to gliomas, and our result indicates that the IL-13Ra2 gene promoter based gene therapy method can be used to treat brain tumors in addition to gliomas. Further studies involving larger numbers of samples are necessary to fully understand the expression profile of IL-13Ra2 gene in the brain tumors.

  17. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  18. Expression change in Angiopoietin-1 underlies change in relative brain size in fish.

    Science.gov (United States)

    Chen, Yu-Chia; Harrison, Peter W; Kotrschal, Alexander; Kolm, Niclas; Mank, Judith E; Panula, Pertti

    2015-07-01

    Brain size varies substantially across the animal kingdom and is often associated with cognitive ability; however, the genetic architecture underpinning natural variation in these key traits is virtually unknown. In order to identify the genetic architecture and loci underlying variation in brain size, we analysed both coding sequence and expression for all the loci expressed in the telencephalon in replicate populations of guppies (Poecilia reticulata) artificially selected for large and small relative brain size. A single gene, Angiopoietin-1 (Ang-1), a regulator of angiogenesis and suspected driver of neural development, was differentially expressed between large- and small-brain populations. Zebra fish (Danio rerio) morphants showed that mild knock down of Ang-1 produces a small-brained phenotype that could be rescued with Ang-1 mRNA. Translation inhibition of Ang-1 resulted in smaller brains in larvae and increased expression of Notch-1, which regulates differentiation of neural stem cells. In situ analysis of newborn large- and small-brained guppies revealed matching expression patterns of Ang-1 and Notch-1 to those observed in zebrafish larvae. Taken together, our results suggest that the genetic architecture affecting brain size in our population may be surprisingly simple, and Ang-1 may be a potentially important locus in the evolution of vertebrate brain size and cognitive ability. PMID:26108626

  19. Effect of calmodulin inhibitor on NO production and iNOS expression induced by LPS/IFN-γin RAW264.7 cells%CaM抑制剂对LPS/IFN-γ诱导的RAW264.7细胞NO生成及iNOS表达的影响

    Institute of Scientific and Technical Information of China (English)

    袁小媚; 雷寒; 柳青; 夏勇; 马康华

    2011-01-01

    Objective To investigate the effect of calmodulin (CaM) inhibitor on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) in mouse RAW264.7 macrophage cells, and to study the anti-inflammation mechanism of CaM inhibitor. Methods An inflammatory response model was established using RAW264.7 cells induced by LPS and/or IFN-γ. CaM inhibitors N-(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide (W-7) and triflu operazine (TFP) were used to pre-treat RAW264.7 cells to evaluate the effects of the CaM inhibitors. NO con centration was measured with Griess Reagent Kit. Target protein and mRNA expression was tested by Western blot and RT-PCR. Results In RAW264.7 cells induced by LPS or IFN-γ CaM inhibitors W-7 and TFP sig nificantly blocked NO production ( P < 0. 01 ) and protein and mRNA expression of iNOS ( P < 0. 01 ). In RAW264.7 cells induced by LPS and IFN-γ, W-7 and TFP remarkably prevented IKBα degradation (P < 0. 01 ) and phospho-IKK and phospho-STAT1 protein expression ( P < 0. 01 ). Conclusion CaM inhibitors W-7 and TFP can inhibit LPS/IFN-γ-induced NO production and iNOS protein and mRNA expression in RAW264.7 cells, probably by the mechanism of suppressing IKBα degradation and phospho-IKK and phospho- STAT1 protein expression. The anti-inflammatory effects of CaM inhibitors may be associated with NF-KB and JAK-STAT1 signaling pathways.%目的 观察钙调蛋白(Calmodulin,CaM)抑制剂对脂多糖/干扰素γ(LPS/IFN-γ)诱导的RAW264.7细胞一氧化氮(NO)的生成及诱生型一氧化氮合酶(iNOS)表达的作用及其可能的作用机制.方法 采用LPS/IFN-γ诱导RAW264.7巨噬细胞建立细胞炎症反应模型,钙调蛋白抑制剂(W-7,TFP)预处理细胞后,采用Griess试剂法测定NO释放量;采用Western blot法测定目的 蛋白的表达;采用反转录聚合酶链反应法(RT-PCR)分析iNOS mRNA表达的变化.结果 CaM抑制剂

  20. Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain

    Science.gov (United States)

    Jiao, S.; Schultz, E.; Wolff, J. A.

    1992-01-01

    After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain.

  1. Expression of the Otx2 homeobox gene in the developing mammalian brain: embryonic and adult expression in the pineal gland

    DEFF Research Database (Denmark)

    Rath, Martin F; Muñoz, Estela; Ganguly, Surajit;

    2006-01-01

    Otx2 is a vertebrate homeobox gene, which has been found to be essential for the development of rostral brain regions and appears to play a role in the development of retinal photoreceptor cells and pinealocytes. In this study, the temporal expression pattern of Otx2 was revealed in the rat brain......, with special emphasis on the pineal gland throughout late embryonic and postnatal stages. Widespread high expression of Otx2 in the embryonic brain becomes progressively restricted in the adult to the pineal gland. Crx (cone-rod homeobox), a downstream target gene of Otx2, showed a pineal expression...... the level of Otx2 mRNA appears to be independent of the photoneural input to the gland. Our results are consistent with the view that pineal expression of Otx2 is required for development and we hypothesize that it plays a role in the adult in controlling the expression of the cluster of genes...

  2. Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain

    Science.gov (United States)

    Huber, J. D.; Campos, C. R.; Mark, K. S.; Davis, T. P.

    2014-01-01

    Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1–6 h); however, brain region-specific increases in micro-glial activation suggest a potential for a central-mediated response. PMID:16199477

  3. Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis

    Science.gov (United States)

    Capurro, Alberto; Bodea, Liviu-Gabriel; Schaefer, Patrick; Luthi-Carter, Ruth; Perreau, Victoria M.

    2015-01-01

    The characterization of molecular changes in diseased tissues gives insight into pathophysiological mechanisms and is important for therapeutic development. Genome-wide gene expression analysis has proven valuable for identifying biological processes in neurodegenerative diseases using post mortem human brain tissue and numerous datasets are publically available. However, many studies utilize heterogeneous tissue samples consisting of multiple cell types, all of which contribute to global gene expression values, confounding biological interpretation of the data. In particular, changes in numbers of neuronal and glial cells occurring in neurodegeneration confound transcriptomic analyses, particularly in human brain tissues where sample availability and controls are limited. To identify cell specific gene expression changes in neurodegenerative disease, we have applied our recently published computational deconvolution method, population specific expression analysis (PSEA). PSEA estimates cell-type-specific expression values using reference expression measures, which in the case of brain tissue comprises mRNAs with cell-type-specific expression in neurons, astrocytes, oligodendrocytes and microglia. As an exercise in PSEA implementation and hypothesis development regarding neurodegenerative diseases, we applied PSEA to Parkinson's and Huntington's disease (PD, HD) datasets. Genes identified as differentially expressed in substantia nigra pars compacta neurons by PSEA were validated using external laser capture microdissection data. Network analysis and Annotation Clustering (DAVID) identified molecular processes implicated by differential gene expression in specific cell types. The results of these analyses provided new insights into the implementation of PSEA in brain tissues and additional refinement of molecular signatures in human HD and PD. PMID:25620908

  4. A study of ICAM expression in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Hoon; Lee, Seung Hoon; Hong, Seok Il [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1995-12-01

    The purpose of this study is to test the possibility of using sICAM-1 as a marker for follow-up of treatment. The micro-ELISA method was adopted. The brain stem gliomas showed positive results in 67%. Overall, 23% of brain tumors showed positive results. It is possible that we can use sICAM-1 as a marker for metastatic brain tumors, and measurement after radiation therapy is not reliable. 6 refs. (Author) (Author).

  5. Enhanced Expression of Aquaporin-9 in Rat Brain Edema Induced by Bacterial Lipopolysaccharides

    Institute of Scientific and Technical Information of China (English)

    Huaili WANG; Runming JIN; Peichao TIAN; Zhihong ZHUO

    2009-01-01

    To investigate the role of AQP9 in brain edema,the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined.Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals.Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection,with maximum value appearing at 12 h,which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals.The further correlation analysis revealed strong positive correlations among the brain water content,the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals.These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.

  6. IL-17A Synergizes with IFN-γ to Upregulate iNOS and NO Production and Inhibit Chlamydial Growth

    OpenAIRE

    Zhang, Yongci; Wang, Haiping; Ren, Jianyun; Tang, Xiaofei; Jing, Ye; Xing, Donghong; Zhao, Guosheng; Yao, Zhi; Yang, Xi; Bai, Hong

    2012-01-01

    IFN-γ-mediated inducible nitric oxide synthase (iNOS) expression is critical for controlling chlamydial infection through microbicidal nitric oxide (NO) production. Interleukin-17A (IL-17A), as a new proinflammatory cytokine, has been shown to play a protective role in host defense against Chlamydia muridarum (Cm) infection. To define the related mechanism, we investigated, in the present study, the effect of IL-17A on IFN-γ induced iNOS expression and NO production during Cm infection in vit...

  7. Ternary complex formation of Ino2p-Ino4p transcription factors and Apl2p adaptin beta subunit in yeast.

    Science.gov (United States)

    Nikawa, Jun-ichi; Yata, Masako; Motomura, Miki; Miyoshi, Nobutaka; Ueda, Tsuyoshi; Hisada, Daisuke

    2006-11-01

    Yeast Ino2p-Ino4p heterodimeric complex is well known as a transcriptional activator for the genes regulated by inositol and choline, such as the INO1 gene. Apl2p is a large subunit of the yeast adaptin complex, an adaptor complex required for the clathrin coat to bind to the membrane. We found that Ino2p, Ino4p, and Apl2p form a ternary complex. This interaction was initially observed in a yeast two-hybrid study and subsequently verified by co-immunoprecipitation. Ino2p and Ino4p bind to Apl2p in the same region of Apl2p, viz., at the middle part and the C-terminal part. Ino2p and Ino4p bind to Apl2p independently, but more strongly when both are present. Furthermore, a disruption of APL2 together with INO2 or INO4 rendered yeast cells sensitive to oxidative stress. INO2-APL2 double disruptants also showed growth inability in non-fermentable carbon sources, such as glycerol. These results indicate a genetic interaction between APL2, INO2 and INO4 and uncovere novel functions of the Ino2p-Ino4p-Apl2p complex in yeast. PMID:17090927

  8. Sex-biased gene expression in the developing brain: implications for autism spectrum disorders

    OpenAIRE

    Ziats, Mark N.; Rennert, Owen M.

    2013-01-01

    Abstract Autism spectrum disorders affect significantly more males than females. Understanding sex differences in normal human brain development may provide insight into the mechanism(s) underlying this disparity; however, studies of sex differences in brain development at the genomic level are lacking. Here, we report a re-analysis of sex-specific gene expression from a recent large transcriptomic study of normal human brain development, to determine whether sex-biased genes relate to specif...

  9. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

    DEFF Research Database (Denmark)

    Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E;

    2010-01-01

    Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and....../or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally and......(6266) (p <0.05), and stationary levels for Aqp1. Aqp1 and Aqp4 mRNA were stationary. This study indicates that Aqp4, but not Aqp1, may be of importance in the pathogenesis of cortical brain edema in mice with ALF....

  10. Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers.

    Science.gov (United States)

    Pramparo, Tiziano; Lombardo, Michael V; Campbell, Kathleen; Barnes, Cynthia Carter; Marinero, Steven; Solso, Stephanie; Young, Julia; Mayo, Maisi; Dale, Anders; Ahrens-Barbeau, Clelia; Murray, Sarah S; Lopez, Linda; Lewis, Nathan; Pierce, Karen; Courchesne, Eric

    2015-12-01

    Genetic mechanisms underlying abnormal early neural development in toddlers with Autism Spectrum Disorder (ASD) remain uncertain due to the impossibility of direct brain gene expression measurement during critical periods of early development. Recent findings from a multi-tissue study demonstrated high expression of many of the same gene networks between blood and brain tissues, in particular with cell cycle functions. We explored relationships between blood gene expression and total brain volume (TBV) in 142 ASD and control male toddlers. In control toddlers, TBV variation significantly correlated with cell cycle and protein folding gene networks, potentially impacting neuron number and synapse development. In ASD toddlers, their correlations with brain size were lost as a result of considerable changes in network organization, while cell adhesion gene networks significantly correlated with TBV variation. Cell cycle networks detected in blood are highly preserved in the human brain and are upregulated during prenatal states of development. Overall, alterations were more pronounced in bigger brains. We identified 23 candidate genes for brain maldevelopment linked to 32 genes frequently mutated in ASD. The integrated network includes genes that are dysregulated in leukocyte and/or postmortem brain tissue of ASD subjects and belong to signaling pathways regulating cell cycle G1/S and G2/M phase transition. Finally, analyses of the CHD8 subnetwork and altered transcript levels from an independent study of CHD8 suppression further confirmed the central role of genes regulating neurogenesis and cell adhesion processes in ASD brain maldevelopment. PMID:26668231

  11. Expression of nestin by neural cells in the adult rat and human brain.

    Directory of Open Access Journals (Sweden)

    Michael L Hendrickson

    Full Text Available Neurons and glial cells in the developing brain arise from neural progenitor cells (NPCs. Nestin, an intermediate filament protein, is thought to be expressed exclusively by NPCs in the normal brain, and is replaced by the expression of proteins specific for neurons or glia in differentiated cells. Nestin expressing NPCs are found in the adult brain in the subventricular zone (SVZ of the lateral ventricle and the subgranular zone (SGZ of the dentate gyrus. While significant attention has been paid to studying NPCs in the SVZ and SGZ in the adult brain, relatively little attention has been paid to determining whether nestin-expressing neural cells (NECs exist outside of the SVZ and SGZ. We therefore stained sections immunocytochemically from the adult rat and human brain for NECs, observed four distinct classes of these cells, and present here the first comprehensive report on these cells. Class I cells are among the smallest neural cells in the brain and are widely distributed. Class II cells are located in the walls of the aqueduct and third ventricle. Class IV cells are found throughout the forebrain and typically reside immediately adjacent to a neuron. Class III cells are observed only in the basal forebrain and closely related areas such as the hippocampus and corpus striatum. Class III cells resemble neurons structurally and co-express markers associated exclusively with neurons. Cell proliferation experiments demonstrate that Class III cells are not recently born. Instead, these cells appear to be mature neurons in the adult brain that express nestin. Neurons that express nestin are not supposed to exist in the brain at any stage of development. That these unique neurons are found only in brain regions involved in higher order cognitive function suggests that they may be remodeling their cytoskeleton in supporting the neural plasticity required for these functions.

  12. THE RELATIONSHIP BETWEEN PERITUMORAL BRAIN EDEMA AND VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION IN PATIENTS WITH MENINGIOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To determine whether VEGF plays a role in the development of peritumoral brain edema. Methods 50 meningioma patients and their VEGF expression were studied. We took a mono- clonal antibody from mouse to VEGF to stain the tumor cells, the vascular endothelial cells and the interstitial cells. The severity of brain edema was evaluated according to CT or MR scans by the following equation: edema index = Vtumor+edema/Vtumor. The relationship between VEGF expression and edema index was analyzed statisti- cally. Results VEGF was expressed in meningioma tumor cells, which is usually concentrated at the pe- ripheral sites of the tumor. There was a positive linear correlation between the expression and the brain edema index. Conclusion VEGF may play a role in the development of peritumoral brain edema in meningioma patient.

  13. GLUT3 Gene Expression is Critical for Embryonic Growth, Brain Development and Survival

    OpenAIRE

    Carayannopoulos, Mary O.; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U.

    2014-01-01

    Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression o...

  14. Ischemia Alters the Expression of Connexins in the Aged Human Brain

    OpenAIRE

    Taizen Nakase; Tetsuya Maeda; Yasuji Yoshida; Ken Nagata

    2009-01-01

    Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43) has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Sev...

  15. Impact of experience-dependent and -independent factors on gene expression in songbird brain

    OpenAIRE

    Drnevich, Jenny; Replogle, Kirstin L.; Lovell, Peter; Hahn, Thomas P; Johnson, Frank; Mast, Thomas G; Nordeen, Ernest; Nordeen, Kathy; Strand, Christy; London, Sarah E; Mukai, Motoko; Wingfield, John C.; Arnold, Arthur P.; Ball, Gregory F.; Brenowitz, Eliot A.

    2012-01-01

    Songbirds provide rich natural models for studying the relationships between brain anatomy, behavior, environmental signals, and gene expression. Under the Songbird Neurogenomics Initiative, investigators from 11 laboratories collected brain samples from six species of songbird under a range of experimental conditions, and 488 of these samples were analyzed systematically for gene expression by microarray. ANOVA was used to test 32 planned contrasts in the data, revealing the relative impact ...

  16. A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

    Science.gov (United States)

    Portales-Casamar, Elodie; Swanson, Douglas J; Liu, Li; de Leeuw, Charles N; Banks, Kathleen G; Ho Sui, Shannan J; Fulton, Debra L; Ali, Johar; Amirabbasi, Mahsa; Arenillas, David J; Babyak, Nazar; Black, Sonia F; Bonaguro, Russell J; Brauer, Erich; Candido, Tara R; Castellarin, Mauro; Chen, Jing; Chen, Ying; Cheng, Jason C Y; Chopra, Vik; Docking, T Roderick; Dreolini, Lisa; D'Souza, Cletus A; Flynn, Erin K; Glenn, Randy; Hatakka, Kristi; Hearty, Taryn G; Imanian, Behzad; Jiang, Steven; Khorasan-zadeh, Shadi; Komljenovic, Ivana; Laprise, Stéphanie; Liao, Nancy Y; Lim, Jonathan S; Lithwick, Stuart; Liu, Flora; Liu, Jun; Lu, Meifen; McConechy, Melissa; McLeod, Andrea J; Milisavljevic, Marko; Mis, Jacek; O'Connor, Katie; Palma, Betty; Palmquist, Diana L; Schmouth, Jean-François; Swanson, Magdalena I; Tam, Bonny; Ticoll, Amy; Turner, Jenna L; Varhol, Richard; Vermeulen, Jenny; Watkins, Russell F; Wilson, Gary; Wong, Bibiana K Y; Wong, Siaw H; Wong, Tony Y T; Yang, George S; Ypsilanti, Athena R; Jones, Steven J M; Holt, Robert A; Goldowitz, Daniel; Wasserman, Wyeth W; Simpson, Elizabeth M

    2010-09-21

    The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination "knockins" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type-specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies. PMID:20807748

  17. Expression of GFAP MRNA in rat hippocampus after whole-brain irradiation

    International Nuclear Information System (INIS)

    Objective: To discuss the role of GFAP in brain irradiation injury by observing the expression changes of GFAPmRNA in the hippocampus region of rat after whole-brain irradiation. Methods: The model was established in the rat after whole-brain irradiation with the single dose of 4 MeV electron beam. The dynamic expression of GFAPmRNA in the hippocampus was analyzed semi-quantitatively at different times (1 and 30 days) and doses (2 Gy, 10 Gy and 30 Gy) points with RT-PCR. Results: The level of GFAPmRNA was elevated significantly 1 day after whole-brain irradiation in 10 Gy and 30 Gy groups (P0.05). Conclusions: the up-regulation of GFAPmRNA is time and radiation dose dependent. GFAP plays an important role in protective and imparative mechanism of brain irradiation injury. (authors)

  18. Abnormal expressions of proliferating cell nuclear antigen and P27 protein in brain glioma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Both proliferating cell nuclear antigen and P27 protein are important factors to regulate cell cycle. While, the combination of them can provide exactly objective markers to evaluate prognosis of patients with brain glioma needs to be further studied based on pathological level.OBJECTIVE: To observe the expressions of proliferating cell nuclear antigen and P27 protein in both injured and normal brain glioma tissues and analyze the effect of them on onset and development of brain glioma.DESIGN: Case contrast observation.SETTING: Department of Neurosurgery, the Second Affiliated Hospital of Xi'an Jiaotong University.PARTICIPANTS: A total of 63 patients with brain glioma were selected from Department of Neurosurgery,the Second Affiliated Hospital of Xi'an Jiaotong University from July 1996 to June 2000. There were 38 males and 25 females and their ages ranged from 23 to 71 years. Based on pathological classification and grading standards of brain glioma, patients were divided into grade Ⅰ - tⅡ (n =30) and grade Ⅲ - Ⅳ (n =33). All cases received one operation but no radiotherapy and chemiotherapy before operation. Sample tissues were collected from tumor parenchyma. Non-neoplastic brain tissues were collected from another 12 non-tumor subjects who received craniocerebral trauma infra-decompression and regarded as the control group. There were 10 males and 2 females and their ages ranged from 16 to 54 years. The experiment had got confirmed consent from local ethic committee and the collection was provided confirmed consent from patients and their relatives. All samples were restained with HE staining so as to diagnose as the brain glioma.While, all patients with brain glioma received radiotherapy after operation and their survival periods were followed up.METHODS: Primary lesion wax of brain glioma was cut into serial sections and stained with S-P immunohistochemical staining. Brown substance which was observed in tumor nucleus was regarded as the

  19. Altered brain protein expression profiles are associated with molecular neurological dysfunction in the PKU mouse model.

    Science.gov (United States)

    Imperlini, Esther; Orrù, Stefania; Corbo, Claudia; Daniele, Aurora; Salvatore, Francesco

    2014-06-01

    Phenylketonuria (PKU), if not detected and treated in newborns, causes severe neurological dysfunction and cognitive and behavioral deficiencies. Despite the biochemical characterization of PKU, the molecular mechanisms underlying PKU-associated brain dysfunction remain poorly understood. The aim of this study was to gain insights into the pathogenesis of this neurological damage by analyzing protein expression profiles in brain tissue of Black and Tan BRachyury-PahEnu2 mice (a mouse model of PKU). We compared the cerebral protein expression of homozygous PKU mice with that of their heterozygous counterparts using two-dimensional difference gel electrophoresis analysis, and identified 21 differentially expressed proteins, four of which were over-expressed and 17 under-expressed. An in silico bioinformatic approach indicated that protein under-expression was related to neuronal differentiation and dendritic growth, and to such neurological disorders as progressive motor neuropathy and movement disorders. Moreover, functional annotation analyses showed that some identified proteins were involved in oxidative metabolism. To further investigate the proteins involved in the neurological damage, we validated two of the proteins that were most strikingly under-expressed, namely, Syn2 and Dpysl2, which are involved in synaptic function and neurotransmission. We found that Glu2/3 and NR1 receptor subunits were over-expressed in PKU mouse brain. Our results indicate that differential expression of these proteins may be associated with the processes underlying PKU brain dysfunction, namely, decreased synaptic plasticity and impaired neurotransmission. We identified a set of proteins whose expression is affected by hyperphenylalaninemia. We think that phenylketonuria (PKU) brain dysfunction also depends on reduced Syn2 and Dpysl2 levels, increased Glu2/3 and NR1 levels, and decreased Pkm, Ckb, Pgam1 and Eno1 levels. These findings finally confirm that alteration in synaptic

  20. Association of HIF- expression and cell apoptosis after traumatic brain injury in the rat

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To explore the expression of hypoxia inducible factor-1α (HIF-1~) and the correlation between HIF-1α and apoptosis after traumatic brain injury.Methods: Using experimental traumatic brain injury in the rats, the expression of HIF-1α was studied by immunohisto-chemistry in cerebral tissue, apoptotic cell death was evaluated with TUNEL (transferase-mediated XdUTP nick end labeling ), and double-labeled immunohistochemistry and TUNEL methods were used to investigate the relationship between HIF-1α and apoptosis.Results: There was remarkable difference in the expression of HIF-1α between the experimental groups and the control groups (P < 0.01), in the experimental groups,the expression of HIF-1α at 48 hours was highest; the evidence of apoptotic cell death after experimental traumatic brain injury was found by TUNEL; the apoptotic percentage increased or decreased according to the changes of the positive expression of HIF-1α (r = 0.99).Conclusions: The results suggest that secondary brain ischemia plays a crucial role in apoptotic cell death after traumatic brain injury; HIF-1α can prompt apoptotic cell death after experimental traumatic brain injury.e expres

  1. Spontaneous Wheel Running Exercise Induces Brain Recovery via Neurotrophin-3 Expression Following Experimental Traumatic Brain Injury in Rats.

    Science.gov (United States)

    Koo, Hyun Mo; Lee, Sun Min; Kim, Min Hee

    2013-09-01

    [Purpose] The aim of the present study was to investigate the expression of neurotrophin-3 (NT-3) after applying spontaneous wheel running exercises (SWR) after experimental traumatic brain injury (TBI). [Subjects and Methods] Thirty male Sprague-Dawley rats were divided into 3 groups; 20 rats were subjected to controlled cortical impact for TBI, and then, animals were randomly collected from the SWR group and subjected to wheel running exercise for 3 weeks. Ten rats were not subjected to any injury or running exercise to compare with the effect of TBI and SWR. Immunohistochemistry, Western blotting, skilled ladder rung walking test, and 2,3,5-triphenyltetrazolium chloride staining analysis for the evaluation of NT-3 expression were used to assess brain damage and recovery. [Results] The TBI-induced decrease in NT-3 expression was recovered by wheel running exercise. Moreover, decreased ischemic volume and progressive neurobehavioral outcome were observed in the SWR group. [Conclusion] Spontaneous running exercise promotes brain recovery and motor function through an increase in expression of NT-3. PMID:24259924

  2. Brain expressed microRNAs implicated in schizophrenia etiology

    DEFF Research Database (Denmark)

    Hansen, Thomas; Olsen, Line; Lindow, Morten;

    2007-01-01

    Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors. I...

  3. India-based Neutrino Observatory(INO): A Status Report

    International Nuclear Information System (INIS)

    We present a status report on the proposed India-based Neutrino Observatory (INO). Various aspects of the INO project such as its location, the present status of the detector development, physics goals and simulation studies are discussed briefly. In particular we focus on physics studies possible with an iron calorimeter detector (ICAL) and the logistics of constructing this detector at INO. Such a detector would make precision measurements of neutrino oscillation parameters with atmospheric neutrinos in the first phase with the possibility of acting as a far-end detector of a future neutrino factory or beta beam.

  4. India-based Neutrino Observatory(INO): A Status Report

    Science.gov (United States)

    Murthy, M. V. N.

    2011-11-01

    We present a status report on the proposed India-based Neutrino Observatory (INO). Various aspects of the INO project such as its location, the present status of the detector development, physics goals and simulation studies are discussed briefly. In particular we focus on physics studies possible with an iron calorimeter detector (ICAL) and the logistics of constructing this detector at INO. Such a detector would make precision measurements of neutrino oscillation parameters with atmospheric neutrinos in the first phase with the possibility of acting as a far-end detector of a future neutrino factory or beta beam.

  5. Expression profile of the cadherin family in the developing Drosophila brain.

    Science.gov (United States)

    Fung, Siaumin; Wang, Fay; Chase, Maretta; Godt, Dorothea; Hartenstein, Volker

    2008-01-20

    The Drosophila genome encodes 17 members of the cadherin family of adhesion molecules, which in vertebrates has been implicated in patterning the nervous system through cell and axon sorting. With only a few exceptions all cadherins show widespread expression in the larval brain. What expression patterns have in common is that 1) they are global, in the sense that all lineages of the central brain or optic lobe, or both, show expression; and 2) expression is stage-specific: some cadherins are expressed only in primary neurons (located closest to the neuropile), others in early secondary neurons (near the brain surface), or primaries plus late secondaries. The Fat-like cadherins, Fat and Dachsous, as well as Cad96Ca and Cad74A, are expressed in the epithelial optic lobe anlagen, which matches the widespread epithelial expression of these molecules in the embryo. DE-cadherin is restricted to immature secondary neurons and glia; by contrast, DN-cadherin, Flamingo, Cad87A, Cad99C, and Calsyntenin-1 appear in differentiating primary neurons and, at a later stage, some or all secondary neurons. Cad87A is strongly enriched apically in epithelia and in neuronal dendrites. Fat-like, Cad86C, Cad88C, Cad89D, and Dret are expressed ubiquitously in embryonic and larval brains at low or moderate levels. We conclude from this analysis that cadherins are likely to play a role in 'generic' neural functions, such as neurite fasciculation, branching, and synapse formation. PMID:18041774

  6. Infants' Emerging Sensitivity to Emotional Body Expressions: Insights from Asymmetrical Frontal Brain Activity

    Science.gov (United States)

    Missana, Manuela; Grossmann, Tobias

    2015-01-01

    Sensitive responding to others' emotional body expressions is an essential social skill in humans. Using event-related brain potentials, it has recently been shown that the ability to discriminate between emotional body expressions develops between 4 and 8 months of age. However, it is not clear whether the perception of emotional body…

  7. Teneurin-1 is expressed in interconnected regions of the developing brain and is processed in vivo

    Directory of Open Access Journals (Sweden)

    Leachman Nathaniel T

    2008-03-01

    Full Text Available Abstract Background Teneurins are a unique family of transmembrane proteins conserved from C. elegans and D. melanogaster to mammals. In vertebrates there are four paralogs (teneurin-1 to -4, all of which are expressed prominently in the developing central nervous system. Results Analysis of teneurin-1 expression in the developing chick brain by in situ hybridization and immunohistochemistry defined a unique, distinct expression pattern in interconnected regions of the brain. Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information. Based on these expression patterns, we suspect a role for teneurins in neuronal connectivity. In contrast to the cell-surface staining of the antibody against the extracellular domain, an antibody recognizing the intracellular domain revealed nuclear staining in subpopulations of neurons and in undifferentiated mesenchyme. Western blot analysis of brain lysates showed the presence of N-terminal fragments of teneurin-1 containing the intracellular domain indicating that proteolytic processing occurs. Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells. Conclusion Teneurin-1 and -2 are expressed by distinct interconnected populations of neurons in the developing central nervous system. Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.

  8. Teneurin-1 is expressed in interconnected regions of the developing brain and is processed in vivo

    Science.gov (United States)

    Kenzelmann, Daniela; Chiquet-Ehrismann, Ruth; Leachman, Nathaniel T; Tucker, Richard P

    2008-01-01

    Background Teneurins are a unique family of transmembrane proteins conserved from C. elegans and D. melanogaster to mammals. In vertebrates there are four paralogs (teneurin-1 to -4), all of which are expressed prominently in the developing central nervous system. Results Analysis of teneurin-1 expression in the developing chick brain by in situ hybridization and immunohistochemistry defined a unique, distinct expression pattern in interconnected regions of the brain. Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information. Based on these expression patterns, we suspect a role for teneurins in neuronal connectivity. In contrast to the cell-surface staining of the antibody against the extracellular domain, an antibody recognizing the intracellular domain revealed nuclear staining in subpopulations of neurons and in undifferentiated mesenchyme. Western blot analysis of brain lysates showed the presence of N-terminal fragments of teneurin-1 containing the intracellular domain indicating that proteolytic processing occurs. Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells. Conclusion Teneurin-1 and -2 are expressed by distinct interconnected populations of neurons in the developing central nervous system. Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus. PMID:18366734

  9. Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

    Directory of Open Access Journals (Sweden)

    Patrick N Harter

    Full Text Available The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.

  10. Upregulated gene expression of local brain-derived neurotrophic factor and nerve growth factor after intracisternal administration of marrow stromal cells in rats with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    胡德志; 周良辅; 朱剑虹; 毛颖; 吴雪海

    2005-01-01

    Objective: To examine the effects of rat marrow stromal cells (rMSCs) on gene expression of local brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) after injection of rMSCs into Cistern Magnum of adult rats subjected to traumatic brain injury(TBI).Results: Group cell transplantation had higher BDNF and NGF gene expressions than Group saline control during a period of less than 3 weeks (P<0.05).Conclusions: rMSCs transplantation via Cistern Magnum in rats subjected to traumatic brain injury can enhance expressions of local brain NGF and BDNF to a certain extent.

  11. Deletion of UCP2 in iNOS deficient mice reduces the severity of the disease during experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Caroline Aheng

    Full Text Available Uncoupling protein 2 is a member of the mitochondrial anion carrier family that is widely expressed in neurons and the immune cells of humans. Deletion of Ucp2 gene in mice pre-activates the immune system leading to higher resistance toward infection and to an increased susceptibility to develop chronic inflammatory diseases as previously exemplified with the Experimental Autoimmune Encephalomyelitis (EAE, a mouse model for multiple sclerosis. Given that oxidative stress is enhanced in Ucp2-/- mice and that nitric oxide (NO also plays a critical function in redox balance and in chronic inflammation, we generated mice deficient for both Ucp2 and iNos genes and submitted them to EAE. Mice lacking iNos gene exhibited the highest clinical score (3.4+/-0.5 p<0.05. Surprisingly, mice deficient for both genes developed milder disease with reduced immune cell infiltration, cytokines and ROS production as compared to iNos-/- mice.

  12. Luteolin, a bioflavonoid inhibits azoxymethane-induced colon carcinogenesis: Involvement of iNOS and COX-2

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Pandurangan

    2014-01-01

    Full Text Available Colon cancer (CRC is a serious health problem through worldwide. Development of novel drug without side effect for this cancer was crucial. Luteolin (LUT, a bioflavonoid has many beneficial effects such as antioxidant, anti-inflammatory, anti-proliferative properties. Azoxymethane (AOM, a derivative of 1, 2-Dimethyl hydrazine (DMH was used for the induction of CRC in Balb/C mice. CRC was induced by intraperitoneal injection of AOM to mice at the dose of 15 mg/body kg weight for 3 weeks. Mouse was treated with LUT at the dose of 1.2 mg/body kg weight orally until end of the experiment. The expression of inducible nitric oxide synthase (iNOS and cyclooxygense (COX-2 were analyzed by RT-PCR and immunohistochemistry. The expressions of iNOS and COX-2 were increased in the case of AOM induction. Administration of LUT effectively reduced the expressions of iNOS and COX-2. The present study revealed that, LUT suppresses both iNOS and COX-2 expressions and act as an anti-inflammatory role against CRC.

  13. Expression of the Astrocyte Water Channel Aquaporin-4 in the Mouse Brain.

    Science.gov (United States)

    Hubbard, Jacqueline A; Hsu, Mike S; Seldin, Marcus M; Binder, Devin K

    2015-01-01

    Aquaporin-4 (AQP4) is a bidirectional water channel that is found on astrocytes throughout the central nervous system. Expression is particularly high around areas in contact with cerebrospinal fluid, suggesting that AQP4 plays a role in fluid exchange between the cerebrospinal fluid compartments and the brain. Despite its significant role in the brain, the overall spatial and region-specific distribution of AQP4 has yet to be fully characterized. In this study, we used Western blotting and immunohistochemical techniques to characterize AQP4 expression and localization throughout the mouse brain. We observed AQP4 expression throughout the forebrain, subcortical areas, and brainstem. AQP4 protein levels were highest in the cerebellum with lower expression in the cortex and hippocampus. We found that AQP4 immunoreactivity was profuse on glial cells bordering ventricles, blood vessels, and subarachnoid space. Throughout the brain, AQP4 was expressed on astrocytic end-feet surrounding blood vessels but was also heterogeneously expressed in brain tissue parenchyma and neuropil, often with striking laminar specificity. In the cerebellum, we showed that AQP4 colocalized with the proteoglycan brevican, which is synthesized by and expressed on cerebellar astrocytes. Despite the high abundance of AQP4 in the cerebellum, its functional significance has yet to be investigated. Given the known role of AQP4 in synaptic plasticity in the hippocampus, the widespread and region-specific expression pattern of AQP4 suggests involvement not only in fluid balance and ion homeostasis but also local synaptic plasticity and function in distinct brain circuits. PMID:26489685

  14. Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains.

    Science.gov (United States)

    Ahmed-Jushuf, Fiyyaz; Jiwa, Nadim S; Arwani, Anum S; Foot, Peter; Bridges, Leslie R; Kalaria, Raj N; Esiri, Margaret M; Hainsworth, Atticus H

    2016-06-01

    Vascular myocytes are central to brain aging. Small vessel disease (SVD; arteriolosclerosis) is a widespread cause of lacunar stroke and vascular dementia and is characterized by fibrosis and depletion of vascular myocytes in small penetrating arteries. Vascular endothelial growth factor (VEGF) is associated with brain aging, and Immunolabeling for vascular endothelial growth factor receptor 2 (VEGFR2) is a potent determinant of cell fate. Here, we tested whether VEGFR2 in vascular myocytes is associated with older age and SVD in human brain. Immunolabeling for VEGFR2 in deep gray matter was assessed in older people with or without moderate-severe SVD or in younger people without brain pathology or with a monogenic form of SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). All cases were without Alzheimer's disease pathology. Myocyte VEGFR2 was associated with increasing age (p = 0.0026) but not with SVD pathology or with sclerotic index or blood vessel density. We conclude that VEGFR2 is consistently expressed in small artery myocytes of older people and may mediate effects of VEGF on brain vascular aging. PMID:27143427

  15. GFAPδ expression in glia of the developmental and adolescent mouse brain.

    Directory of Open Access Journals (Sweden)

    Carlyn Mamber

    Full Text Available Glial fibrillary acidic protein (GFAP is the major intermediate filament (IF protein in astrocytes. In the human brain, GFAP isoforms have unique expression patterns, which indicate that they play distinct functional roles. One isoform, GFAPδ, is expressed by proliferative radial glia in the developing human brain. In the adult human, GFAPδ is a marker for neural stem cells. However, it is unknown whether GFAPδ marks the same population of radial glia and astrocytes in the developing mouse brain as it does in the developing human brain. This study characterizes the expression pattern of GFAPδ throughout mouse embryogenesis and into adolescence. Gfapδ transcripts are expressed from E12, but immunohistochemistry shows GFAPδ staining only from E18. This finding suggests a translational uncoupling. GFAPδ expression increases from E18 to P5 and then decreases until its expression plateaus around P25. During development, GFAPδ is expressed by radial glia, as denoted by the co-expression of markers like vimentin and nestin. GFAPδ is also expressed in other astrocytic populations during development. A similar pattern is observed in the adolescent mouse, where GFAPδ marks both neural stem cells and mature astrocytes. Interestingly, the Gfapδ/Gfapα transcript ratio remains stable throughout development as well as in primary astrocyte and neurosphere cultures. These data suggest that all astroglia cells in the developing and adolescent mouse brain express GFAPδ, regardless of their neurogenic capabilities. GFAPδ may be an integral component of all mouse astrocytes, but it is not a specific neural stem cell marker in mice as it is in humans.

  16. Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain.

    Directory of Open Access Journals (Sweden)

    Melissa A Fowler

    Full Text Available The canonical transient receptor potential (TRPC channels are a family of non-selective cation channels that are activated by increases in intracellular Ca(2+ and G(q/phospholipase C-coupled receptors. We used quantitative real-time PCR, in situ hybridization, immunoblots and patch-clamp recording from several brain regions to examine the expression of the predominant TRPC channels in the rodent brain. Quantitative real-time PCR of the seven TRPC channels in the rodent brain revealed that TRPC4 and TRPC5 channels were the predominant TRPC subtypes in the adult rat brain. In situ hybridization histochemistry and immunoblotting further resolved a dense corticolimbic expression of the TRPC4 and TRPC5 channels. Total protein expression of HIP TRPC4 and 5 proteins increased throughout development and peaked late in adulthood (6-9 weeks. In adults, TRPC4 expression was high throughout the frontal cortex, lateral septum (LS, pyramidal cell layer of the hippocampus (HIP, dentate gyrus (DG, and ventral subiculum (vSUB. TRPC5 was highly expressed in the frontal cortex, pyramidal cell layer of the HIP, DG, and hypothalamus. Detailed examination of frontal cortical layer mRNA expression indicated TRPC4 mRNA is distributed throughout layers 2-6 of the prefrontal cortex (PFC, motor cortex (MCx, and somatosensory cortex (SCx. TRPC5 mRNA expression was concentrated specifically in the deep layers 5/6 and superficial layers 2/3 of the PFC and anterior cingulate. Patch-clamp recording indicated a strong metabotropic glutamate-activated cation current-mediated depolarization that was dependent on intracellular Ca(2+and inhibited by protein kinase C in brain regions associated with dense TRPC4 or 5 expression and absent in regions lacking TRPC4 and 5 expression. Overall, the dense corticolimbic expression pattern suggests that these Gq/PLC coupled nonselective cation channels may be involved in learning, memory, and goal-directed behaviors.

  17. Spontaneous Wheel Running Exercise Induces Brain Recovery via Neurotrophin-3 Expression Following Experimental Traumatic Brain Injury in Rats

    OpenAIRE

    Koo, Hyun Mo; Lee, Sun Min; Kim, Min Hee

    2013-01-01

    [Purpose] The aim of the present study was to investigate the expression of neurotrophin-3 (NT-3) after applying spontaneous wheel running exercises (SWR) after experimental traumatic brain injury (TBI). [Subjects and Methods] Thirty male Sprague-Dawley rats were divided into 3 groups; 20 rats were subjected to controlled cortical impact for TBI, and then, animals were randomly collected from the SWR group and subjected to wheel running exercise for 3 weeks. Ten rats were not subjected to any...

  18. Metal ion toxins and brain aquaporin-4 expression: an overview

    OpenAIRE

    Adriana eXimenes-Da-Silva

    2016-01-01

    Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS) results in changes in blood-brain barrier (BBB) permeability, as well as triggering microglia a...

  19. Metal Ion Toxins and Brain Aquaporin-4 Expression: An Overview

    OpenAIRE

    Ximenes-da-Silva, Adriana

    2016-01-01

    Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS) results in changes in blood-brain barrier (BBB) permeability, as well as triggering microglia a...

  20. Different brain networks underlying the acquisition and expression of contextual fear conditioning: a metabolic mapping study.

    Science.gov (United States)

    González-Pardo, H; Conejo, N M; Lana, G; Arias, J L

    2012-01-27

    The specific brain regions and circuits involved in the acquisition and expression of contextual fear conditioning are still a matter of debate. To address this issue, regional changes in brain metabolic capacity were mapped during the acquisition and expression of contextual fear conditioning using cytochrome oxidase (CO) quantitative histochemistry. In comparison with a group briefly exposed to a conditioning chamber, rats that received a series of randomly presented footshocks in the same conditioning chamber (fear acquisition group) showed increased CO activity in anxiety-related brain regions like the ventral periaqueductal gray, the ventral hippocampus, the lateral habenula, the mammillary bodies, and the laterodorsal thalamic nucleus. Another group received randomly presented footshocks, and it was re-exposed to the same conditioning chamber one week later (fear expression group). The conditioned group had significantly higher CO activity as compared with the matched control group in the following brain regions: the ventral periaqueductal gray, the central and lateral nuclei of the amygdala, and the bed nucleus of the stria terminalis. In addition, analysis of functional brain networks using interregional CO activity correlations revealed different patterns of functional connectivity between fear acquisition and fear expression groups. In particular, a network comprising the ventral hippocampus and amygdala nuclei was found in the fear acquisition group, whereas a closed reciprocal dorsal hippocampal network was detected in the fear expression group. These results suggest that contextual fear acquisition and expression differ as regards to the brain networks involved, although they share common brain regions involved in fear, anxiety, and defensive behavior. PMID:22173014

  1. Chronological changes in microRNA expression in the developing human brain.

    Directory of Open Access Journals (Sweden)

    Michael P Moreau

    Full Text Available MicroRNAs (miRNAs are endogenously expressed noncoding RNA molecules that are believed to regulate multiple neurobiological processes. Expression studies have revealed distinct temporal expression patterns in the developing rodent and porcine brain, but comprehensive profiling in the developing human brain has not been previously reported.We performed microarray and TaqMan-based expression analysis of all annotated mature miRNAs (miRBase 10.0 as well as 373 novel, predicted miRNAs. Expression levels were measured in 48 post-mortem brain tissue samples, representing gestational ages 14-24 weeks, as well as early postnatal and adult time points.Expression levels of 312 miRNAs changed significantly between at least two of the broad age categories, defined as fetal, young, and adult.We have constructed a miRNA expression atlas of the developing human brain, and we propose a classification scheme to guide future studies of neurobiological function.

  2. Personality Trait and Facial Expression Filter-Based Brain-Computer Interface

    OpenAIRE

    Seongah Chin; Chung-Yeon Lee

    2013-01-01

    In this paper, we present technical approaches that bridge the gap in the research related to the use of brain‐computer interfaces for entertainment and facial expressions. Such facial expressions that reflect an individual’s personal traits can be used to better realize artificial facial expressions in a gaming environment based on a brain‐computer interface. First, an emotion extraction filter is introduced in order to classify emotions on the basis of the users’ brain signals in real time....

  3. Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

    OpenAIRE

    Sato Wataru; Toichi Motomi; Uono Shota; Kochiyama Takanori

    2012-01-01

    Abstract Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear ...

  4. Detecting positive darwinian selection in brain-expressed genes during human evolution

    Institute of Scientific and Technical Information of China (English)

    QI XueBin; Alice A. LIN; Luca L. CAVALLI-SFORZA; WANG Jun; SU Bing; YANG Su; ZHENG HongKun; WANG YinQiu; LIAO ChengHong; LIU Ying; CHEN XiaoHua; SHI Hong; YU XiaoJing

    2007-01-01

    To understand the genetic basis that underlies the phenotypic divergence between human and nonhuman primates, we screened a total of 7176 protein-coding genes expressed in the human brain and compared them with the chimpanzee orthologs to identify genes that show evidence of rapid evolution in the human lineage. Our results showed that the nonsynonymous/synonymous substitution (Ka/Ks) ratio for genes expressed in the brain of human and chimpanzee is 0.3854, suggesting that the brain-expressed genes are under functional constraint. The X-linked human brain-expressed genes evolved more rapidly than autosomal ones. We further dissected the molecular evolutionary patterns of 34 candidate genes by sequencing representative primate species to identify lineage-specific adaptive evolution. Fifteen out of the 34 candidate genes showed evidence of positive Darwinian selection in human and/or chimpanzee lineages. These genes are predicted to play diverse functional roles in embryonic development, spermatogenesis and male fertility, signal transduction, sensory nociception, and neural function. This study together with others demonstrated the usefulness and power of phylogenetic comparison of multiple closely related species in detecting lineage-specific adaptive evolution, and the identification of the positively selected brain-expressed genes may add new knowledge to the understanding of molecular mechanism of human origin.

  5. Multiple faces of pain: effects of chronic pain on the brain regulation of facial expression.

    Science.gov (United States)

    Vachon-Presseau, Etienne; Roy, Mathieu; Woo, Choong-Wan; Kunz, Miriam; Martel, Marc-Olivier; Sullivan, Michael J; Jackson, Philip L; Wager, Tor D; Rainville, Pierre

    2016-08-01

    Pain behaviors are shaped by social demands and learning processes, and chronic pain has been previously suggested to affect their meaning. In this study, we combined functional magnetic resonance imaging with in-scanner video recording during thermal pain stimulations and use multilevel mediation analyses to study the brain mediators of pain facial expressions and the perception of pain intensity (self-reports) in healthy individuals and patients with chronic back pain (CBP). Behavioral data showed that the relation between pain expression and pain report was disrupted in CBP. In both patients with CBP and healthy controls, brain activity varying on a trial-by-trial basis with pain facial expressions was mainly located in the primary motor cortex and completely dissociated from the pattern of brain activity varying with pain intensity ratings. Stronger activity was observed in CBP specifically during pain facial expressions in several nonmotor brain regions such as the medial prefrontal cortex, the precuneus, and the medial temporal lobe. In sharp contrast, no moderating effect of chronic pain was observed on brain activity associated with pain intensity ratings. Our results demonstrate that pain facial expressions and pain intensity ratings reflect different aspects of pain processing and support psychosocial models of pain suggesting that distinctive mechanisms are involved in the regulation of pain behaviors in chronic pain. PMID:27411160

  6. Novel microRNAs differentially expressed during aging in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Sachi Inukai

    Full Text Available MicroRNAs (miRNAs are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 558 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since many mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that also function during aging in the human brain.

  7. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  8. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  9. Altered brain protein expression profiles are associated with molecular neurological dysfunction in the PKU mouse model

    OpenAIRE

    Imperlini, Esther; Orrù, Stefania; Corbo, Claudia; Daniele, Aurora; Salvatore, Francesco

    2014-01-01

    Phenylketonuria (PKU), if not detected and treated in newborns, causes severe neurological dysfunction and cognitive and behavioral deficiencies. Despite the biochemical characterization of PKU, the molecular mechanisms underlying PKU-associated brain dysfunction remain poorly understood. The aim of this study was to gain insights into the pathogenesis of this neurological damage by analyzing protein expression profiles in brain tissue of Black and Tan BRachyury-PahEnu2 mice (a mouse model of...

  10. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    OpenAIRE

    Shengxiu Li; Guoqiang Sun; Kiyohito Murai; Peng Ye; Yanhong Shi

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analo...

  11. Brain expressed microRNAs implicated in schizophrenia etiology

    DEFF Research Database (Denmark)

    Hansen, Thomas; Olsen, Line; Lindow, Morten;

    2007-01-01

    Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors....... Indeed, the growing understanding of the regulatory properties and pleiotropic effects that miRNA have on molecular and cellular mechanisms, suggests that alterations in the interactions between miRNAs and their mRNA targets may contribute to phenotypic variation....

  12. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    Directory of Open Access Journals (Sweden)

    José Jaime Herrera-Pérez

    2013-01-01

    Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

  13. Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Sato Wataru

    2012-08-01

    Full Text Available Abstract Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD. However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI. Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG, fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG. Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. Conclusions These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

  14. Impact of experience-dependent and -independent factors on gene expression in songbird brain.

    Science.gov (United States)

    Drnevich, Jenny; Replogle, Kirstin L; Lovell, Peter; Hahn, Thomas P; Johnson, Frank; Mast, Thomas G; Nordeen, Ernest; Nordeen, Kathy; Strand, Christy; London, Sarah E; Mukai, Motoko; Wingfield, John C; Arnold, Arthur P; Ball, Gregory F; Brenowitz, Eliot A; Wade, Juli; Mello, Claudio V; Clayton, David F

    2012-10-16

    Songbirds provide rich natural models for studying the relationships between brain anatomy, behavior, environmental signals, and gene expression. Under the Songbird Neurogenomics Initiative, investigators from 11 laboratories collected brain samples from six species of songbird under a range of experimental conditions, and 488 of these samples were analyzed systematically for gene expression by microarray. ANOVA was used to test 32 planned contrasts in the data, revealing the relative impact of different factors. The brain region from which tissue was taken had the greatest influence on gene expression profile, affecting the majority of signals measured by 18,848 cDNA spots on the microarray. Social and environmental manipulations had a highly variable impact, interpreted here as a manifestation of paradoxical "constitutive plasticity" (fewer inducible genes) during periods of enhanced behavioral responsiveness. Several specific genes were identified that may be important in the evolution of linkages between environmental signals and behavior. The data were also analyzed using weighted gene coexpression network analysis, followed by gene ontology analysis. This revealed modules of coexpressed genes that are also enriched for specific functional annotations, such as "ribosome" (expressed more highly in juvenile brain) and "dopamine metabolic process" (expressed more highly in striatal song control nucleus area X). These results underscore the complexity of influences on neural gene expression and provide a resource for studying how these influences are integrated during natural experience. PMID:23045667

  15. Homogentisate 1,2 dioxygenase is expressed in brain: implications in alkaptonuria.

    Science.gov (United States)

    Bernardini, Giulia; Laschi, Marcella; Geminiani, Michela; Braconi, Daniela; Vannuccini, Elisa; Lupetti, Pietro; Manetti, Fabrizio; Millucci, Lia; Santucci, Annalisa

    2015-09-01

    Alkaptonuria is an ultra-rare autosomal recessive disease developed from the lack of homogentisate 1,2-dioxygenase (HGD) activity, causing an accumulation in connective tissues of homogentisic acid (HGA) and its oxidized derivatives in polymerized form. The deposition of ochronotic pigment has been so far attributed to homogentisic acid produced by the liver, circulating in the blood, and accumulating locally. In the present paper, we report the expression of HGD in the brain. Mouse and human brain tissues were positively tested for HGD gene expression by western blotting. Furthermore, HGD expression was confirmed in human neuronal cells that also revealed the presence of six HGD molecular species. Moreover, once cultured in HGA excess, human neuronal cells produced ochronotic pigment and amyloid. Our findings indicate that alkaptonuric brain cells produce the ochronotic pigment in loco and this may contribute to induction of neurological complications. PMID:25762405

  16. Ischemia Alters the Expression of Connexins in the Aged Human Brain

    Directory of Open Access Journals (Sweden)

    Taizen Nakase

    2009-01-01

    Full Text Available Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43 has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Seven samples, sectioned after brain embolic stroke, were used for the analysis. Data, evaluated semiquantitatively by computer-assisted densitometry, was compared between the intact hemisphere and ischemic lesions. The results showed that the coexpression of Cx32 and Cx45 with neuronal markers was significantly increased in ischemic lesions. Cx43 expression was significantly increased in the colocalization with astrocytes and relatively increased in the colocalization with neuronal marker in ischemic lesions. Therefore, Cx32, Cx43, and Cx45 may respond differently to ischemic insult in terms of neuroprotection.

  17. Effect of naloxone hydrochloride on c-fos protein expression in brain and plasma beta-endorphin level in rats with diffuse brain injury and secondary brain insult

    Directory of Open Access Journals (Sweden)

    Jun-jie JING

    2012-09-01

    Full Text Available Objective To observe the changes of c-fos protein expression in brain and beta-endorphin (β-EP level in blood plasma in rats with diffuse brain injury (DBI and secondary brain insult (SBI after intraperitoneal injection of naloxone hydrochloride, and explore the role of c-fos andβ-EP in development of SBI in rats. Methods Seventy health male SD rats were enrolled in the present study and randomly divided into group A (intraperitoneally injected with 0.9% saline after DBI and SBI model was reproduced, group B (injected intraperitoneally with 1.0mg/kg naloxone hydrochloride after DBI and SBI model was reproduced, and group C (intraperitoneally injected with 1.0mg/kg naloxone hydrochloride after DBI and before SBI model was reproduced. The animals were sacrificed 3, 24 and 48 hours after injury, and the number of c-fos positive cells in brain and content of β-EP in blood plasma were determined by immunohistochemistry and radioimmunoassay respectively, the water content and number of injured neurons in brain tissue were measured by pathomorphological observation of the brain tissue. Results No significant difference was observed between group B and C for all the detection parameters. In group B and C, the water content in brain tissue at 3h and 24h was found to be decreased, while the number of injured neurons at 24h and 48h increased, number of c-fos positive cells in brain at 3h, 24h and 48h decreased, and content of β-EP in blood plasma at 3h and 24h decreased when compared with group A(P < 0.05. Conclusion Naloxone hydrochloride could decrease the c-fos expression in brain and β-EP level in blood plasma, alleviate the nerve injury, and protect neural function. The therapeutic effect of naloxone administered either after DBI and SBI or after DBI and before SBI was similar.

  18. Homocysteine homeostasis and betaine-homocysteine S-methyltransferase expression in the brain of hibernating bats.

    Directory of Open Access Journals (Sweden)

    Yijian Zhang

    Full Text Available Elevated homocysteine is an important risk factor that increases cerebrovascular and neurodegenerative disease morbidity. In mammals, B vitamin supplementation can reduce homocysteine levels. Whether, and how, hibernating mammals, that essentially stop ingesting B vitamins, maintain homocysteine metabolism and avoid cerebrovascular impacts and neurodegeneration remain unclear. Here, we compare homocysteine levels in the brains of torpid bats, active bats and rats to identify the molecules involved in homocysteine homeostasis. We found that homocysteine does not elevate in torpid brains, despite declining vitamin B levels. At low levels of vitamin B6 and B12, we found no change in total expression level of the two main enzymes involved in homocysteine metabolism (methionine synthase and cystathionine β-synthase, but a 1.85-fold increase in the expression of the coenzyme-independent betaine-homocysteine S-methyltransferase (BHMT. BHMT expression was observed in the amygdala of basal ganglia and the cerebral cortex where BHMT levels were clearly elevated during torpor. This is the first report of BHMT protein expression in the brain and suggests that BHMT modulates homocysteine in the brains of hibernating bats. BHMT may have a neuroprotective role in the brains of hibernating mammals and further research on this system could expand our biomedical understanding of certain cerebrovascular and neurodegenerative disease processes.

  19. Expression of Glutamatergic Genes in Healthy Humans across 16 Brain Regions; Altered Expression in the Hippocampus after Chronic Exposure to Alcohol or Cocaine

    OpenAIRE

    Enoch, Mary-Anne; Rosser, Alexandra A.; Zhou, Zhifeng; Mash, Deborah C; Yuan, Qiaoping; Goldman, David

    2014-01-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus.

  20. Whole brain expression of bipolar disorder associated genes: structural and genetic analyses.

    Directory of Open Access Journals (Sweden)

    Michael J McCarthy

    Full Text Available Studies of bipolar disorder (BD suggest a genetic basis of the illness that alters brain function and morphology. In recent years, a number of genetic variants associated with BD have been identified. However, little is known about the associated genes, or brain circuits that rely upon their function. Using an anatomically comprehensive survey of the human transcriptome (The Allen Brain Atlas, we mapped the expression of 58 genes with suspected involvement in BD based upon their relationship to SNPs identified in genome wide association studies (GWAS. We then conducted a meta-analysis of structural MRI studies to identify brain regions that are abnormal in BD. Of 58 BD associated genes, 22 had anatomically distinct expression patterns that could be categorized into one of three clusters (C1-C3. Brain regions with the highest and lowest expression of these genes did not overlap strongly with anatomical sites identified as abnormal by structural MRI except in the parahippocampal gyrus, the inferior/superior temporal gyrus and the cerebellar vermis, regions where overlap was significant. Using the 22 genes in C1-C3 as reference points, additional genes with correlated expression patterns were identified and organized into sets based on similarity. Further analysis revealed that five of these gene sets were significantly associated with BD, suggesting that anatomical expression profile is correlated with genetic susceptibility to BD, particularly for genes in C2. Our data suggest that expression profiles of BD-associated genes do not explain the majority of structural abnormalities observed in BD, but may be useful in identifying new candidate genes. Our results highlight the complex neuroanatomical basis of BD, and reinforce illness models that emphasize impaired brain connectivity.

  1. Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T

    1995-01-01

    rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP......Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed...... only in diminutive amounts in astrocytes of the neonatal rat brain, which could imply that neonatal rats are devoid of the capacity to detoxify free metals released from a brain wound. In order to examine the influence of a brain injury on the expression of metallothionein in the neonatal brain, PO...

  2. The androgen-binding protein gene is expressed in male and female rat brain.

    Science.gov (United States)

    Wang, Y M; Bayliss, D A; Millhorn, D E; Petrusz, P; Joseph, D R

    1990-12-01

    Extracellular androgen-binding proteins (ABP) are thought to modulate the regulatory functions of androgens and the trans-acting nuclear androgen receptor. Testicular ABP and plasma sex hormone-binding globulin (SHBG), which is produced in liver, are encoded by the same gene. We have now found that the ABP-SHBG gene is also expressed in male and female rat brain. Immunoreactive ABP was found to be present in neuronal cell bodies throughout the brain as well as in fibers of the hypothalamic median eminence. The highest concentrations of immunoreactive cell bodies were located in the supraoptic and paraventricular nuclei. Likewise, ABP mRNA was present in all brain regions examined. Analysis of cDNA clones representing brain ABP mRNAs revealed amino acid sequence differences in brain and testicular ABPs. The protein encoded by an alternatively processed RNA has sequence characteristics suggesting that the protein could act as a competitior of ABP binding to cell surface receptors. These data and gene-sequencing experiments indicate that a specific ABP gene promoter is used for transcription initiation in brain. ABP may function in brain as an androgen carrier protein; however, in view of the widespread presence of ABP and ABP mRNA in brain, the protein may have a much broader, yet unknown, function. PMID:1701136

  3. Cu/Zn superoxide dismutase expression in the postnatal rat brain following an excitotoxic injury

    Directory of Open Access Journals (Sweden)

    Faiz Maryam

    2005-06-01

    Full Text Available Abstract Background In the nervous system, as in other organs, Cu/Zn superoxide dismutase (Cu/Zn SOD is a key antioxidant enzyme involved in superoxide detoxification in normal cellular metabolism and after cell injury. Although it has been suggested that immature brain has a different susceptibility to oxidative damage than adult brain, the distribution and cell-specific expression of this enzyme in immature brain and after postnatal brain damage has not been documented. Methods In this study, we used immunohistochemistry and western blot to analyze the expression of Cu/Zn SOD in intact immature rat brain and in immature rat brain after an NMDA-induced excitotoxic cortical injury performed at postnatal day 9. Double immunofluorescence labelling was used to identify Cu/Zn SOD-expressing cell populations. Results In intact immature brain, Cu/Zn SOD enzyme was widely expressed at high levels in neurons mainly located in cortical layers II, III and V, in the sub-plate, in the pyriform cortex, in the hippocampus, and in the hypothalamus. Glial fibrillary acidic protein-positive cells only showed Cu/Zn SOD expression in the glia limitans and in scattered cells of the ventricle walls. No expression was detected in interfascicular oligodendroglia, microglia or endothelial cells. Following excitotoxic damage, neuronal Cu/Zn SOD was rapidly downregulated (over 2–4 hours at the injection site before neurodegeneration signals and TUNEL staining were observed. Later, from 1 day post-lesion onward, an upregulation of Cu/Zn SOD was found due to increased expression in astroglia. A further increase was observed at 3, 5 and 7 days that corresponded to extensive induction of Cu/Zn SOD in highly reactive astrocytes and in the astroglial scar. Conclusion We show here that, in the intact immature brain, the expression of Cu/Zn SOD was mainly found in neurons. When damage occurs, a strong and very rapid downregulation of this enzyme precedes neuronal degeneration

  4. Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake

    OpenAIRE

    Yoon, Ye Ran; Baik, Ja-Hyun

    2015-01-01

    Background The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. Methods We examined the expression leve...

  5. Bioactive products of arginine in sepsis: tissue and plasma composition after LPS and iNOS blockade.

    Science.gov (United States)

    Lortie, M J; Ishizuka, S; Schwartz, D; Blantz, R C

    2000-06-01

    Blockade or gene deletion of inducible nitric oxide synthase (iNOS) fails to fully abrogate all the sequelae leading to the high morbidity of septicemia. An increase in substrate uptake may be necessary for the increased production of nitric oxide (NO), but arginine is also a precursor for other bioactive products. Herein, we demonstrate an increase in alternate arginine products via arginine and ornithine decarboxylase in rats given lipopolysaccharide (LPS). The expression of iNOS mRNA in renal tissue was evident 60 but not 30 min post-LPS, yet a rapid decrease in blood pressure was obtained within 30 min that was completely inhibited by selective iNOS blockade. Plasma levels of arginine and ornithine decreased by at least 30% within 60 min of LPS administration, an effect not inhibited by the iNOS blocker L-N(6)(1-iminoethyl)lysine (L-NIL). Significant increases in plasma nitrates and citrulline occurred only 3-4 h post-LPS, an effect blocked by L-NIL pretreatment. The intracellular composition of organs harvested 6 h post-LPS reflected tissue-specific profiles of arginine and related metabolites. Tissue arginine concentration, normally an order of magnitude higher than in plasma, did not decrease after LPS. Pretreatment with L-NIL had a significant impact on the disposition of tissue arginine that was organ specific. These data demonstrate changes in arginine metabolism before and after de novo iNOS activity. Selective blockade of iNOS did not prevent uptake and can deregulate the production of other bioactive arginine metabolites. PMID:10837347

  6. Exclusive neuronal expression of SUCLA2 in the human brain

    DEFF Research Database (Denmark)

    Dobolyi, Arpád; Ostergaard, Elsebet; Bagó, Attila G;

    2015-01-01

    associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here, we show that immunoreactivity of A-SUCL-β in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a...... was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming β...... subunit (G-SUCL-β) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL-β immunoreactivity that was, however, not upregulated in samples obtained from...

  7. Expression and Localization of TRK-Fused Gene Products in the Rat Brain and Retina

    International Nuclear Information System (INIS)

    The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It has been reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. However, no information regarding the localization of Tfg in rat tissues is available. In this study, we investigated the expression of Tfg mRNA in normal rat tissues using reverse transcription-polymerase chain reaction (RT-PCR). We also produced an antibody against Tfg gene products and examined the localization of TFG in the rat brain and retina. The RT-PCR experiments demonstrated that two types of Tfg mRNA were expressed in rat tissues: the conventional form of Tfg (cTfg) and a novel variant form, retinal Tfg (rTfg). RT-PCR analyses demonstrated that cTfg was ubiquitously expressed in rat tissues, while rTfg was predominantly expressed in the brain and retina. Western blot analysis demonstrated two bands with molecular weights of about 30 kDa and 50 kDa in the rat brain. Immunohistochemistry indicated that TFG proteins were predominantly expressed by neurons in the brain. In the rat retina, intense TFG-immunoreactivity was detected in the layer of rods and cones and the outer plexiform layer

  8. Expression patterns of Neil3 during embryonic brain development and neoplasia

    Directory of Open Access Journals (Sweden)

    Bjørås Magnar

    2009-05-01

    Full Text Available Abstract Background The base excision repair pathway is responsible for repairing small DNA base lesions caused by endogenous and exogenous damaging agents. Repair is initiated by DNA glycosylases that recognize and remove the lesions. NEIL3 is one of 11 mammalian DNA glycosylases identified to date and it was discovered on the basis of sequence homology to the E. coli Fpg and Nei glycosylases. Difficulties in purifying the protein have limited its biochemical characterization and in contrast to the other glycosylases, its function remains unclear. Results In this study we describe the expression pattern of Neil3 during mouse embryonic development with special focus on brain development. We have also looked at the expression of NEIL3 in several normal and tumor tissues. Quantitative real-time PCR and in situ hybridization revealed that Neil3 was highly expressed at embryonic days 12–13, when neurogenesis starts. The expression decreased during development and in the adult brain,Neil3 could not be detected in any of the brain areas examined by quantitative real-time PCR. During embryogenesis and in newborn mice specific expression was observed in areas known to harbour neural stem and progenitor cells such as the subventricular zone and the dentate gyrus. Finally, NEIL3 expression was higher in tumors compared to normal tissues, except for testis and pancreas. Conclusion Our findings indicate that mammalian NEIL3 is specifically expressed in brain areas where neurogenesis takes place during development and that its expression is tightly regulated both temporally and spatially. In addition, NEIL3 seems to be upregulated in tumor tissues compared to normal tissues. Altogether, mammalian NEIL3 seems to be highly expressed in cells with high proliferative potential.

  9. A novel suicide gene therapy using iNOS

    International Nuclear Information System (INIS)

    The role of NO in tumours is extremely complex; depending on the concentration it has major effects on vascular tone, endothelial proliferation, cell viability and radiosensitivity. As such, it is not surprising that its manipulation has been identified by many investigators as an exciting target for cancer therapy. The use of a gene therapy strategy utilising the iNOS gene to produce NO offers the potential for targeting NO production specifically within the tumour volume, combined with high NO-generating capacity. We have shown that iNOS gene therapy driven by a strong constitutive promoter (CMV) results in significant growth delay of the murine RIF-1 tumour in vivo. Due to the potent nature of NO any gene therapy strategy will require at lest one level of specificity. We have used the X-ray inducible WAF1/iNOS construct to confine NO generation to within the radiation field i.e. the tumour. A single injection of the X-ray inducible WAF1/iNOS construct followed, 16 h later, by an induction dose of 4 Gy X-rays resulted in significant enhancement of the cell killing effect of subsequent therapeutic doses of X-rays in the same tumour model. The effect was equivalent to a sensitiser enhancement ratio of ∼2.0, half the radiation dose being required to produce the biological effect when iNOS gene therapy was combined with radiation. Intra-tumoural injection of the WAF1/iNOS construct followed by 4 Gy X-rays also resulted in significant radiosensitisation in the HT29 xenograft model. We have so far demonstrated the cytotoxic and radiosensitising potential of iNOS gene therapy, however there are further benefits to the use of NO as an anti-cancer agent. These include anti-angiogenic effects and inhibition of tumour metastasis. Further studies will enable the design of a clinically appropriate protocol to be established

  10. Early expression of hypocretin/orexin in the chick embryo brain.

    Directory of Open Access Journals (Sweden)

    Kyle E Godden

    Full Text Available Hypocretin/Orexin (H/O neuropeptides are released by a discrete group of neurons in the vertebrate hypothalamus which play a pivotal role in the maintenance of waking behavior and brain state control. Previous studies have indicated that the H/O neuronal development differs between mammals and fish; H/O peptide-expressing cells are detectable during the earliest stages of brain morphogenesis in fish, but only towards the end of brain morphogenesis (by ∼ 85% of embryonic development in rats. The developmental emergence of H/O neurons has never been previously described in birds. With the goal of determining whether the chick developmental pattern was more similar to that of mammals or of fish, we investigated the emergence of H/O-expressing cells in the brain of chick embryos of different ages using immunohistochemistry. Post-natal chick brains were included in order to compare the spatial distribution of H/O cells with that of other vertebrates. We found that H/O-expressing cells appear to originate from two separate places in the region of the diencephalic proliferative zone. These developing cells express the H/O neuropeptide at a comparatively early age relative to rodents (already visible at 14% of the way through fetal development, thus bearing a closer resemblance to fish. The H/O-expressing cell population proliferates to a large number of cells by a relatively early embryonic age. As previously suggested, the distribution of H/O neurons is intermediate between that of mammalian and non-mammalian vertebrates. This work suggests that, in addition to its roles in developed brains, the H/O peptide may play an important role in the early embryonic development of non-mammalian vertebrates.

  11. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Milsted, A.; Barna, B.P.; Ransohoff, R.M.; Brosnihan, K.B.; Ferrario, C.M. (Cleveland Clinic Foundation, OH (USA))

    1990-08-01

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures.

  12. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    International Nuclear Information System (INIS)

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures

  13. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

    Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  14. A comparison of brain gene expression levels in domesticated and wild animals.

    Directory of Open Access Journals (Sweden)

    Frank W Albert

    2012-09-01

    Full Text Available Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits. We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30-75 genes (less than 1% of expressed genes were differentially expressed, while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.

  15. Pattern of CXCR7 Gene Expression in Mouse Brain Under Normal and Inflammatory Conditions.

    Science.gov (United States)

    Banisadr, Ghazal; Podojil, Joseph R; Miller, Stephen D; Miller, Richard J

    2016-03-01

    The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 acting via its G-protein coupled receptor (GPCR) CXCR4 has been implicated in neurogenesis, neuromodulation, brain inflammation, HIV-1 encephalopathy and tumor growth. CXCR7 was identified as an alternate receptor for SDF-1/CXCL12. Characterization of CXCR7-deficient mice demonstrated a role for CXCR7 in fetal endothelial biology, cardiac development, and B-cell localization. Despite its ligand binding properties, CXCR7 does not seem to signal like a conventional GPCR. It has been suggested that CXCR7 may not function alone but in combination with CXCR4. Here, we investigated the regional localization of CXCR7 receptors in adult mouse brain using CXCR7-EGFP transgenic mice. We found that the receptors were expressed in various brain regions including olfactory bulb, cerebral cortex, hippocampus, subventricular zone (SVZ), hypothalamus and cerebellum. Extensive CXCR7 expression was associated with cerebral blood vessels. Using cell type specific markers, CXCR7 expression was found in neurons, astrocytes and oligodendrocyte progenitors. GAD-expressing neurons exhibited CXCR7 expression in the hippocampus. Expression of CXCR7 in the dentate gyrus included cells that expressed nestin, GFAP and cells that appeared to be immature granule cells. In mice with Experimental Autoimmune Encephalomyelitis (EAE), CXCR7 was expressed by migrating oligodendrocyte progenitors in the SVZ. We then compared the distribution of SDF-1/CXCL12 and CXCR7 using bitransgenic mice expressing both CXCR7-EGFP and SDF-1-mRFP. Enhanced expression of SDF-1/CXCL12 and CXCR7 was observed in the corpus callosum, SVZ and cerebellum. Overall, the expression of CXCR7 in normal and pathological nervous system suggests CXCR4-independent functions of SDF-1/CXCL12 mediated through its interaction with CXCR7. PMID:25997895

  16. Identification of a set of genes showing regionally enriched expression in the mouse brain

    Directory of Open Access Journals (Sweden)

    Marra Marco A

    2008-07-01

    Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

  17. Housekeeping while brain's storming Validation of normalizing factors for gene expression studies in a murine model of traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Escriou Virginie

    2008-07-01

    Full Text Available Abstract Background Traumatic brain injury models are widely studied, especially through gene expression, either to further understand implied biological mechanisms or to assess the efficiency of potential therapies. A large number of biological pathways are affected in brain trauma models, whose elucidation might greatly benefit from transcriptomic studies. However the suitability of reference genes needed for quantitative RT-PCR experiments is missing for these models. Results We have compared five potential reference genes as well as total cDNA level monitored using Oligreen reagent in order to determine the best normalizing factors for quantitative RT-PCR expression studies in the early phase (0–48 h post-trauma (PT of a murine model of diffuse brain injury. The levels of 18S rRNA, and of transcripts of β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH, β-microtubulin and S100β were determined in the injured brain region of traumatized mice sacrificed at 30 min, 3 h, 6 h, 12 h, 24 h and 48 h post-trauma. The stability of the reference genes candidates and of total cDNA was evaluated by three different methods, leading to the following rankings as normalization factors, from the most suitable to the less: by using geNorm VBA applet, we obtained the following sequence: cDNA(Oligreen; GAPDH > 18S rRNA > S100β > β-microtubulin > β-actin; by using NormFinder Excel Spreadsheet, we obtained the following sequence: GAPDH > cDNA(Oligreen > S100β > 18S rRNA > β-actin > β-microtubulin; by using a Confidence-Interval calculation, we obtained the following sequence: cDNA(Oligreen > 18S rRNA; GAPDH > S100β > β-microtubulin > β-actin. Conclusion This work suggests that Oligreen cDNA measurements, 18S rRNA and GAPDH or a combination of them may be used to efficiently normalize qRT-PCR gene expression in mouse brain trauma injury, and that β-actin and β-microtubulin should be avoided. The potential of total cDNA as measured by Oligreen as a

  18. A common gene expression signature in Huntington’s disease patient brain regions

    OpenAIRE

    Neueder, Andreas; Bates, Gillian P.

    2014-01-01

    Background Gene expression data provide invaluable insights into disease mechanisms. In Huntington’s disease (HD), a neurodegenerative disease caused by a tri-nucleotide repeat expansion in the huntingtin gene, extensive transcriptional dysregulation has been reported. Conventional dysregulation analysis has shown that e.g. in the caudate nucleus of the post mortem HD brain the gene expression level of about a third of all genes was altered. Owing to this large number of dysregulated genes, t...

  19. Inflammation induces neuro-lymphatic protein expression in multiple sclerosis brain neurovasculature

    OpenAIRE

    Chaitanya, Ganta Vijay; Omura, Seiichi; Sato, Fumitaka; Martinez, Nicholas E.; Minagar, Alireza; Ramanathan, Murali; Guttman, Bianca Weinstock; Zivadinov, Robert; Tsunoda, Ikuo; Alexander, Jonathan S

    2013-01-01

    Background Multiple sclerosis (MS) is associated with ectopic lymphoid follicle formation. Podoplanin+ (lymphatic marker) T helper17 (Th17) cells and B cell aggregates have been implicated in the formation of tertiary lymphoid organs (TLOs) in MS and experimental autoimmune encephalitis (EAE). Since podoplanin expressed by Th17 cells in MS brains is also expressed by lymphatic endothelium, we investigated whether the pathophysiology of MS involves inductions of lymphatic proteins in the infla...

  20. Identification of Wnt Genes Expressed in Neural Progenitor Zones during Zebrafish Brain Development

    OpenAIRE

    Robert N Duncan; Panahi, Samin; Piotrowski, Tatjana; Dorsky, Richard I.

    2015-01-01

    Wnt signaling regulates multiple aspects of vertebrate central nervous system (CNS) development, including neurogenesis. However, vertebrate genomes can contain up to 25 Wnt genes, the functions of which are poorly characterized partly due to redundancy in their expression. To identify candidate Wnt genes as candidate mediators of pathway activity in specific brain progenitor zones, we have performed a comprehensive expression analysis at three different stages during zebrafish development. A...

  1. A cross-laboratory comparison of expression profiling data from normal human postmortem brain

    OpenAIRE

    Mistry, Meeta; Pavlidis, Paul

    2010-01-01

    Expression profiling of post-mortem human brain tissue has been widely used to study molecular changes associated with neuropsychiatric diseases as well as normal processes such as aging. Changes in expression associated with factors such as age, gender or postmortem interval are often more pronounced than changes associated with disease. Therefore in addition to being of interest in their own right, careful consideration of these effects are important in the interpretation of disease studies...

  2. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

  3. iNOS ablation does not improve specific force of the extensor digitorum longus muscle in dystrophin-deficient mdx4cv mice.

    Directory of Open Access Journals (Sweden)

    Dejia Li

    Full Text Available Nitrosative stress compromises force generation in Duchenne muscular dystrophy (DMD. Both inducible nitric oxide synthase (iNOS and delocalized neuronal NOS (nNOS have been implicated. We recently demonstrated that genetic elimination of nNOS significantly enhanced specific muscle forces of the extensor digitorum longus (EDL muscle of dystrophin-null mdx4cv mice (Li D et al J. Path. 223:88-98, 2011. To determine the contribution of iNOS, we generated iNOS deficient mdx4cv mice. Genetic elimination of iNOS did not alter muscle histopathology. Further, the EDL muscle of iNOS/dystrophin DKO mice yielded specific twitch and tetanic forces similar to those of mdx4cv mice. Additional studies suggest iNOS ablation did not augment nNOS expression neither did it result in appreciable change of nitrosative stress markers in muscle. Our results suggest that iNOS may play a minor role in mediating nitrosative stress-associated force reduction in DMD.

  4. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Godbole, Madan M., E-mail: madangodbole@yahoo.co.in [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India)

    2010-07-02

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  5. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    International Nuclear Information System (INIS)

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1α, NRF-1α and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  6. Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development

    DEFF Research Database (Denmark)

    Venø, Morten T; Hansen, Thomas B; Venø, Susanne T;

    2015-01-01

    BACKGROUND: Recently, thousands of circular RNAs (circRNAs) have been discovered in various tissues and cell types from human, mouse, fruit fly and nematodes. However, expression of circRNAs across mammalian brain development has never been examined. RESULTS: Here we profile the expression of cir......RNA in five brain tissues at up to six time-points during fetal porcine development, constituting the first report of circRNA in the brain development of a large animal. An unbiased analysis reveals a highly complex regulation pattern of thousands of circular RNAs, with a distinct spatio...... are longer than average and more frequently contain proximal complementary SINEs, which potentially can facilitate base pairing between the flanking introns. Finally, we report the first use of RNase R treatment in combination with in situ hybridization to show dynamic subcellular localization of circ...

  7. Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of AQP4 expression in rabbits.

    Science.gov (United States)

    Chen, Jun-Hui; Yang, Li-Kun; Chen, Lei; Wang, Yu-Hai; Wu, Yun; Jiang, Bing-Jie; Zhu, Jie; Li, Pei-Pei

    2016-04-01

    The therapeutic effects of atorvastatin on early brain injury (EBI), cerebral edema and its association with aquaporin 4 (AQP4) were studied in rabbits after subarachnoid hemorrhage (SAH) using western blot analysis and the dry-wet method. Seventy-two healthy male New Zealand rabbits weighing between 2.5 and 3.2 kg were randomly divided into three groups: the SAH group (n=24), sham-operated group (n=24) and the SAH + atorvastatin group (n=24). A double SAH model was employed. The sham-operated group were injected with the same dose of saline solution, the SAH + atorvastatin group received atorvastatin 20 mg/kg/day after SAH. All rabbit brain samples were taken at 72 h after the SAH model was established successfully. Brain edema was detected using the dry-wet method after experimental SAH was induced; AQP4 and caspase-3 expression was measured by western blot analysis, and neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining at 72 h after SAH. The results indicated that brain edema and injury appeared soon after SAH, while brain edema and EBI were ameliorated and increased behavior scores were noted after prophylactic use of atorvastatin. Compared with the SAH group, the level of AQP4 and the cerebral content of water was significantly decreased (Patorvastatin, and TUNEL staining and studying the expression of caspase-3 showed that the apoptosis of neurons was reduced markedly both in the hippocampus and brain cortex by atorvastatin. The results suggest that atorvastatin ameliorated brain edema and EBI after SAH, which was related to its inhibition of AQP4 expression. Our findings provide evidence that atorvastatin is an effective and well-tolerated approach for treating SAH in various clinical settings. PMID:26935263

  8. Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX1

    Science.gov (United States)

    Ruan, Hangjun; Wang, Jingli; Hu, Lily; Lin, Ching-Shwun; Lamborn, Kathleen R; Deen, Dennis F

    1999-01-01

    Abstract The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE), which can be activated through hypoxia-inducible factor-1 (HIF-1). We transfected plasmids containing multiple copies of HRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HRE copy number, and the degree of hypoxia. PMID:10933058

  9. Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX

    Directory of Open Access Journals (Sweden)

    Hangjun Ruan

    1999-11-01

    Full Text Available The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE, which can be activated through hypoxia-inducible factor-1 (HIF-1. We transfected plasmids containing multiple copies of HIRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HIRE copy number, and the degree of hypoxia.

  10. AQP4 expression and its relationship with brain edema after gamma kife radiosurgery in rats

    International Nuclear Information System (INIS)

    Objective: To explore AQP4 expression and its relationship with brain edema after gamma knife radiosurgery (GKRS) in rats. Methods: Wistar rats were divided into two groups-the control group and experimental group. The experimental group model was established by radiating rat left rotral caudate nucleus with GKRS (100 Gy, 4 mm), and was examinded at interval times of 1 d, 3 d, 7 d, 15 d, 30 d and 45 d. Brain water content (BWC) was determined by wet-dry weighing method. AQP4 expression on mRNA and protein were measured by immunohistochemistry (ICH) and in situ hybridization (ISH). Results: In control group, AQP4 protein and its mRNA were expressed in subpial astrocytes, choroid plexus, ependyma and perivascular astrocytes. After GKRS, AQP4 protein and its mRNA in these sites were enhanced, and became most remarkable at 30 d. The positive corrlationship was showed between AQP4 and its mRNA, and AQP4 and BWC. Conclusions: AQP4 protein and its mRNA can be induced in some brain zone after irradiating rat left rotral caudate nucleus with GKRS. The increased expression of AQP4 and its mRNA may play a role in the ocurrence or development of brain edema after GKRS. (authors)

  11. Effect of permanent middle cerebral artery occlusion on Cytoglobin expression in the mouse brain

    DEFF Research Database (Denmark)

    Raida, Zindy; Reimets, Riin; Hay-Schmidt, Anders;

    2012-01-01

    Cytoglobin, a new member of the mammalian heme-globin family has been shown to bind oxygen and to have cell protective properties in vitro. Cytoglobin is specifically expressed in a subpopulation of brain neurons. Based on hypoxia-induced up regulation and proposed scavenging of reactive oxygen...

  12. Gene × Smoking Interactions on Human Brain Gene Expression: Finding Common Mechanisms in Adolescents and Adults

    Science.gov (United States)

    Wolock, Samuel L.; Yates, Andrew; Petrill, Stephen A.; Bohland, Jason W.; Blair, Clancy; Li, Ning; Machiraju, Raghu; Huang, Kun; Bartlett, Christopher W.

    2013-01-01

    Background: Numerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets…

  13. Expressive Electronic Journal Writing: Freedom of Communication for Survivors of Acquired Brain Injury

    Science.gov (United States)

    Fraas, Michael; Balz, Magdalen A.

    2008-01-01

    In addition to the impaired ability to effectively communicate, adults with acquired brain injury (ABI) also experience high incidences of depression, social isolation, and decreased quality of life. Expressive writing programs have been shown to be effective in alleviating these concomitant impairments in other populations including incarcerated…

  14. Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain

    DEFF Research Database (Denmark)

    Larsen, Karen B; Lutterodt, Melissa C; Møllgård, Kjeld;

    2010-01-01

    In rodents, the Otx2 gene is expressed in the diencephalon, mesencephalon, and cerebellum and is crucial for the development of these brain regions. Together with Otx1, Otx2 is known to cooperate with other genes to develop the caudal forebrain and, further, Otx1 is also involved in differentiation...

  15. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  16. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  17. Memory consolidation and amnesia modify 5-HT6 receptors expression in rat brain: an autoradiographic study.

    Science.gov (United States)

    Meneses, A; Manuel-Apolinar, L; Castillo, C; Castillo, E

    2007-03-12

    Traditionally, the search for memory circuits has been centered on examinations of amnesic and AD patients, cerebral lesions and, neuroimaging. A complementary alternative might be the use of autoradiography with radioligands. Indeed, ex vivo autoradiographic studies offer the advantage to detect functionally active receptors altered by pharmacological tools and memory formation. Hence, herein the 5-HT(6) receptor antagonist SB-399885 and the amnesic drugs scopolamine or dizocilpine were used to manipulate memory consolidation and 5-HT(6) receptors expression was determined by using [(3)H]-SB-258585. Thus, memory consolidation was impaired in scopolamine and dizocilpine treated groups relative to control vehicle but improved it in SB-399885-treated animals. SB-399885 improved memory consolidation seems to be associated with decreased 5-HT(6) receptors expression in 15 out 17 brain areas. Scopolamine or dizocilpine decreased 5-HT(6) receptors expression in nine different brain areas and increased it in CA3 hippocampus or other eight areas, respectively. In brain areas thought to be in charge of procedural memory such basal ganglia (i.e., nucleus accumbens, caudate putamen, and fundus striate) data showed that relative to control animals amnesic groups showed diminished (scopolamine) or augmented (dizocilpine) 5-HT(6) receptor expression. SB-399885 showing improved memory displayed an intermediate expression in these same brain regions. A similar intermediate expression occurs with regard to amygdala, septum, and some cortical areas in charge of explicit memory storage. However, relative to control group amnesic and SB-399885 rats in the hippocampus, region where explicit memory is formed, showed a complex 5-HT(6) receptors expression. In conclusion, these results indicate neural circuits underlying the effects of 5-HT(6) receptor antagonists in autoshaping task and offer some general clues about cognitive processes in general. PMID:17267053

  18. Gene expression patterns in primary neuronal clusters of the Drosophila embryonic brain

    Science.gov (United States)

    Sprecher, Simon G.; Reichert, Heinrich; Hartenstein, Volker

    2014-01-01

    The brain of Drosophila is formed by approximately 100 lineages, each lineage being derived from a stem cell-like neuroblast that segregates from the procephalic neurectoderm of the early embryo. A neuroblast map has been established in great detail for the early embryo, and a suite of molecular markers has been defined for all neuroblasts included in this map (Urbach and Technau, 2003a). However, the expression of these markers was not followed into later embryonic or larval stages, mainly due to the fact that anatomical landmarks to which expression patterns could be related had not been defined. Such markers, in the form of stereotyped clusters of neurons whose axons project along cohesive bundles (“primary axon bundles” or “PABs”) are now available (Younossi-Hartenstein et al., 2006). In the present study we have mapped the expression of molecular markers in relationship to primary neuronal clusters and their PABs. The markers we analyzed include many of the genes involved in patterning of the brain along the anteroposterior axis (cephalic gap genes, segment polarity genes) and dorso-ventral axis (columnar patterning genes), as well as genes expressed in the dorsal protocerebrum and visual system (early eye genes). Our analysis represents an important step along the way to identify neuronal lineages of the mature brain with genes expressed in the early embryo in discrete neuroblasts. Furthermore, the analysis helped us to reconstruct the morphogenetic movements that transform the two-dimensional neuroblast layer of the early embryo into the three-dimensional larval brain and provides the basis for deeper understanding of how the embryonic brain develops. PMID:17300994

  19. Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Zhen-Guo Cheng; Guo-Dong Zhang; Peng-Qiang Shi; Bao-Shun Du

    2013-01-01

    Objective: To explore the expression of Nrf2/ARE pathway in hindbrain tissue after the traumatic brain injury (TBI) and its anti-oxidative stress effect in the secondary nerve injury. Methods:The mice with Nrf2 gene knockout were used for the establishment of brain injury model. The experimental animals were divided into four groups: (Nrf2+/+) sham-operation group, (Nrf2+/+) brain injury group, (Nrf2-/-) sham-operation group and (Nrf2-/-) brain injury group. The specimen 24 h after cerebral trauma was selected. Then RT-PCR method was adopted to detect the expression of Nrf2 mRNA in brain; Western blotting method was adopted to detect the levels of Nrf2, HO-1 and NQO1 proteins in brain; ELISA method was adopted to detect the oxidative stress indicators:protein carbonyls, 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2’-deoxyguanosine (8-OHdG). Results: The Nrf2 mRNA and protein of Nrf2-/- mice were not expressed, and the difference of the relative amount of Nrf2 mRNA between Nrf2+/+ TBI group and Nrf2+/+ sham-operation group was not statistically significant (P>0.05); the level of Nrf2 protein in Nrf2+/+ TBI group increased significantly compared with the Nrf2+/+ sham-operation group (P0.05); there was only a little amount of expression of protein carbonyls, 4-HNE and 8-OHdG proteins in brain tissues in the Nrf2+/+ and Nrf2-/- sham-operation groups, and the difference was not statistically significant (P>0.05); after brain injury, the three oxidative stress indicators were significantly up-regulated in the Nrf2+/+ and Nrf2-/-groups, and the up-regulation of the latter group was more significant (P<0.01). Conclusions:After TBI the Nrf2/ARE pathway is activated and the activity of Nrf2 transcription regulation increases. However, the regulation dose not occur in the gene transcription level and only could increase the Nrf2 protein level, while the mRNA expression level has no obvious change. The nerve cell protective effect of Nrf2/ARE pathway in TBI achieves through

  20. RPC detector characteristics and performance for INO-ICAL experiment

    Science.gov (United States)

    Kumar, A.; Gaur, A.; Hasbuddin, Md.; Naimuddin, Md.

    2016-03-01

    The India-based Neutrino Observatory (INO) is an approved multi-institutional collaboration neutrino physics project, aimed at building an underground laboratory in the southern India. INO will utilize a large magnetized Iron Calorimeter (ICAL) detector to study the atmospheric neutrinos, and to explore the unresolved issues related to neutrinos. The Resistive Plate Chambers (RPCs), interleaved in between iron absorber layers, are going to be used as the active signal readouts for the ICAL experiment at INO. The research and development is carried out to find structural quality and electrical response for RPC electrode materials available within local domain. The assembled 2 mm gap RPCs are tested using cosmic muons for their detection performance. The study also incorporates preliminary results on detector timing and signal induced charge measurements.

  1. Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression

    Directory of Open Access Journals (Sweden)

    Heinrich Gerhard

    2004-05-01

    Full Text Available Abstract Background Precise control of developmental and cell-specific expression of the brain-derived neurotrophic factor (BDNF gene is essential for normal neuronal development and the diverse functions of BDNF in the adult organism. We previously showed that the zebrafish BDNF gene has multiple promoters. The complexity of the promoter structure and the mechanisms that mediate developmental and cell-specific expression are still incompletely understood. Results Comparison of pufferfish and zebrafish BDNF gene sequences as well as 5' RACE revealed three additional 5' exons and associated promoters. RT-PCR with exon-specific primers showed differential developmental and organ-specific expression. Two exons were detected in the embryo before transcription starts. Of the adult organs examined, the heart expressed a single 5' exon whereas the brain, liver and eyes expressed four of the seven 5' exons. Three of the seven 5' exons were not detectable by RT-PCR. Injection of promoter/GFP constructs into embryos revealed distinct expression patterns. The 3' flank profoundly affected expression in a position-dependent manner and a highly conserved sequence (HCS1 present in 5' exon 1c in a dehancer-like manner. Conclusions The zebrafish BDNF gene is as complex in its promoter structure and patterns of differential promoter expression as is its murine counterpart. The expression of two of the promoters appears to be regulated in a temporally and/or spatially highly circumscribed fashion. The 3' flank has a position-dependent effect on expression, either by affecting transcription termination or post-transcriptional steps. HCS1, a highly conserved sequence in 5' exon 1c, restricts expression to primary sensory neurons. The tools are now available for detailed genetic and molecular analyses of zebrafish BDNF gene expression.

  2. Cholestasis induced antinociception and decreased gene expression of MOR1 in rat brain.

    Science.gov (United States)

    Ahmadi, S; Karami, Z; Mohammadian, A; Khosrobakhsh, F; Rostamzadeh, J

    2015-01-22

    We examined antinociception and gene expression of mu-opioid receptor 1 (MOR1) in some brain areas of cholestatic rats, 21 days after common bile duct ligation (BDL). Cholestasis was induced in male Wistar rats during laparotomy and common BDL. Pain behavior was assessed on days 7, 14 or 21 of BDL using a hotplate test in control, sham and cholestatic groups. On day 21 of BDL, other groups of rats were sacrificed, whole brains were extracted, and the hypothalamus, prefrontal cortex (PFC), hippocampus and striatum in control, sham and cholestatic rats were dissected. We used a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for evaluating MOR1 gene expression. The results revealed that cholestatic rats showed significant antinociception on days 14 and 21 of ligation with the most significant effect on day 21, which was prevented by naloxone (1 mg/kg). On the other hand, the expression of MOR1 gene compared to the sham group was decreased by 42% in the hypothalamus, 41% in the PFC, and 67% in the hippocampus after 21 days of BDL, while no significant change in its expression in the striatum was observed. It can be concluded that a change in endogenous opioid levels and its subsequent influence on the gene expression of MOR in some areas of the rat brain may underlie the altered nociception and other possible pathological changes such as pruritus after induction of cholestasis. PMID:25290008

  3. Expression of activity-dependent neuroprotective protein in the brain of adult rats.

    Science.gov (United States)

    Gennet, N; Herden, C; Bubb, V J; Quinn, J P; Kipar, A

    2008-03-01

    Activity-dependent neuroprotective protein (ADNP) is a VIP-regulated gene, which is essential for brain development. A synthetic peptide (NAP) derived from the ADNP sequence is highly neuroprotective, therefore it has been hypothesised that ADNP has a similar role. ADNP contains classical transcription factor motifs and nuclear localisation domains, but it has also been reported to be secreted and to co-localise with microtubules, indicating that ADNP may have multiple functions. We investigated the pattern of ADNP expression by immunohistology in normal rat brain, in order to generate a framework for future studies examining changes in ADNP expression in response to noxious stimuli or in models of disease. We found widespread ADNP-like immunoreactivity in neurons throughout the rat brain, with the highest expression in the cerebellum, and strong expression in the thalamus, mesencephalon, pons and medulla oblongata. ADNP-like immunoreactivity was mainly observed in the cytoplasm of neurons, and fibre tracts were often strongly positive as well. In addition, positive neuronal nuclei were occasionally observed. ADNP-like immunoreactivity was lost in degenerating "dark" neurons, whereas it appeared to locate to the nucleus in some of the morphologically unaltered adjacent cells. Occasional astrocyte and microglial cells were also positive. We suggest that the widespread expression of ADNP may correlate with the wide-ranging protective effects of NAP, and that the cytoplasmic and axonal localisation of ADNP-like immunoreactivity suggests additional, non-transcriptional functions of ADNP. PMID:18072088

  4. Evolutionary expression of the neuronal form of the src protein in the brain.

    OpenAIRE

    Yang, X. M.; Martinez, R; J. Le Beau; Wiestler, O; Walter, G

    1989-01-01

    The protooncogene src encodes two proteins, designated pp60c-src+ and pp60c-src.pp60c-src+ is expressed only in neurons, whereas pp60c-src is expressed in neuronal and nonneuronal cells. pp60c-src+ differs from pp60c-src in that it contains an insert of 6 amino acids. To study the evolutionary conservation of the 6-amino acid insert, the expression of pp60c-src+ in the brain of animals from different classes was assayed by using pp60c-src+-specific antibodies raised against a synthetic peptid...

  5. Novel MicroRNAs Differentially Expressed during Aging in the Mouse Brain

    OpenAIRE

    Inukai, Sachi; de Lencastre, Alexandre; Turner, Michael; Slack, Frank

    2012-01-01

    MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 558 known miRNAs and identification of...

  6. Gene co-expression networks shed light into diseases of brain iron accumulation

    Science.gov (United States)

    Bettencourt, Conceição; Forabosco, Paola; Wiethoff, Sarah; Heidari, Moones; Johnstone, Daniel M.; Botía, Juan A.; Collingwood, Joanna F.; Hardy, John; Milward, Elizabeth A.; Ryten, Mina; Houlden, Henry

    2016-01-01

    Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach. We used whole-transcriptome gene expression data from human brain samples originating from 101 neuropathologically normal individuals (10 brain regions) to generate weighted gene co-expression networks and cluster the 10 known NBIA genes in an unsupervised manner. We investigated NBIA-enriched networks for relevant cell types and pathways, and whether they are disrupted by iron loading in NBIA diseased tissue and in an in vivo mouse model. We identified two basal ganglia gene co-expression modules significantly enriched for NBIA genes, which resemble neuronal and oligodendrocytic signatures. These NBIA gene networks are enriched for iron-related genes, and implicate synapse and lipid metabolism related pathways. Our data also indicates that these networks are disrupted by excessive brain iron loading. We identified multiple cell types in the origin of NBIA disorders. We also found unforeseen links between NBIA networks and iron-related processes, and demonstrate convergent pathways connecting NBIAs and phenotypically overlapping diseases. Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention. PMID:26707700

  7. Merilni modul za višino kvadrokopterja nad tlemi

    OpenAIRE

    Klajderič, Aljoša

    2016-01-01

    Tematika diplomske naloge je opis in izdelava višinomera za kvadrokopterje. Višinomer je instrument, ki meri višino objekta nad ravnjo nadmorske višine. Za merjenje višine se uporabljajo metode, ki temeljijo na preletu ultrazvočnega valovanja ter na razliki zračnega tlaka. Merilniški modul meri višino na obeh fizikalnih načelih, torej na preletu ultrazvočnega valovanja, tlačni razliki in na fuzijski ravni oziroma na združitvi obeh fizikalnih načel. Namen diplomske naloge je bilo razumeti omej...

  8. Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

    Science.gov (United States)

    Ramesh, Govindarajan; Wu, Honglu

    Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

  9. Effect of Hemin on Brain Alterations and Neuroglobin Expression in Water Immersion Restraint Stressed Rats

    Directory of Open Access Journals (Sweden)

    Merhan Ragy

    2016-01-01

    Full Text Available In the brain, the heme oxygenase (HO system has been reported to be very active and its modulation seems to play a crucial role in the pathophysiology of neurodegenerative disorders. Hemin as HO-1 inducer has been shown to attenuate neuronal injury so the goal of this study was to assess the effect of hemin therapy on the acute stress and how it would modulate neurological outcome. Thirty male albino rats were divided into three groups: control group and stressed group with six-hour water immersion restraint stress (WIRS and stressed group, treated with hemin, in which each rat received a single intraperitoneal injection of hemin at a dose level of 50 mg/kg body weight at 12 hours before exposure to WIRS. Stress hormones, oxidative stress markers, malondialdehyde (MDA, and total antioxidant capacity (TAC were measured and expressions of neuroglobin and S100B mRNA in brain tissue were assayed. Our results revealed that hemin significantly affects brain alterations induced by acute stress and this may be through increased expression of neuroglobin and through antioxidant effect. Hemin decreased blood-brain barrier damage as it significantly decreased the expression of S100B. These results suggest that hemin may be an effective therapy for being neuroprotective against acute stress.

  10. Expression of hippocampal brain-derived neurotrophic factor and its receptors in Stanley consortium brains

    OpenAIRE

    Dunham, Jason S.; Deakin, J. F. William; Miyajima, Fabio; Payton, Tony; Toro, Carla Tatiana

    2009-01-01

    Several lines of evidence implicate BDNF in the pathophysiology of psychiatric illness. BDNF polymorphisms have also been associated with the risk of schizophrenia and mood disorders. We therefore investigated whether levels of (pro)BDNF and receptor proteins, TrkB and p75, are altered in hippocampus in schizophrenia and mood disorder and whether polymorphisms in each gene influenced protein expression. Formalin-fixed paraffin-embedded hippocampal sections from subjects with...

  11. Orbitrap mass spectrometry characterization of hybrid chondroitin/dermatan sulfate hexasaccharide domains expressed in brain.

    Science.gov (United States)

    Robu, Adrian C; Popescu, Laurentiu; Munteanu, Cristian V A; Seidler, Daniela G; Zamfir, Alina D

    2015-09-15

    In the central nervous system, chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) modulate neurotrophic effects and glial cell maturation during brain development. Previous reports revealed that GAG composition could be responsible for CS/DS activities in brain. In this work, for the structural characterization of DS- and CS-rich domains in hybrid GAG chains extracted from neural tissue, we have developed an advanced approach based on high-resolution mass spectrometry (MS) using nanoelectrospray ionization Orbitrap in the negative ion mode. Our high-resolution MS and multistage MS approach was developed and applied to hexasaccharides obtained from 4- and 14-week-old mouse brains by GAG digestion with chondroitin B and in parallel with AC I lyase. The expression of DS- and CS-rich domains in the two tissues was assessed comparatively. The analyses indicated an age-related structural variability of the CS/DS motifs. The older brain was found to contain more structures and a higher sulfation of DS-rich regions, whereas the younger brain was found to be characterized by a higher sulfation of CS-rich regions. By multistage MS using collision-induced dissociation, we also demonstrated the incidence in mouse brain of an atypical [4,5-Δ-GlcAGalNAc(IdoAGalNAc)2], presenting a bisulfated CS disaccharide formed by 3-O-sulfate-4,5-Δ-GlcA and 6-O-sulfate-GalNAc moieties. PMID:26123275

  12. Effects of Flight on Gene Expression and Aging in the Honey Bee Brain and Flight Muscle

    Directory of Open Access Journals (Sweden)

    Michelle M. Elekonich

    2012-12-01

    Full Text Available Honey bees move through a series of in-hive tasks (e.g., “nursing” to outside tasks (e.g., “foraging” that are coincident with physiological changes and higher levels of metabolic activity. Social context can cause worker bees to speed up or slow down this process, and foragers may revert back to their earlier in-hive tasks accompanied by reversion to earlier physiological states. To investigate the effects of flight, behavioral state and age on gene expression, we used whole-genome microarrays and real-time PCR. Brain tissue and flight muscle exhibited different patterns of expression during behavioral transitions, with expression patterns in the brain reflecting both age and behavior, and expression patterns in flight muscle being primarily determined by age. Our data suggest that the transition from behaviors requiring little to no flight (nursing to those requiring prolonged flight bouts (foraging, rather than the amount of previous flight per se, has a major effect on gene expression. Following behavioral reversion there was a partial reversion in gene expression but some aspects of forager expression patterns, such as those for genes involved in immune function, remained. Combined with our real-time PCR data, these data suggest an epigenetic control and energy balance role in honey bee functional senescence.

  13. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  14. Influence of differential expression of acetylcholinesterase in brain and muscle on respiration

    OpenAIRE

    Boudinot, Eliane; Bernard, Véronique; Camp, Shelley; Taylor, Palmer; Champagnat, Jean; Krejci, Eric; Foutz, Arthur S.

    2008-01-01

    A mouse strain with a deleted acetylcholinesterase (AChE) gene (AChE knockout) shows a decreased inspiration time and increased tidal volume and ventilation. To investigate the respective roles of AChE in brain and muscle, we recorded respiration by means of whole-body plethysmography in knockout mice with tissue selective deletions in AChE expression. A mouse strain with the anchoring domains of AChE deleted (del E5+6 knockout mice) has very low activity in the brain and neuromuscular juncti...

  15. Common Patterns of Bcl-2 Family Gene Expression in Two Traumatic Brain Injury Models

    OpenAIRE

    Strauss, Kenneth I.; NARAYAN, RAJ K.; Raghupathi, Ramesh

    2004-01-01

    Cell death/survival following traumatic brain injury (TBI) may be a result of alterations in the intracellular ratio of death and survival factors. Bcl-2 family genes mediate both cell survival and the initiation of cell death. Using lysate RNase protections assays, mRNA expression of the anti-cell death genes Bcl-2 and Bcl-xL, and the pro-cell death gene Bax, was evaluated following experimental brain injuries in adult male Sprague-Dawley rats. Both the lateral fluid-percussion (LFP) and the...

  16. Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats

    Directory of Open Access Journals (Sweden)

    Das Mahasweta

    2011-10-01

    Full Text Available Abstract Background Traumatic brain injury (TBI evokes a systemic immune response including leukocyte migration into the brain and release of pro-inflammatory cytokines; however, the mechanisms underlying TBI pathogenesis and protection are poorly understood. Due to the high incidence of head trauma in the sports field, battlefield and automobile accidents identification of the molecular signals involved in TBI progression is critical for the development of novel therapeutics. Methods In this report, we used a rat lateral fluid percussion impact (LFPI model of TBI to characterize neurodegeneration, apoptosis and alterations in pro-inflammatory mediators at two time points within the secondary injury phase. Brain histopathology was evaluated by fluoro-jade (FJ staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay, polymerase chain reaction (qRT PCR, enzyme linked immunosorbent assay (ELISA and immunohistochemistry were employed to evaluate the CCL20 gene expression in different tissues. Results Histological analysis of neurodegeneration by FJ staining showed mild injury in the cerebral cortex, hippocampus and thalamus. TUNEL staining confirmed the presence of apoptotic cells and CD11b+ microglia indicated initiation of an inflammatory reaction leading to secondary damage in these areas. Analysis of spleen mRNA by PCR microarray of an inflammation panel led to the identification of CCL20 as an important pro-inflammatory signal upregulated 24 h after TBI. Although, CCL20 expression was observed in spleen and thymus after 24h of TBI, it was not expressed in degenerating cortex or hippocampal neurons until 48 h after insult. Splenectomy partially but significantly decreased the CCL20 expression in brain tissues. Conclusion These results demonstrate that the systemic inflammatory reaction to TBI starts earlier than the local brain response and suggest that spleen- and/ or thymus-derived CCL20 might play a role in

  17. Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.

    Directory of Open Access Journals (Sweden)

    Joon W Shim

    Full Text Available Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2 that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive control, and a 90-min tail suspension was used as a stress (negative control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC, ventromedial hypothalamus (VMH, and brain stem (BS. We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.

  18. Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

    Science.gov (United States)

    Eising, Else; Huisman, Sjoerd M H; Mahfouz, Ahmed; Vijfhuizen, Lisanne S; Anttila, Verneri; Winsvold, Bendik S; Kurth, Tobias; Ikram, M Arfan; Freilinger, Tobias; Kaprio, Jaakko; Boomsma, Dorret I; van Duijn, Cornelia M; Järvelin, Marjo-Riitta R; Zwart, John-Anker; Quaye, Lydia; Strachan, David P; Kubisch, Christian; Dichgans, Martin; Davey Smith, George; Stefansson, Kari; Palotie, Aarno; Chasman, Daniel I; Ferrari, Michel D; Terwindt, Gisela M; de Vries, Boukje; Nyholt, Dale R; Lelieveldt, Boudewijn P F; van den Maagdenberg, Arn M J M; Reinders, Marcel J T

    2016-04-01

    Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology. PMID:26899160

  19. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2011-03-01

    Full Text Available Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark phase. Conclusion Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

  20. Expression weighted cell type enrichments reveal genetic and cellular nature of major brain disorders

    Directory of Open Access Journals (Sweden)

    Nathan Gerald Skene

    2016-01-01

    Full Text Available The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer’s disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer’s and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesised that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer’s disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models.

  1. Brain stem global gene expression profiles in human spina bifida embryos

    Institute of Scientific and Technical Information of China (English)

    Hong Zhao; Xiang Li; Wan-I Lie; Quanren He; Ting Zhang; Xiaoying Zheng; Ran Zhou; Jun Xie

    2011-01-01

    Environmental and genetic factors influence the occurrence of neural tube defects, such as spina bifida.Specific disease expression patterns will help to elucidate the pathogenesis of disease.However, results obtained from animal models, which often exhibit organism specificity, do not fully explain the mechanisms of human spina bifida onset.In the present study, three embryos with a gestational age of approximately 17 weeks and a confirmed diagnosis of spina bifida, as well as 3 age-matched normal embryos, were obtained from abortions.Fetal brain stem tissues were dissected for RNA isolation, and microarray analyses were conducted to examine profiles of gene expression in brain stems of spina bifida and normal embryos using Affymetrix HG-U1 33A 2.0 GeneChip arrays.Of the 14 500 gene transcripts examined, a total of 182 genes exhibited at least 2.5-fold change in expression, including 140 upregulated and 42 downregulated genes.These genes were placed into 19 main functional categories according to the Gene Ontology Consortium database for biological functions.Of the 182 altered genes, approximately 50% were involved in cellular apoptosis, growth, adhesion, cell cycle, stress, DNA replication and repair, signal transduction, nervous system development, oxidoreduction, immune responses, and regulation of gene transcription.Gene expression in multiple biological pathways was altered in the brain stem of human spina bifida embryos.

  2. Sex-dependent gene expression in early brain development of chicken embryos

    Directory of Open Access Journals (Sweden)

    Stigson Michael

    2006-02-01

    Full Text Available Abstract Background Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms. Results Using cDNA microarrays and real-time PCR we found gene expression differences between the male and female embryonic brain (or whole head that may be independent of morphological differentiation of the gonads. Genes located on the sex chromosomes (ZZ in males and ZW in females were common among the differentially expressed genes, several of which (WPKCI-8, HINT, MHM non-coding RNA have previously been implicated in avian sex determination. A majority of the identified genes were more highly expressed in males. Three of these genes (CDK7, CCNH and BTF2-P44 encode subunits of the transcription factor IIH complex, indicating a role for this complex in neuronal differentiation. Conclusion In conclusion, this study provides novel insights into sexually dimorphic gene expression in the embryonic chicken brain and its possible involvement in sex differentiation of the nervous system in birds.

  3. Quality control parameters on a large dataset of regionally dissected human control brains for whole genome expression studies

    OpenAIRE

    Trabzuni, Daniah; Ryten, Mina; Walker, Robert; Smith, Colin; Imran, Sabaena; Ramasamy, Adaikalavan; Weale, Michael E; Hardy, John

    2011-01-01

    We are building an open-access database of regional human brain expression designed to allow the genome-wide assessment of genetic variability on expression. Array and RNA sequencing technologies make assessment of genome-wide expression possible. Human brain tissue is a challenging source for this work because it can only be obtained several and variable hours post-mortem and after varying agonal states. These variables alter RNA integrity in a complex manner. In this report, we assess the e...

  4. Sample matching by inferred agonal stress in gene expression analyses of the brain

    Directory of Open Access Journals (Sweden)

    Bunney William E

    2007-09-01

    Full Text Available Abstract Background Gene expression patterns in the brain are strongly influenced by the severity and duration of physiological stress at the time of death. This agonal effect, if not well controlled, can lead to spurious findings and diminished statistical power in case-control comparisons. While some recent studies match samples by tissue pH and clinically recorded agonal conditions, we found that these indicators were sometimes at odds with observed stress-related gene expression patterns, and that matching by these criteria still sometimes results in identifying case-control differences that are primarily driven by residual agonal effects. This problem is analogous to the one encountered in genetic association studies, where self-reported race and ethnicity are often imprecise proxies for an individual's actual genetic ancestry. Results We developed an Agonal Stress Rating (ASR system that evaluates each sample's degree of stress based on gene expression data, and used ASRs in post hoc sample matching or covariate analysis. While gene expression patterns are generally correlated across different brain regions, we found strong region-region differences in empirical ASRs in many subjects that likely reflect inter-individual variabilities in local structure or function, resulting in region-specific vulnerability to agonal stress. Conclusion Variation of agonal stress across different brain regions differs between individuals, revealing a new level of complexity for gene expression studies of brain tissues. The Agonal Stress Ratings quantitatively assess each sample's extent of regulatory response to agonal stress, and allow a strong control of this important confounder.

  5. Nutritionally driven differential gene expression leads to heterochronic brain development in honeybee castes.

    Science.gov (United States)

    Moda, Lívia Maria; Vieira, Joseana; Guimarães Freire, Anna Cláudia; Bonatti, Vanessa; Bomtorin, Ana Durvalina; Barchuk, Angel Roberto; Simões, Zilá Luz Paulino

    2013-01-01

    The differential feeding regimes experienced by the queen and worker larvae of the honeybee Apis mellifera shape a complex endocrine response cascade that ultimately gives rise to differences in brain morphologies. Brain development analyzed at the morphological level from the third (L3) through fifth (L5) larval instars revealed an asynchrony between queens and workers. In the feeding phase of the last larval instar (L5F), two well-formed structures, pedunculi and calyces, are identifiable in the mushroom bodies of queens, both of which are not present in workers until a later phase (spinning phase, L5S). Genome-wide expression analyses and normalized transcript expression experiments monitoring specific genes revealed that this differential brain development starts earlier, during L3. Analyzing brains from L3 through L5S1 larvae, we identified 21 genes with caste-specific transcription patterns (e.g., APC-4, GlcAT-P, fax, kr-h1 and shot), which encode proteins that are potentially involved in the development of brain tissues through controlling the cell proliferation rate (APC4, kr-h1) and fasciculation (GlcAT-P, fax, and shot). Shot, whose expression is known to be required for axon extension and cell proliferation, was found to be transcribed at significantly higher levels in L4 queens compared with worker larvae. Moreover, the protein encoded by this gene was immunolocalized to the cytoplasm of cells near the antennal lobe neuropiles and proximal to the Kenyon cells in the brains of L4 queens. In conclusion, during the larval period, the brains of queens are larger and develop more rapidly than workers' brains, which represents a developmental heterochrony reflecting the effect of the differential feeding regime of the two castes on nervous system development. Furthermore, this differential development is characterized by caste-specific transcriptional profiles of a set of genes, thus pointing to a link between differential nutrition and differential

  6. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer’s Disease Affected Brain Regions

    Science.gov (United States)

    Berretta, Regina; Moscato, Pablo

    2016-01-01

    Background Alzheimer’s disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. Methods The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. Results We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD

  7. Maternal zinc deficiency impairs brain nestin expression in prenatal and postnatal mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice.From d 1 of pregnancy(E0)until postnatal d 20(P20),maternal mice were fed experimental diets that contained 1 mg Zn/kg/day(severe zinc deficient,SZD),5 mg Zn/kg/day(marginal zinc deficient,MZD),30 mg Zn/kg/day(zinc adequately supplied,ZA)or 100 mg Zn/kg/day(zinc supplemented,ZS and pair-fed,PF).Brains of offspring from these dietary groups were examined at various developmental stages for expression of nestin,an intermediate filament protein found in neural stem cells and young neurons,Immunocytochemistry showed nestin expression in neural tube 10.5 d post citrus(dpc)as well as in the cerebral cortex and neural tube from 10.5 dpc to postnatal d 10(P10).Nestin immunoreactivities in both brain and neural tube of those zinc-supplemented control groups(ZA,ZS,PF)were stronger than those in zinc-deficient groups(SZD and MZD).Western blot analysis confirmed that nestin levels in pooled brain extracts from each of the zinc-supplemented groups(ZA,ZS,PF)were much higher than those from the zinc-deficient groups(SZD and MZD)from 10.5 dpc to P10.Immunostaining and Western blots showed no detectable nestin in any of the experimental and control group brains after P20.These observations of an association between maternal zinc deficiency and decreased nestin protein levels in brains of offspring suggest that zinc deficiency suppresses development of neural stem cells,an effect which may lead to neuroanatomical and behavioral abnormalities in adults.

  8. Species differences in brain gene expression profiles associated with adult behavioral maturation in honey bees

    Directory of Open Access Journals (Sweden)

    Robinson Gene E

    2007-06-01

    Full Text Available Abstract Background Honey bees are known for several striking social behaviors, including a complex pattern of behavioral maturation that gives rise to an age-related colony division of labor and a symbolic dance language, by which successful foragers communicate the location of attractive food sources to their nestmates. Our understanding of honey bees is mostly based on studies of the Western honey bee, Apis mellifera, even though there are 9–10 other members of genus Apis, showing interesting variations in social behavior relative to A. mellifera. To facilitate future in-depth genomic and molecular level comparisons of behavior across the genus, we performed a microarray analysis of brain gene expression for A. mellifera and three key species found in Asia, A. cerana, A. florea and A. dorsata. Results For each species we compared brain gene expression patterns between foragers and adult one-day-old bees on an A. mellifera cDNA microarray and calculated within-species gene expression ratios to facilitate cross-species analysis. The number of cDNA spots showing hybridization fluorescence intensities above the experimental threshold was reduced by an average of 16% in the Asian species compared to A. mellifera, but an average of 71% of genes on the microarray were available for analysis. Brain gene expression profiles between foragers and one-day-olds showed differences that are consistent with a previous study on A. mellifera and were comparable across species. Although 1772 genes showed significant differences in expression between foragers and one-day-olds, only 218 genes showed differences in forager/one-day-old expression between species (p Conclusion We conclude that the A. mellifera cDNA microarray can be used effectively for cross-species comparisons within the genus. Our results indicate that there is a widespread conservation of the molecular processes in the honey bee brain underlying behavioral maturation. Species differences in

  9. Gene expression profiling following maternal deprivation: Involvement of the brain renin-angiotensin system

    Directory of Open Access Journals (Sweden)

    Wolfgang Wurst

    2009-05-01

    Full Text Available The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP, where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differentially regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently up-regulated genes, angiotensinogen, was validated using in-situ hybridization. Angiotensinogen is the precursor of angiotensin II, the main effector of the brain renin-angiotensin system (RAS, which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1 antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain a nd ACTH release following maternal separation. AT(1 receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and contribute to identifying signaling cascades that control stress system activity in the neonate.

  10. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

    Directory of Open Access Journals (Sweden)

    Carl O Olson

    Full Text Available MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum, whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute

  11. Fluid-percussion brain injury induces changes in aquaporin channel expression.

    Science.gov (United States)

    Oliva, A A; Kang, Y; Truettner, J S; Sanchez-Molano, J; Furones, C; Yool, A J; Atkins, C M

    2011-04-28

    Edema, the accumulation of excess fluid, is a major pathological change in the brain that contributes significantly to pathology and mortality after moderate to severe brain injury. Edema is regulated by aquaporin (AQP) channels which transport water across cellular membranes. Six AQPs are found in the brain (1, 3, 4, 5, 8, and 9), and previous studies have found that AQP4 is regulated after traumatic brain injury (TBI). To further understand how AQPs contribute to brain edema, we investigated whether expression of AQP1, 3, and 9 are also regulated after TBI. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury (FPI) or sham surgery. After induction of FPI, the injured, ipsilateral parietal cortex and hippocampus were dissected and analyzed by Western blotting. We observed a small decrease in AQP3 and 4 levels at 7 days after FPI in the ipsilateral, parietal cortex. Both AQP1 and 9 significantly increased within 30 min post-injury and remained elevated for up to 6 h in the ipsilateral, parietal cortex. Aqp1 and 9 mRNA levels were also significantly increased at 30 min post-FPI. Administration of an AQP1 and 4 antagonist, AqB013, non-significantly increased brain water content in sham, non-injured animals, and did not prevent edema formation 24 h after trauma in either the parietal cortex or hippocampus. These results indicate that Aqp1 and 9 mRNA and protein levels increase after moderate parasagittal FPI and that an inhibitor of AQP1 and 4 does not decrease edema after moderate parasagittal FPI. PMID:21329742

  12. Generation and Purification of Human INO80 Chromatin Remodeling Complexes and Subcomplexes

    OpenAIRE

    Chen, Lu; Ooi, Soon-Keat; Conaway, Ronald C.; Conaway, Joan W

    2014-01-01

    INO80 chromatin remodeling complexes regulate nucleosome dynamics and DNA accessibility by catalyzing ATP-dependent nucleosome remodeling. Human INO80 complexes consist of 14 protein subunits including Ino80, a SNF2-like ATPase, which serves both as the catalytic subunit and the scaffold for assembly of the complexes. Functions of the other subunits and the mechanisms by which they contribute to the INO80 complex's chromatin remodeling activity remain poorly understood, in part due to the cha...

  13. MMP-2/MMP-9 plasma level and brain expression in cerebral amyloid angiopathy-associated hemorrhagic stroke.

    Science.gov (United States)

    Hernandez-Guillamon, Mar; Martinez-Saez, Elena; Delgado, Pilar; Domingues-Montanari, Sophie; Boada, Cristina; Penalba, Anna; Boada, Mercè; Pagola, Jorge; Maisterra, Olga; Rodriguez-Luna, David; Molina, Carlos A; Rovira, Alex; Alvarez-Sabin, José; Ortega-Aznar, Arantxa; Montaner, Joan

    2012-03-01

    Cerebral amyloid angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly. Matrix metalloproteinases (MMPs) have been implicated in blood-brain barrier disruption and ICH pathogenesis. In this study, we determined the levels MMP-2 and MMP-9 in plasma and their brain expression in CAA-associated hemorrhagic stroke. Although MMP-2 and MMP-9 plasma levels did not differ among patients and controls, their brain expression was increased in perihematoma areas of CAA-related hemorrhagic strokes compared with contralateral areas and nonhemorrhagic brains. In addition, MMP-2 reactivity was found in β-amyloid (Aβ)-damaged vessels located far from the acute ICH and in chronic microbleeds. MMP-2 expression was associated to endothelial cells, histiocytes and reactive astrocytes, whereas MMP-9 expression was restricted to inflammatory cells. In summary, MMP-2 expression within and around Aβ-compromised vessels might contribute to the vasculature fatal fate, triggering an eventual bleeding. PMID:21707819

  14. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

    OpenAIRE

    Martinowich Keri; Schloesser Robert J; Jimenez Dennisse V; Weinberger Daniel R; Lu Bai

    2011-01-01

    Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF) in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivat...

  15. Gene Expression Profiling Following Maternal Deprivation: Involvement of the Brain Renin-Angiotensin System

    OpenAIRE

    Liebl, Claudia; Panhuysen, Markus; Pütz, Benno; Trümbach, Dietrich; Wurst, Wolfgang; Deussing, Jan M.; Müller, Marianne B.; Schmidt, Mathias V.

    2009-01-01

    The postnatal development of the mouse is characterized by a stress hypo-responsive period (SHRP), where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricu...

  16. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

    OpenAIRE

    Wang, Qiong; Shao, Feng; Wang, Weiwen

    2015-01-01

    Early life adversity, such as postnatal maternal separation (MS), play a central role in the development of psychopathologies during individual ontogeny. In this study, we investigated the effects of repeated MS (4 h per day from postnatal day (PND) 1–21) on the brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc) and the hippocampus of male and female juvenile (PND 21), adolescent (PND 35) and young adult (PND 56) Wistar rats...

  17. Gene expression profiling following maternal deprivation: Involvement of the brain renin-angiotensin system

    OpenAIRE

    Wolfgang Wurst; Deussing, Jan M.

    2009-01-01

    The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP), where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricul...

  18. Gene expression patterns in primary neuronal clusters of the Drosophila embryonic brain

    OpenAIRE

    Sprecher, Simon G.; Reichert, Heinrich; Hartenstein, Volker

    2007-01-01

    The brain of Drosophila is formed by approximately 100 lineages, each lineage being derived from a stem cell-like neuroblast that segregates from the procephalic neurectoderm of the early embryo. A neuroblast map has been established in great detail for the early embryo, and a suite of molecular markers has been defined for all neuroblasts included in this map (Urbach and Technau, 2003a). However, the expression of these markers was not followed into later embryonic or larval stages, mainly d...

  19. Main subunits of ionotropic glutamate receptors are expressed in isolated rat brain microvessels

    Czech Academy of Sciences Publication Activity Database

    Šťastný, František; Schwendt, M.; Lisý, Václav; Ježová, D.

    2002-01-01

    Roč. 24, č. 1 (2002), s. 93-96. ISSN 0161-6412 R&D Projects: GA ČR GA305/99/1317; GA ČR GA309/99/0211 Grant ostatní: VEGA(SK) 2/6084 Institutional research plan: CEZ:AV0Z5011922 Keywords : Glutamate receptor * gene expression and binding * blood-brain barrier Subject RIV: FH - Neurology Impact factor: 0.969, year: 2002

  20. Differential gene expression in brain tissues of aggressive and non-aggressive dogs

    OpenAIRE

    Tverdal Aage; Arnet Ellen; Bønsdorff Tina B; Våge Jørn; Lingaas Frode

    2010-01-01

    Abstract Background Canine behavioural problems, in particular aggression, are important reasons for euthanasia of otherwise healthy dogs. Aggressive behaviour in dogs also represents an animal welfare problem and a public threat. Elucidating the genetic background of adverse behaviour can provide valuable information to breeding programs and aid the development of drugs aimed at treating undesirable behaviour. With the intentions of identifying gene-specific expression in particular brain pa...

  1. Simultaneous and long-term measurement of gene expression and neuronal activity from a brain slice

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Daisuke Ono, Ken-ichi Honma & Sato Honma ### Abstract Photonic bioimaging is a powerful tool for measurement of biological functions in living cells. It enables us to identify when, how, and where a phenomenon of interest takes place such as gene expression and interaction of molecules. To understand the sequential events happening in the brain, it is of special importance to assess more than one parameter simultaneously. In this protocol, we describe detailed methods of ...

  2. Reduction of Photo Bleaching and Long Term Archiving of Chemically Cleared GFP-Expressing Mouse Brains

    OpenAIRE

    Klaus Becker; Christian Markus Hahn; Saiedeh Saghafi; Nina Jährling; Martina Wanis; Hans-Ulrich Dodt

    2014-01-01

    Tissue clearing allows microscopy of large specimens as whole mouse brains or embryos. However, lipophilic tissue clearing agents as dibenzyl ether limit storage time of GFP-expressing samples to several days and do not prevent them from photobleaching during microscopy. To preserve GFP fluorescence, we developed a transparent solid resin formulation, which maintains the specimens' transparency and provides a constant signal to noise ratio even after hours of continuous laser irradiation. If ...

  3. Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures

    DEFF Research Database (Denmark)

    Zimmer, J; Kristensen, Bjarne Winther; Jakobsen, B; Noraberg, J

    2000-01-01

    -induced excitotoxicity and KA-glutamate receptor subunit mRNA expression after long-term exposure to low, non-toxic doses of KA and NBQX. We conclude that organotypic brain slice cultures, combined with standardized procedures for quantitation of cell damage and receptor subunit changes is of great potential use for...... studies of excitotoxic, glutamate receptor-induced neuronal cell death, receptor modulation and related neuroprotection....

  4. Maternal Treatment with Glucocorticoids Modulates Gap Junction Protein Expression in the Ovine Fetal Brain

    OpenAIRE

    Sadowska, Grazyna B.; Stonestreet, Barbara S

    2014-01-01

    Gap junctions facilitate intercellular communication and are important in brain development. Connexins (Cx) comprise a transmembrane protein family that forms gap junctions. Cx-32 is expressed in oligodendrocytes and neurons, Cx-36 in neurons, and Cx-43 in astrocytes. Although single antenatal steroid courses are recommended for fetal lung maturation, multiple courses can be given to women at recurrent risk for premature delivery. We examined the effects of single and multiple glucocorticoid ...

  5. Proinflammatory cytokine expression contributes to brain injury provoked by chronic monocyte activation.

    OpenAIRE

    Sirén, A. L.; McCarron, R.; Wang, L.; Garcia-Pinto, P.; Ruetzler, C.; Martin, D.; Hallenbeck, J. M.

    2001-01-01

    BACKGROUND: We have proposed that an increased interaction between monocyte/macrophages and blood vessel endothelium predisposes subjects to strokes. The effect of chronic monocyte activation on the development of cerebral infarcts was thus studied in rats after provocation of a modified local Swartzman reaction, in brain vasculature. MATERIALS AND METHODS: Two weeks after an IV bolus of bacillus Calmette-Guérin (BCG), we studied spontaneous superoxide production, integrin expression, endothe...

  6. Natural selection constrains personality and brain gene expression differences in Atlantic salmon (Salmo salar)

    DEFF Research Database (Denmark)

    Thörnqvist, Per-Ove; Höglund, Erik; Winberg, Svante

    2015-01-01

    littermates. Taken together, these results suggest that time of emergence, boldness and aggression are linked to each other, forming a behavioural syndrome in juvenile salmon. Differences in brain gene expression between early and late emerging salmon add further support to a relationship between stress...... and more aggressive. In the present study, emerging Atlantic salmon (Salmo salar L.) alevins were sorted into three fractions: early, intermediate and late emerging. At the parr stage, behaviour, stress responses, hindbrain monoaminergic activity and forebrain gene expression were explored in fish...

  7. Expression of Transcripts for Myelin Related Genes in Postmortem Brain from Cocaine Abusers

    OpenAIRE

    Kristiansen, Lars V.; Meador-Woodruff, James H.; Bannon, Michael J.

    2008-01-01

    Chronic abuse of cocaine is known to cause neuroadaptive changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). In addition, altered expression of the myelin-related genes MBP, MOBP, PLP1 as well as of MAL2 in NAc was recently reported by gene array analysis in brains from cocaine abusers. In the present study we used in situ hybridization to quantify transcript expression of these four genes, as well as for the myelin-related transcripts encoding quaking, EDG2, claudin-11, ...

  8. Global analysis of gene expression in the developing brain of Gtf2ird1 knockout mice.

    Directory of Open Access Journals (Sweden)

    Jennifer O'Leary

    Full Text Available BACKGROUND: Williams-Beuren Syndrome (WBS is a neurodevelopmental disorder caused by a hemizygous deletion of a 1.5 Mb region on chromosome 7q11.23 encompassing 26 genes. One of these genes, GTF2IRD1, codes for a putative transcription factor that is expressed throughout the brain during development. Genotype-phenotype studies in patients with atypical deletions of 7q11.23 implicate this gene in the neurological features of WBS, and Gtf2ird1 knockout mice show reduced innate fear and increased sociability, consistent with features of WBS. Multiple studies have identified in vitro target genes of GTF2IRD1, but we sought to identify in vivo targets in the mouse brain. METHODOLOGY/PRINCIPAL FINDINGS: We performed the first in vivo microarray screen for transcriptional targets of Gtf2ird1 in brain tissue from Gtf2ird1 knockout and wildtype mice at embryonic day 15.5 and at birth. Changes in gene expression in the mutant mice were moderate (0.5 to 2.5 fold and of candidate genes with altered expression verified using real-time PCR, most were located on chromosome 5, within 10 Mb of Gtf2ird1. siRNA knock-down of Gtf2ird1 in two mouse neuronal cell lines failed to identify changes in expression of any of the genes identified from the microarray and subsequent analysis showed that differences in expression of genes on chromosome 5 were the result of retention of that chromosome region from the targeted embryonic stem cell line, and so were dependent upon strain rather than Gtf2ird1 genotype. In addition, specific analysis of genes previously identified as direct in vitro targets of GTF2IRD1 failed to show altered expression. CONCLUSIONS/SIGNIFICANCE: We have been unable to identify any in vivo neuronal targets of GTF2IRD1 through genome-wide expression analysis, despite widespread and robust expression of this protein in the developing rodent brain.

  9. Preliminary observation of genes specifically expressed in brain tissues during stroke-like episodes in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Xian-mei; ZHAO Bin; ZHU Shan-jun; ZHU Zhi-ming; ZHANG Qian; HUI Ru-tai

    2001-01-01

    Objective: To observe the difference of gene expressions of brain tissues during apoplectic episodes and those of normal brain in Wistar rats in order to study the pathological mechanism of apoplexy. Methods: A rat model of hypertension was established with the administration of cold stimulus and high salt intake as the environmental risk factors.Apoplexy occurred in the rats because of hypertension. Suppression subtractive hybridization(SSH) was used to identify and analyze the differential genes specifically expressed in cerebral tissues of stoke group and control rats. Results: A total of 226 genes out of the 228 were usable and analyzed. The average length of the 226 genes was (286.6±120.3) bp with a range from 50 bp to 619 bp. And 126 clones out of the 226 showed a sequence with significant identity to the known genes; 78 clones demonstrated homogenous sequences to the existing ESTs ofdbEST, but no one of the 78 showed sequence with identity to that of known genes; and remaining 22 were novel transrcipts exhibiting no similarity to any known sequences. All the clones which were highly homogenous to the known genes were categorized on the basis of their function. It was found that 26.5% of the mitochodrial genes in brain tissues underwent changes after apoplexy and the changes showed a twofold relationship of cause and effect. Conclusion: Environmental factors are able to induce changes of gene expression, which may increase the sensitivity to apoplectic stroke.

  10. Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

    Science.gov (United States)

    Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

    2012-04-01

    The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p LD(50) VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure. PMID:22240983

  11. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  12. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    International Nuclear Information System (INIS)

    Highlights: → The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. → The level of colocalization is similar in the male and female brain. → Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. → Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  13. Increased expression of neurotrophin 4 following focal cerebral ischemia in adult rat brain with treadmill exercise.

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    Full Text Available Neurotrophin 4 (NT-4 belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF, because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

  14. Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

    Directory of Open Access Journals (Sweden)

    Stefan Koelsch

    Full Text Available BACKGROUND: There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: This study investigates event-related brain potentials (ERPs, skin conductance responses (SCRs and heart rate (HR elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression, we also created versions without variations in tempo and loudness (without musical expression to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing and an N5 (reflecting processing of meaning information in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses. The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function differed between the expressive and the non-expressive condition. CONCLUSIONS/SIGNIFICANCE: These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

  15. Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors.

    Directory of Open Access Journals (Sweden)

    Pantelis Stavrinou

    Full Text Available Endogenous and exogenous compounds as well as carcinogens are metabolized and detoxified by phase I and II enzymes, the activity of which could be crucial to the inactivation and hence susceptibility to carcinogenic factors. The expression of these enzymes in human brain tumor tissue has not been investigated sufficiently. We studied the association between tumor pathology and the expression profile of seven phase I and II drug metabolizing genes (CYP1A1, CYP1B1, ALDH3A1, AOX1, GSTP1, GSTT1 and GSTM3 and some of their proteins.Using qRT-PCR and western blotting analysis the gene and protein expression in a cohort of 77 tumors were investigated. The major tumor subtypes were meningioma, astrocytoma and brain metastases, -the later all adenocarcinomas from a lung primary.Meningeal tumors showed higher expression levels for AOX1, CYP1B1, GSTM3 and GSTP1. For AOX1, GSTM and GSTP1 this could be verified on a protein level as well. A negative correlation between the WHO degree of malignancy and the strength of expression was identified on both transcriptional and translational level for AOX1, GSTM3 and GSTP1, although the results could have been biased by the prevalence of meningiomas and glioblastomas in the inevitably bipolar distribution of the WHO grades. A correlation between the gene expression and the protein product was observed for AOX1, GSTP1 and GSTM3 in astrocytomas.The various CNS tumors show different patterns of drug metabolizing gene expression. Our results suggest that the most important factor governing the expression of these enzymes is the histological subtype and to a far lesser extent the degree of malignancy itself.

  16. Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury

    Science.gov (United States)

    Ott, Christoph; Martens, Henrik; Hassouna, Imam; Oliveira, Bárbara; Erck, Christian; Zafeiriou, Maria-Patapia; Peteri, Ulla-Kaisa; Hesse, Dörte; Gerhart, Simone; Altas, Bekir; Kolbow, Tekla; Stadler, Herbert; Kawabe, Hiroshi; Zimmermann, Wolfram-Hubertus; Nave, Klaus-Armin; Schulz-Schaeffer, Walter; Jahn, Olaf; Ehrenreich, Hannelore

    2015-01-01

    Erythropoietin (EPO) exerts potent neuroprotective, neuroregenerative and procognitive functions. However, unequivocal demonstration of erythropoietin receptor (EPOR) expression in brain cells has remained difficult since previously available anti-EPOR antibodies (EPOR-AB) were unspecific. We report here a new, highly specific, polyclonal rabbit EPOR-AB directed against different epitopes in the cytoplasmic tail of human and murine EPOR and its characterization by mass spectrometric analysis of immuno-precipitated endogenous EPOR, Western blotting, immunostaining and flow cytometry. Among others, we applied genetic strategies including overexpression, Lentivirus-mediated conditional knockout of EpoR and tagged proteins, both on cultured cells and tissue sections, as well as intracortical implantation of EPOR-transduced cells to verify specificity. We show examples of EPOR expression in neurons, oligodendroglia, astrocytes and microglia. Employing this new EPOR-AB with double-labeling strategies, we demonstrate membrane expression of EPOR as well as its localization in intracellular compartments such as the Golgi apparatus. Moreover, we show injury-induced expression of EPOR. In mice, a stereotactically applied stab wound to the motor cortex leads to distinct EpoR expression by reactive GFAP-expressing cells in the lesion vicinity. In a patient suffering from epilepsy, neurons and oligodendrocytes of the hippocampus strongly express EPOR. To conclude, this new analytical tool will allow neuroscientists to pinpoint EPOR expression in cells of the nervous system and to better understand its role in healthy conditions, including brain development, as well as under pathological circumstances, such as upregulation upon distress and injury. PMID:26349059

  17. Naoxintong dose effects on inflammatory factor expression in the rat brain following focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Xiangjian Zhang; Li Xü; Zuoran Chen; Shuchao Hu; Liying Zhang; Haiyan Li; Ruichun Liu

    2008-01-01

    BACKGROUND: Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury.OBJECTIVE: To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B (κ B), interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia.DESIGN, TIME AND SETTING: The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIAIS: A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320 g, were selected. Naoxintong powder (mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis) was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608.METHODS: The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 glkg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage. All rats were administered by garage at 5 and 23 hours following surgery, and subsequently, once per day.MAIN OUTCOME MEASURES: At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- κB, interleukin-6, tumor necrosis factor-α, and complement 3 was examined by immunohistochemistry.RESULTS: A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as

  18. Netrin-5 is highly expressed in neurogenic regions of the adult brain.

    Directory of Open Access Journals (Sweden)

    Satoru eYamagishi

    2015-04-01

    Full Text Available Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb, rostral migrate stream (RMS, the subventricular zone (SVZ, and the subgranular zone (SGZ of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX-positive neuroblasts, but not in GFAP-positive astrocytes. In the olfactory bulb, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

  19. Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

    OpenAIRE

    Dawson, N.; Kurihara, M.; Thomson, D. M.; Winchester, C L; McVie, A.; Hedde, J.R.; Randall, A.D.; Shen, S.; Seymour, P.A.; Hughes, Z.A.; Dunlop, J; Brown, J.T.; Brandon, N. J.; Morris, B J; Pratt, J.A.

    2015-01-01

    Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the...

  20. Expression of Organic Anion Transporters 1 and 3 in the Ovine Fetal Brain During the Latter Half of Gestation

    OpenAIRE

    Cousins, Roderick; Charles E. Wood

    2010-01-01

    Development and maturation of the fetal brain is critical for homeostasis in utero, responsiveness to fetal stress and, in ruminants, control of the timing of birth. In the sheep, as in the human, the placenta secretes estrogen and other signaling molecules into both the fetal and maternal blood, molecules whose entry or exit across the blood-brain barrier is likely to be facilitated by transporters. The purpose of this study was to test the hypothesis that the ovine fetal brain expresses org...

  1. Postnatal expression of H1-receptor mRNA in the rat brain: correlation to L-histidine decarboxylase expression and local upregulation in limbic seizures.

    Science.gov (United States)

    Lintunen, M; Sallmen, T; Karlstedt, K; Fukui, H; Eriksson, K S; Panula, P

    1998-07-01

    Histamine is implicated in the regulation of brain functions through three distinct receptors. Endogenous histamine in the brain is derived from mast cells and neurons, but the importance of these two pools during early postnatal development is still unknown. The expression of histamine H1-receptor in the rat brain was examined using in situ hybridization during postnatal development and in adults. For comparison, the expression of L-histidine decarboxylase (HDC) in the two pools was revealed. H1-receptor was evenly expressed throughout the brain on the first postnatal days, but resembled the adult, uneven pattern already on postnatal day 5 (P5). HDC was expressed in both mast cells and tuberomammillary neurons from birth until P5, after which the mast cell expression was no more detectable. In adult rat brain, high or moderate levels of H1-receptor expression were found in the hippocampus, zona incerta, medial amygdaloid nucleus and reticular thalamic nucleus. In most areas of the adult brain the expression of H1-receptor mRNA correlates well with binding data and histaminergic innervation. A notable exception is the hypothalamus, with high fibre density but moderate or low H1-receptor expression. Systemic kainic acid administration induced increased expression of H1-receptor mRNA in the caudate-putamen and dentate gyrus, whereas no change was seen in the hippocampal subfields CA1-CA3 or in the entorhinal cortex 6 h after kainic acid injections. This significant increase supports the concept that histaminergic transmission, through H1-receptor, is involved in the regulation of seizure activity in the brain. PMID:9749757

  2. iNOS+ macrophages: potential alternate and tool for effective tumor therapy

    International Nuclear Information System (INIS)

    Inefficient migration of immune effector cells in the tumor is a major limitation of effective therapy against solid tumors. This is due to immunosuppressive micro environment and impermissive endothelium which protects tumors from immune attack which is attributed to massive infiltration of tumors by macrophages which are known as tumor associated macrophages which are INOSlow, Arginase-1+, Ym-1+, CD206+ (known as M2 or alternatively activated or tumor associated macrophages). Accumulation of M2 has been associated with the poor prognosis in the majority of cancer patients. Radiotherapy has recently been introduced as a potential strategy to improve cancer immunotherapy and tumor immune rejection. This is the only clinically advanced approach for noninvasive, site-specific intervention in cancer patients. Majority of cancer patients are routinely irradiated with therapeutic and high doses of γ-radiations which frequently manifest severe local/systemic acute. Low dose radiation (LDR) on the other hand may provide good alternatives of HDR for avoiding such toxicities. In this line, our pioneer study demonstrated that local/systemic low dose irradiation of tumors (2 Gy) effectively modified tumor micro environment and facilitated infiltration of peripheral immune effectors cells (T-cells) in neuroendocrine tumor of pancreas called insulinoma in RIP1-Tag5 (RT5) mice and primary human pancreatic carcinoma. Such tumor infiltration of T cells remained strictly dependent on iNOS+ peritumoral macrophages. Our study also explicitly revealed that adoptive transfer of iNOS expressing macrophages in unirradiated RIP1-Tag5 (RT5) also offer a promising intervention to establish those populations of macrophages in the tumor tissue that enable therapeutic efficacy of cancer immunotherapy. We here demonstrate the critical role of iNOS+ macrophages in joint regulation of tumor micro environment (angiogenesis) as well as effector T cell recruitment into tumor tissue and successful

  3. Testes and brain gene expression in precocious male and adult maturing Atlantic salmon (Salmo salar

    Directory of Open Access Journals (Sweden)

    Houeix Benoit

    2010-03-01

    Full Text Available Abstract Background The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom-built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult and in the parr-smolt transformation. Results Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down-regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1, which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta-globin and guanine nucleotide binding protein (G protein beta polypeptide 2-like 1 (GNB2L1 were also examined in adult maturing testes. Down-regulation of anti-Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For

  4. Connexin26 expression in brain parenchymal cells demonstrated by targeted connexin ablation in transgenic mice.

    Science.gov (United States)

    Nagy, J I; Lynn, B D; Tress, O; Willecke, K; Rash, J E

    2011-07-01

    Astrocytes are known to express the gap junction forming proteins connexin30 (Cx30) and connexin43 (Cx43), but it has remained controversial whether these cells also express connexin26 (Cx26). To investigate this issue further, we examined immunofluorescence labelling of glial connexins in wild-type vs. transgenic mice with targeted deletion of Cx26 in neuronal and glial cells (Cx26fl/fl:Nestin-Cre mice). The Cx26 antibodies utilized specifically recognized Cx26 and lacked cross reaction with highly homologous Cx30, as demonstrated by immunoblotting and immunofluorescence in Cx26-transfected and Cx30-transfected C6 glioma cells. Punctate immunolabelling of Cx26 with these antibodies was observed in leptomeninges and subcortical brain regions. This labelling was absent in subcortical areas of Cx26fl/fl:Nestin-Cre mice, but persisted in leptomeningeal tissues of these mice, thereby distinguishing localization of Cx26 between parenchymal and non-parenchymal tissue. In subcortical brain parenchyma, Cx26-positive puncta were often co-localized with astrocytic Cx43, and some were localized along astrocyte cell bodies and processes immunolabelled for glial fibrillary acidic protein. Cx26-positive puncta were also co-localized with punctate labelling of Cx47 around oligodendrocyte somata. Comparisons of Cx26 labelling in rodent species revealed a lower density of Cx26-positive puncta and a more restricted distribution in subcortical regions of mouse compared with rat brain, perhaps partly explaining reported difficulties in detection of Cx26 in mouse brain parenchyma using antibodies or Cx26 gene reporters. These results support our earlier observations of Cx26 expression in astrocytes and its ultrastructural localization in individual gap junction plaques formed between astrocytes as well as in heterotypic gap junctions between astrocytes and oligodendrocytes. PMID:21714813

  5. Relationship between AQP4 expression and structural damage to the blood-brain barrier at early stages of traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    LU Hong; LEI Xiao-yan; HU Hui; HE Zhan-ping

    2013-01-01

    Background Although some studies have reported that aquaporin-4 (AQP4) plays an important role in the brain edema after traumatic brain injury (TBI),little is known about the AQP4 expression in the early stage of TBI,or about the correlation between the structural damage to the blood-brain barrier (BBB) and angioedema.The aim of this project was to investigate the relationship between AQP4 expression and damage to the BBB at early stages of TBI.Methods One hundred and twenty healthy adult Wistar rats were randomly divided into two greups:sham operation group (SO) and TBI group.The TBI group was divided into five sub-groups according to the different time intervals:1,3,6,12,and 24 hours.The brains of the animals were taken out at different time points after TBI to measure brain water content.The cerebral edema and BBB changes in structure were examined with an optical microscopy (OM) and transmission electron microscopy (TEM),and the IgG content and AQP4 protein expression in traumatic brain tissue were determined by means of immunohistochemistry and Western blotting.The data were analyzed with SPSS 13.0statistical software.Results In the SO greup,tissue was negative for IgG,and there were no abnormalities in brain water content or AQP4 expression.In the TBI group,brain water content significantly increased at 6 hours and peaked at 24 hours following injury.IgG expression significantly increased from 1 to 6 hours following injury,and remained at a high level at 24 hours.Pathological observation revealed BBB damage at 1 hour following injury.Angioedema appeared at 1 hour,was gradually aggravated,and became obvious at 6 hours.Intracellular edema occurred at 3 hours,with the presence of large glial cell bodies and mitochondrial swelling.These phenomena were aggravated with time and became obvious at 12 hours.In addition,microglial proliferation was visible at 24 hours.AQP4 protein expression were reduced at 1 hour,lowest at 6 hours,and began to increase at 12 hours

  6. Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Pham Serena

    2011-08-01

    Full Text Available Abstract Background Oxidative stress plays an important role in neuronal dysfunction and neuron loss in Alzheimer's brain. Previous studies have reported downregulation of CREB-mediated transcription by oxidative stress and Aβ. The promoter for CREB itself contains cyclic AMP response elements. Therefore, we examined the expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem brain and in cultured rat hippocampal neurons exposed to Aβ aggregates. Results Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse brain revealed decreases in the mRNA levels of CREB and its target, BDNF. Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB levels in hippocampus and cortex. Markers of oxidative stress were detected in transgenic mouse brain and decreased CREB staining was observed in regions showing abundance of astrocytes. There was also an inverse correlation between SDS-extracted Aβ and CREB protein levels in Alzheimer's post-mortem hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase inhibitor, decreased and the active cleaved form of caspase-9, a marker for the intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat primary hippocampal neurons to Aβ fibrils decreased CREB promoter activity. Decrease in CREB mRNA levels in Aβ-treated neurons was reversed by the antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction led to significant protection against Aβ-induced neuronal apoptosis. Conclusions Our findings suggest that chronic downregulation of CREB-mediated transcription results in decrease of CREB content in the hippocampal neurons of AD brain which may contribute to exacerbation of disease progression.

  7. Expression of Npas4 mRNA in telencephalic areas of adult and postnatal mouse brain

    Directory of Open Access Journals (Sweden)

    Ursula H Winzer-Serhan

    2015-11-01

    Full Text Available The transcription factor neuronal PAS domain-containing protein 4 (Npas4 is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON, piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu, septum and basolateral amygdala nucleus (BLA, basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5, transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission.

  8. Expression of ZIC family genes in meningiomas and other brain tumors

    International Nuclear Information System (INIS)

    Zic zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors. Although human ZIC genes are known to be molecular markers for medulloblastomas, their expression in meningioma has not been addressed to date. We examined the mRNA and protein expression of human ZIC1, ZIC2, ZIC3, ZIC4 and ZIC5 genes in meningiomas in comparison to other brain tumors, using RT-PCR, analysis of published microarray data, and immunostaining. ZIC1, ZIC2 and ZIC5 transcript levels in meningiomas were higher than those in whole brain or normal dura mater, whereas all five ZIC genes were abundantly expressed in medulloblastomas. The expression level of ZIC1 in public microarray data was greater in meningiomas classified as World Health Organization Grade II (atypical) than those classified as Grade I (benign). Immunoscreening using anti-ZIC antibodies revealed that 23 out of 23 meningioma cases were ZIC1/2/3/5-immunopositive. By comparison, nuclear staining by the anti-ZIC4 antibody was not observed in any meningioma case, but was strongly detected in all four medulloblastomas. ZIC-positive meningiomas included meningothelial, fibrous, transitional, and psammomatous histological subtypes. In normal meninges, ZIC-like immunoreactivities were detected in vimentin-expressing arachnoid cells both in human and mouse. ZIC1, ZIC2, and ZIC5 are novel molecular markers for meningiomas whereas ZIC4 expression is highly selective for medulloblastomas. The pattern of ZIC expression in both of these tumor types may reflect the properties of the tissues from which the tumors are derived

  9. Effects of visual deprivation during brain development on expression of AMPA receptor subunits in rat’s hippocampus

    Directory of Open Access Journals (Sweden)

    Sayyed Alireza Talaei

    2015-06-01

    Conclusion: Dark rearing of rats during critical period of brain development changes the relative expression and also arrangement of both AMPA receptor subunits, GluR1 and GluR2 in the hippocampus, age dependently.

  10. Reduction of Nfia gene expression and subsequent target genes by binge alcohol in the fetal brain.

    Science.gov (United States)

    Mandal, Chanchal; Park, Ji Hyun; Lee, Hyung Tae; Seo, Hyemyung; Chung, Il Yup; Choi, Ihn Geun; Jung, Kyoung Hwa; Chai, Young Gyu

    2015-06-26

    The objective of the present study was to investigate the changes in gene expression in the fetal brain (forebrain and hippocampus) caused by maternal binge alcohol consumption. Pregnant C57BL/6J mice were treated intragastrically with distilled phosphate-buffered saline (PBS) or ethanol (2.9 g/kg) from embryonic day (ED) 8-12. Microarray analysis revealed that a significant number of genes were altered at ED 18 in the developing brain. Specifically, in hippocampus, nuclear factor one alpha (Nfia) and three N-methyl-D-aspartate (Nmda) receptors (Nmdar1, Nmdar2b, and Nmdar2d) were down-regulated. The transcription factor Nfia controls gliogenesis, cell proliferation and Nmda-induced neuronal survival by regulating the expression of target genes. Some of the Nfia-target gene (Aldh1a, Folh1, Gjb6, Fgf1, Neurod1, Sept4, and Ntsr2) expressions were also altered as expected. These results suggest that the altered expression of Nfia and Nmda receptors may be associated with the etiology of fetal alcohol syndrome (FAS). The data presented in this report will contribute to the understanding of the molecular mechanisms associated with the effects of alcohol in FASD individuals. PMID:25982323

  11. Environmental effects on molecular biomarkers expression in pancreatic and brain cancer

    Science.gov (United States)

    Mensah, Lawrence; Mallidi, Srivalleesha; Massodi, Iqbal; Anbil, Sriram; Mai, Zhiming; Hasan, Tayyaba

    2013-03-01

    A complete understanding of the biological mechanisms regulating devastating disease such as cancer remains elusive. Pancreatic and brain cancers are primary among the cancer types with poor prognosis. Molecular biomarkers have emerged as group of proteins that are preferentially overexpressed in cancers and with a key role in driving disease progression and resistance to chemotherapy. The epidermal growth factor receptor (EGFR), a cell proliferative biomarker is particularly highly expressed in most cancers including brain and pancreatic cancers. The ability of EGFR to sustain prolong cell proliferation is augmented by biomarkers such as Bax, Bcl-XL and Bcl-2, proteins regulating the apoptotic process. To better understand the role and effect of the microenvironment on these biomarkers in pancreatic cancer (PaCa); we analysed two pancreatic tumor lines (AsPc-1 and MiaPaCa-2) in 2D, 3D in-vitro cultures and in orthotopic tumors at different growth stages. We also investigated in patient derived glioblastoma (GBM) tumor cultures, the ability to utilize the EGFR expression to specifically deliver photosensitizer to the cells for photodynamic therapy. Overall, our results suggest that (1) microenvironment changes affect biomarker expression; thereby it is critical to understand these effects prior to designing combination therapies and (2) EGFR expression in tumor cells indeed could serve as a reliable and a robust biomarker that could be used to design targeted and image-guided photodynamic therapy.

  12. Regulation of P-glycoprotein expression in brain capillaries in Huntington's disease and its impact on brain availability of antipsychotic agents risperidone and paliperidone.

    Science.gov (United States)

    Kao, Yu-Han; Chern, Yijuang; Yang, Hui-Ting; Chen, Hui-Mei; Lin, Chun-Jung

    2016-08-01

    Huntington's disease (HD) is a neurodegenerative disease marked by an expanded polyglutamine (polyQ) tract on the huntingtin (HTT) protein that may cause transcriptional dysfunction. This study aimed to investigate the regulation and function of P-glycoprotein, an important efflux transporter, in brain capillaries in HD. The results showed that, compared with the littermate controls, R6/2 HD transgenic mice with the human mutant HTT gene had higher levels of P-glycoprotein mRNA and protein and enhanced NF-κB activity in their brain capillaries. Higher P-glycoprotein expression was also observed in the brain capillaries of human HD patients. Consistent with this enhanced P-glycoprotein expression, brain extracellular levels and brain-to-plasma ratios of the antipsychotic agents risperidone and paliperidone were significantly lower in R6/2 mice than in their littermate controls. Exogenous expression of human mutant HTT protein with expanded polyQ (mHTT-109Q) in HEK293T cells enhanced the levels of P-glycoprotein transcripts and NF-κB activity compared with cells expressing normal HTT-25Q. Treatment with the IKK inhibitor, BMS-345541, decreased P-glycoprotein mRNA level in cells transfected with mHTT-109Q or normal HTT-25Q In conclusion, mutant HTT altered the expression of P-glycoprotein through the NF-κB pathway in brain capillaries in HD and markedly affected the availability of P-glycoprotein substrates in the brain. PMID:26661162

  13. Dynamic, mating-induced gene expression changes in female head and brain tissues of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Stirling Emma J

    2010-10-01

    Full Text Available Abstract Background Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. Results We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. Conclusions Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors.

  14. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

    Directory of Open Access Journals (Sweden)

    Qiong eWang

    2015-09-01

    Full Text Available Early postnatal maternal separation (MS can play an important role in the development of psychopathologies during ontogeny. In the present study, we investigated the effects of repeated MS (4 h per day from postnatal day [PND] 1–21 on the brain-derived neurotrophic factor (BDNF expression in the medial prefrontal cortex (mPFC, the nucleus accumbens (NAc and the hippocampus of male and female juvenile (PND 21, adolescent (PND 35 and young adult (PND 56 Wistar rats. The results indicated that MS increased BDNF in the CA1 and the dentate gyrus (DG of adolescent rats as well as in the DG of young adult rats. However, the expression of BDNF in the mPFC in the young adult rats was decreased by MS. Additionally, in the hippocampus, there was decreased BDNF expression with age in both the MS and socially reared rats. However, in the mPFC, the BDNF expression was increased with age in the socially reared rats; nevertheless, the BDNF expression was significantly decreased in the MS young adult rats. In the NAc, the BDNF expression was increased with age in the male NMS rats, and the young adult female MS rats had less BDNF expression than the adolescent female MS rats. The

  15. Properties and Expression of Na+/K+-ATPase α-Subunit Isoforms in the Brain of the Swamp Eel, Monopterus albus, Which Has Unusually High Brain Ammonia Tolerance

    OpenAIRE

    Xiu L Chen; Wee, Nicklaus L. J. E.; Hiong, Kum C.; Ong, Jasmine L. Y.; Chng, You R.; Ching, Biyun; Wai P Wong; Shit F Chew; Ip, Yuen K.

    2013-01-01

    The swamp eel, Monopterus albus, can survive in high concentrations of ammonia (>75 mmol l−1) and accumulate ammonia to high concentrations in its brain (∼4.5 µmol g−1). Na+/K+-ATPase (Nka) is an essential transporter in brain cells, and since NH4 + can substitute for K+ to activate Nka, we hypothesized that the brain of M. albus expressed multiple forms of Nka α-subunits, some of which might have high K+ specificity. Thus, this study aimed to clone and sequence the nka α-subunits from the br...

  16. Properties and expression of Na+/K+-ATPase α-subunit isoforms in the brain of the swamp eel, Monopterus albus, which has unusually high brain ammonia tolerance.

    Directory of Open Access Journals (Sweden)

    Xiu L Chen

    Full Text Available The swamp eel, Monopterus albus, can survive in high concentrations of ammonia (>75 mmol l(-1 and accumulate ammonia to high concentrations in its brain (4.5 µmol g(-1. Na(+/K(+-ATPase (Nka is an essential transporter in brain cells, and since NH4(+ can substitute for K(+ to activate Nka, we hypothesized that the brain of M. albus expressed multiple forms of Nka α-subunits, some of which might have high K(+ specificity. Thus, this study aimed to clone and sequence the nka α-subunits from the brain of M. albus, and to determine the effects of ammonia exposure on their mRNA expression and overall protein abundance. The effectiveness of NH4(+ to activate brain Nka from M. albus and Mus musculus was also examined by comparing their Na(+/K(+-ATPase and Na(+/NH4(+-ATPase activities over a range of K(+/NH4(+ concentrations. The full length cDNA coding sequences of three nkaα (nkaα1, nkaα3a and nkaα3b were identified in the brain of M. albus, but nkaα2 expression was undetectable. Exposure to 50 mmol l(-1 NH4Cl for 1 day or 6 days resulted in significant decreases in the mRNA expression of nkaα1, nkaα3a and nkaα3b. The overall Nka protein abundance also decreased significantly after 6 days of ammonia exposure. For M. albus, brain Na(+/NH4(+-ATPase activities were significantly lower than the Na(+/K(+-ATPase activities assayed at various NH4(+/K(+ concentrations. Furthermore, the effectiveness of NH4(+ to activate Nka from the brain of M. albus was significantly lower than that from the brain of M. musculus, which is ammonia-sensitive. Hence, the (1 lack of nkaα2 expression, (2 high K(+ specificity of K(+ binding sites of Nkaα1, Nkaα3a and Nkaα3b, and (3 down-regulation of mRNA expression of all three nkaα isoforms and the overall Nka protein abundance in response to ammonia exposure might be some of the contributing factors to the high brain ammonia tolerance in M. albus.

  17. Differential expression of Egr1 and activation of microglia following irradiation in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Vollmann, H.; Woelfel, S.; Meyermann, R. [Tuebingen Univ. (Germany). Inst. of Brain Research; Ohneseit, P. [Tuebingen Univ. (Germany). Div. of Radiobiology and Molecular Environmental Research; Stransky, E. [Tuebingen Univ. (Germany). Dept. of Psychiatry; Vonthein, R. [Tuebingen Univ. (Germany). Dept. of Medical Biometry; Wick, W. [Tuebingen Univ. (Germany). Dept. of General Neurology; Simon, P. [Tuebingen Univ. (Germany). Inst. of Brain Research; Tuebingen Univ. (Germany). General Internal Medicine

    2007-05-15

    Background: Little is known about the immediate effects of whole-brain {gamma}-irradiation. The authors hypothesize that Egr1 as an immediate early gene and microglia both participate in early reactions. Material and Methods: Both, expression of Egr1 and cellular distribution were studied in a temporal sequence in different brain regions of rats subjected to irradiation with 10 Gy. Brain tissue was examined using immunohistochemistry, real-time RT-PCR (reverse transcription-polymerase chain reaction), and Western blotting. Results: Astroglia and oligodendroglia showed increased Egr1 immunoreactivity within the first hours following irradiation. This was accompanied by a strong peak in CD68 immunoreactivity histologically attributable to activated microglia. A high constitutive expression of Egr1 protein in the nuclei of activated neurons was reduced following irradiation and RT-PCR demonstrated significantly reduced levels of egr1-lv as a neuronal activity-related mRNA variant. Conclusion: The induction of Egr1 in glial cells, as well as the activation of microglia take place earlier than histological changes reported so far. The authors revealed a temporal sequence of reactions that point toward the initiation of an immediate inflammatory response including reduced neuronal activity. (orig.)

  18. The effect of hypothermia on the expression of TIMP-3 after traumatic brain injury in rats.

    Science.gov (United States)

    Jia, Feng; Mao, Qing; Liang, Yu-Min; Jiang, Ji-Yao

    2014-02-15

    Here we investigate the effect of hypothermia on the expression of apoptosis-regulating protein TIMP-3 after fluid percussion traumatic brain injury (TBI) in rats. We began with 210 adult male Sprague-Dawley rats and randomly assigned them to three groups: TBI with hypothermia treatment (32°C), TBI with normothermia (37°C), and sham-injured controls. TBI was induced by a fluid percussion TBI device. Mild hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. The rats were killed at 4, 6, 12, 24, 48, and 72 h and 1 week after TBI. The mRNA and protein level of TIMP-3 in both the injured and uninjured hemispheres of the brains from each group were measured using RT-PCR and Western blotting. In the normothermic group, TIMP-3 levels in both the injured and uninjured hemispheres were significantly increased after TBI compared with those of sham-injured animals (p percussion brain injury significantly upregulates TIMP-3 expression, and that this increase may be suppressed by hypothermia treatment. PMID:23256480

  19. Changes in Rat Brain MicroRNA Expression Profiles Following Sevoflurane and Propofol Anesthesia

    Directory of Open Access Journals (Sweden)

    Yu Lu

    2015-01-01

    Full Text Available Background: Sevoflurane and propofol are widely used anesthetics for surgery. Studies on the mechanisms of general anesthesia have focused on changes in protein expression properties and membrane lipid. MicroRNAs (miRNAs regulate neural function by altering protein expression. We hypothesize that sevoflurane and propofol affect miRNA expression profiles in the brain, expect to understand the mechanism of anesthetic agents. Methods: Rats were randomly assigned to a 2% sevoflurane group, 600 μg·kg − 1·min − 1 propofol group, and a control group without anesthesia (n = 4, respectively. Treatment group was under anesthesia for 6 h, and all rats breathed spontaneously with continuous monitoring of respiration and blood gases. Changes in rat cortex miRNA expression profiles were analyzed by miRNA microarrays and validated by quantitative real-time polymerase chain reaction (qRT-PCR. Differential expression of miRNA using qRT-PCR among the control, sevoflurane, and propofol groups were compared using one-way analysis of variance (ANOVA. Results: Of 677 preloaded rat miRNAs, the microarray detected the expression of 277 miRNAs in rat cortex (40.9%, of which 9 were regulated by propofol and (or sevoflurane. Expression levels of three miRNAs (rno-miR-339-3p, rno-miR-448, rno-miR-466b-1FNx01 were significantly increased following sevoflurane and six (rno-miR-339-3p, rno-miR-347, rno-miR-378FNx01, rno-miR-412FNx01, rno-miR-702-3p, and rno-miR-7a-2FNx01 following propofol. Three miRNAs (rno-miR-466b-1FNx01, rno-miR-3584-5p and rno-miR-702-3p were differentially expressed by the two anesthetic treatment groups. Conclusions: Sevoflurane and propofol anesthesia induced distinct changes in brain miRNA expression patterns, suggesting differential regulation of protein expression. Determining the targets of these differentially expressed miRNAs may help reveal both the common and agent-specific actions of anesthetics on neurological and physiological

  20. A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure

    OpenAIRE

    Enoch, Mary-Anne; Baghal, Basel; Yuan, Qiaoping; Goldman, David

    2013-01-01

    Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABAA gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions...

  1. Rice From Mercury Contaminated Areas in Guizhou Province Induces c-jun Expression in Rat Brain

    Institute of Scientific and Technical Information of China (English)

    JIN-PING CHENG; WEN-HUA WANG; LI-YA QU; JIN-PING JIA; MIN ZHENG; XIU-LING JI; TAO YUAN

    2005-01-01

    Objective Mercury (Hg), as one of the priority pollutants and also a hot topic of frontier environmental research in many countries, has been paid higher attention in the world since the middle of the last century. Guizhou Province (at N24°30′-29°13′, E103°1′-109°30′, 1 100 m above the sea level, with subtropical humid climate) in southwest China is an important mercury production center. It has been found that the mercury content in most media of aquatics, soil, atmosphere and in biomass of corns, plants and animals, is higher than the national standard.The present study aims to explore the influence of mercury pollution on the health of local citizens. Methods The effect of rice from two mercury polluted experimental plots of Guizhou Province on the expression of c-jun mRNA in rat brain and c-jun protein in cortex, hippocampus and ependyma was observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. Results The results showed that the mercury polluted rice induced expression of c-jun mRNA and its protein significantly. Selenium can reduce Hg uptake, an antagonism between selenium and mercury on the expression of c-jun mRNA and c-jun protein. Conclusion c-jun participates in the toxicity process of brain injury by mercury polluted rice, the expression of c- jun mRNA in brain, and c-jun protein in rat cortex and hippocampus can predict neurotoxicity of mercury polluted rice. People should be advised to be cautious in eating any kind of Hg-polluted foods. To reveal the relationship between c-jun induction and apoptosis, further examinations are required.

  2. Seasonal and regional differences in gene expression in the brain of a hibernating mammal.

    Directory of Open Access Journals (Sweden)

    Christine Schwartz

    Full Text Available Mammalian hibernation presents a unique opportunity to study naturally occurring neuroprotection. Hibernating ground squirrels undergo rapid and extreme physiological changes in body temperature, oxygen consumption, and heart rate without suffering neurological damage from ischemia and reperfusion injury. Different brain regions show markedly different activity during the torpor/arousal cycle: the cerebral cortex shows activity only during the periodic returns to normothermia, while the hypothalamus is active over the entire temperature range. Therefore, region-specific neuroprotective strategies must exist to permit this compartmentalized spectrum of activity. In this study, we use the Illumina HiSeq platform to compare the transcriptomes of these two brain regions at four collection points across the hibernation season: April Active, October Active, Torpor, and IBA. In the cerebral cortex, 1,085 genes were found to be differentially expressed across collection points, while 1,063 genes were differentially expressed in the hypothalamus. Comparison of these transcripts indicates that the cerebral cortex and hypothalamus implement very different strategies during hibernation, showing less than 20% of these differentially expressed genes in common. The cerebral cortex transcriptome shows evidence of remodeling and plasticity during hibernation, including transcripts for the presynaptic cytomatrix proteins bassoon and piccolo, and extracellular matrix components, including laminins and collagens. Conversely, the hypothalamic transcriptome displays upregulation of transcripts involved in damage response signaling and protein turnover during hibernation, including the DNA damage repair gene RAD50 and ubiquitin E3 ligases UBR1 and UBR5. Additionally, the hypothalamus transcriptome also provides evidence of potential mechanisms underlying the hibernation phenotype, including feeding and satiety signaling, seasonal timing mechanisms, and fuel

  3. PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption.

    Science.gov (United States)

    Ferguson, Laura B; Most, Dana; Blednov, Yuri A; Harris, R Adron

    2014-11-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior. PMID:25036611

  4. Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

    OpenAIRE

    Tal, M.; Schneider, D L; Thorens, B.; Lodish, H F

    1990-01-01

    The "erythroid/brain" glucose transporter (GT) isoform is expressed only in a subset of hepatocytes, those forming the first row around the terminal hepatic venules, while the "liver" GT is expressed in all hepatocytes. After 3 d of starvation, a three- to fourfold elevation of expression of the erythroid/brain GT mRNA and protein is detected in the liver as a whole; this correlates with the expression of this GT in more hepatocytes, those forming the first three to four rows around the hepat...

  5. Polychlorinated biphenyls alter expression of alpha-synuclein, synaptophysin and parkin in the rat brain

    DEFF Research Database (Denmark)

    Malkiewicz, Katarzyna; Mohammed, Roma; Folkesson, Ronnie;

    2006-01-01

    Polychlorinated Biphenyls (PCBs)-induced changes in synaptic transmission are one of the effects of their neurotoxicity but the mechanism remains unknown. We assessed the in vivo effects of the PCBs mixture, Aroclor 1254 on the expression of neuronal proteins that are involved in the synaptic...... function and/or are associated with neurodegeneration. Wistar rats were treated orally with repeated doses of Aroclor 1254 and the levels of soluble alpha-synuclein, parkin, synaptophysin and amyloid precursor protein (APP) in the brain were determined by Western blotting. The results showed that Aroclor...... did not cause changes in the expression and processing of APP but at a dose 100 microg/g/day repeated for 6 days caused a decrease in the expression of alpha-synuclein in the cerebellum, cortex, hippocampus and hypothalamus of the animals sacrificed 2 days after treatment. The decrease in alpha...

  6. Effects of different endocrine disruptor (EDC) mixtures on gene expression in neonatal rat brain regions

    DEFF Research Database (Denmark)

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver; Boberg, Julie; Christiansen, Sofie; Hass, Ulla; Kortenkamp, Andreas; Schlumpf, Margret

    EDC mixtures on gene expression in developing brain. Amix (8 anti-androgenic chemicals), Emix (4 estrogenic chemicals) and Tmix (Amix + Emix + paracetamol recently identified as anti-androgenic) were administered by oral gavage to rat dams from gestational day 7 until weaning, at doses corresponding...... time RT PCR of selected mRNA species in MPO and ventromedial hypothalamus (VMH) of all dose groups. Microarray analyses revealed mixture- and sex-specific effects on gene expression patterns. The majority of genes affected by an individual mixture was selective for that mixture. Real time RT PCR of...... individual mRNAs demonstrated treatment- and sex-dependent differences between MPO and VMH. Effects were dose-dependent. Prominent are effects on the expression of genes involved in excitatory glutamatergic synapse formation and function. These data indicate that effects of complex EDC mixtures on developing...

  7. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten;

    2011-01-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor....... Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression in...... tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p <0.05). The capillary length in the meningiomas was...

  8. Age-related decreased inhibitory versus excitatory gene expression in the adult autistic brain

    Directory of Open Access Journals (Sweden)

    Louie Nathan van de Lagemaat

    2014-12-01

    Full Text Available Autism spectrum disorders (ASDs are neurodevelopmental disorders characterised by impaired social interaction and communication, and restricted behaviour and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesised to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an ageing phenomenon in ASD rather than its underlying cause.

  9. The Effects of Bee Venom on iNOS, TNF-α and NF-kB in RAW 264.7 Cells

    Directory of Open Access Journals (Sweden)

    Goon-Joong Kim

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate the effects of Bee Venom on the lipopolysaccharide(LPS, sodium nitroprusside(SNP, hydrogen peroxide(H2O2-induced expression inducilble nitric oxide synthetase(iNOS, tumor necrosis factor-α(TNF-α and nuclear factor kappa B(NF-kB in RAW 264.7 cells, a murine macrophage cell line. Methods : The expressions of expression iNOS and TNF-α were determined by western blotting with corresponding antibodies. The expressions of expression NF-kB was assayed by EMSA method. Results : 1. The 0.5, 1 and 5 ㎍/㎖ of bee venom on LPS-induced expression of iNOS, the 5 ㎍/㎖ of bee venom on SNP-induced expression of iNOS and the 1 ㎍/㎖ of bee venom on H2O2-induced expression of iNOS compared with control were inhibited significantly. 2. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited significantly LPS and H2O2-induced expression of TNF-α compared with control, respectively. The 0.5 ㎍/㎖ of bee venom increased significantly SNP-induced expression of TNF-α compared with control. 3. The 5 ㎍/㎖ of bee venom on LPS-induced expression of NF-kB, the 0.5 ㎍/㎖ of bee venom on SNP-induced expression of NF-kB and the 0.5, 5 ㎍/㎖ of bee venom on H2O2-induced expression of NF-kB were inhibited significantly compared with control, respectively.

  10. Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain.

    Science.gov (United States)

    Saganich, M J; Machado, E; Rudy, B

    2001-07-01

    The members of the three subfamilies (eag, erg, and elk) of the ether-a-go-go (EAG) family of potassium channel pore-forming subunits express currents that, like the M-current (I(M)), could have considerable influence on the subthreshold properties of neuronal membranes, and hence the control of excitability. A nonradioactive in situ hybridization (NR-ISH) study of the distribution of the transcripts encoding the eight known EAG family subunits in rat brain was performed to identify neuronal populations in which the physiological roles of EAG channels could be studied. These distributions were compared with those of the mRNAs encoding the components of the classical M-current (Kcnq2 and Kcnq3). NR-ISH was combined with immunohistochemistry to specific neuronal markers to help identify expressing neurons. The results show that each EAG subunit has a specific pattern of expression in rat brain. EAG and Kcnq transcripts are prominent in several types of excitatory neurons in the cortex and hippocampus; however, only one of these channel components (erg1) was consistently expressed in inhibitory interneurons in these areas. Some neuronal populations express more than one product of the same subfamily, suggesting that the subunits may form heteromeric channels in these neurons. Many neurons expressed multiple EAG family and Kcnq transcripts, such as CA1 pyramidal neurons, which contained Kcnq2, Kcnq3, eag1, erg1, erg3, elk2, and elk3. This indicates that the subthreshold current in many neurons may be complex, containing different components mediated by a number of channels with distinct properties and neuromodulatory responses. PMID:11425889

  11. Prion disease induced alterations in gene expression in spleen and brain prior to clinical symptoms

    Directory of Open Access Journals (Sweden)

    Hyeon O Kim

    2008-09-01

    Full Text Available Hyeon O Kim1, Greg P Snyder1, Tyler M Blazey1, Richard E Race2, Bruce Chesebro2, Pamela J Skinner11Department of Veterinary and Biomedical Sciences, University of Minnesota, USA; 2NIH Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana, USAAbstract: Prion diseases are fatal neurodegenerative disorders that affect animals and humans. There is a need to gain understanding of prion disease pathogenesis and to develop diagnostic assays to detect prion diseases prior to the onset of clinical symptoms. The goal of this study was to identify genes that show altered expression early in the disease process in the spleen and brain of prion disease-infected mice. Using Affymetrix microarrays, we identified 67 genes that showed increased expression in the brains of prion disease-infected mice prior to the onset of clinical symptoms. These genes function in many cellular processes including immunity, the endosome/lysosome system, hormone activity, and the cytoskeleton. We confirmed a subset of these gene expression alterations using other methods and determined the time course in which these changes occur. We also identified 14 genes showing altered expression prior to the onset of clinical symptoms in spleens of prion disease infected mice. Interestingly, four genes, Atp1b1, Gh, Anp32a, and Grn, were altered at the very early time of 46 days post-infection. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as surrogate markers for the early detection and diagnosis of prion disease.Keywords: prion disease, microarrays, gene expression

  12. Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine.

    Science.gov (United States)

    Enoch, M-A; Rosser, A A; Zhou, Z; Mash, D C; Yuan, Q; Goldman, D

    2014-11-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from 'BrainSpan' was obtained across 16 brain regions from nine control adults. We also generated RNA-Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic (AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up-regulated in both alcoholics and cocaine addicts (FDR corrected P = 0.008). Alcoholics showed up-regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 (GluR7) and GRM4 (mGluR4). Expression of both GRM3 (mGluR3) and GRIN2D (GluN2D) was up-regulated in alcoholics and down-regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up-regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit. PMID:25262781

  13. Atmospheric neutrino flux at INO, South Pole and Pyhaesalmi

    Energy Technology Data Exchange (ETDEWEB)

    Sajjad Athar, M., E-mail: sajathar@gmail.com [Department of Physics, Aligarh Muslim University, Aligarh-202002 (India); Honda, M., E-mail: mhonda@icrr.u-tokyo.ac.jp [Institute for Cosmic Ray Research, the University of Tokyo, 5-1-5 Kashiwa-no-ha, Kashiwa, Chiba 277-8582 (Japan); Kajita, T., E-mail: kajita@icrr.u-tokyo.ac.jp [Kavli Institute for the Physics and the Mathematics of the Universe, the University of Tokyo, 5-1-5 Kashiwa-no-ha, Kashiwa, Chiba 277-8582 (Japan); Institute for Cosmic Ray Research, the University of Tokyo, 5-1-5 Kashiwa-no-ha, Kashiwa, Chiba 277-8582 (Japan); Kasahara, K., E-mail: kasahara@icrc.u-tokyo.ac.jp [Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo Shinjuku-ku, Tokyo, 169-8555 (Japan); Midorikawa, S., E-mail: midori@aomori-u.ac.jp [Faculty of Software and Information Technology, Aomori University, Aomori, 030-0943 (Japan)

    2013-01-29

    We present the calculation of the atmospheric neutrino fluxes for the neutrino experiments proposed at INO, South Pole and Pyhaesalmi. Neutrino fluxes have been obtained using ATMNC, a simulation code for cosmic ray in the atmosphere. Even using the same primary flux model and the interaction model, the calculated atmospheric neutrino fluxes are different for the different sites due to the geomagnetic field. The prediction of these fluxes in the present Letter would be quite useful in the experimental analysis.

  14. Cloning of a Gene Whose Expression is Increased in Scrapie and in Senile Plaques in Human Brain

    Science.gov (United States)

    Wietgrefe, S.; Zupancic, M.; Haase, A.; Chesebro, B.; Race, R.; Frey, W.; Rustan, T.; Friedman, R. L.

    1985-12-01

    A complementary DNA library was constructed from messenger RNA's extracted from the brains of mice infected with the scrapie agent. The library was differentially screened with the objectives of finding clones that might be used as markers of infection and finding clones of genes whose increased expression might be correlated with the pathological changes common to scrapie and Alzheimer's disease. A gene was identified whose expression is increased in scrapie. The complementary DNA corresponding to this gene hybridized preferentially and focally to cells in the brains of scrapie-infected animals. The cloned DNA also hybridized to the neuritic plaques found with increased frequency in brains of patients with Alzheimer's disease.

  15. GENDER DIFFERENCES IN BRAIN SUSCEPTIBILITY TO OXIDATIVE STRESS ARE MEDIATED BY LEVELS OF PARAOXONASE-2 (PON2) EXPRESSION

    OpenAIRE

    Giordano, G.; Tait, L.; Furlong, C E; Cole, T B; Kavanagh, T J; Costa, L.G.

    2013-01-01

    Paraoxonase 2 (PON2), a member of a gene family that also includes PON1 and PON3, is expressed in most tissues, including the brain. In mouse brain, PON2 levels are highest in dopaminergic areas (e.g. striatum), and are higher in astrocytes than in neurons. PON2 is primarily located in mitochondria and exerts a potent antioxidant effect, protecting mouse CNS cells against oxidative stress. The aim of this study was to characterize PON2 expression and functions in the brains of male and female...

  16. EXPRESSING HUMAN MATURED BRAIN-DERIVED NEUROTROPHIC FACTOR GENE IN E. Coli AND DETERMINING ITS BIOACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Expressing the human matured brain-derived neurotrophic factor (mBDNF) gene in E.Coli and determining its bioactivity. Methods The resulting gene of mBDNF was subcloned into the EcoRI-BamHI site of the expression vector plasmid pBV220. The ligation products were used to transform the competent E. Coli DH5α. The proteins of mBDNF were experessed by temperature inducing. The expression products were dealed with solubilizing inclusion bodies and refolding protein. It was introduced into the embryonic chicken DRG to test whether the expressed mBDNF is a biologically active protein. Results The recombinant plasmid pBV/mBDNF was successfully constructed. By temperature inducing,under the control of the bacteriophage λ PL promoter, the experessed mBDNF protein was a 14Kd non-fusion protein,which existed in E. Coli as inclusion bodies. The size of expressed mBDNF is identical to the prediction. Bioactivity of the products was proved that it could support the cell survival and neurite growth in the primary cultures of embryonic 8-day-old chicken DRG neurons as compared to control.Conclusion The mBDNF gene can be expressed bioactively in E. Coli.

  17. Cell surface modulation of gene expression in brain cells by down regulation of glucocorticoid receptors

    Energy Technology Data Exchange (ETDEWEB)

    McGinnis, J.F.; de Vellis, J.

    1981-02-01

    The concentration of glycerol-3-phosphate dehydrogenase (GPDH; sn-glycerol-3-phosphate:NAD/sup +/ 2-oxidoreductase, EC 1.1.1.8) had previously been determined to be regulated by glucocorticoids in rat brain cells in vivo and in cell culture. We now demonstrate that concanavalin A (Con A) can inhibit the induction of GPDH in a dose-dependent manner in C6 rat glioma cells and in primary cultures of rat brain oligodendrocytes. The inhibition specifically prevents the appearance of new molecules of GPDH, although Con A does not significantly inhibit protein synthesis in these cells, nor does it affect the activity of another solube enzyme, lactate dehydrogenase. The ability to block enzyme induction is not limited to Con A, because other lectins also inhibit induction. The molecular mechanism by which Con A inhibits GPDH induction appears to be by the down regulation of the cytoplasmic glucocorticoid receptors, because exposure to Con A results in the loss of more than 90% of the receptor activity. Con A does not inhibit the receptor assay and no direct interaction between the receptor and Con A could be demonstrated. This down regulation is not tumor cell specific and appears to be a general phenomenon, because it occurs in normal oligodendrocytes and even in normal astrocytes (a cell type in which the gene for GPDH is not expressed). The down regulation of glucocorticoid receptors in normal brain cells suggests two important corollaries. First, it demonstrates the existence of a rate-limiting step controlling the glucocorticoid-dependent gene expression in brain cells and possibly represents a regulatory site common to all glucocorticoid target cells. Second, it suggests that the response to glucocorticoids of oligodendrocytes and astrocytes can be regulated in vivo by cell surface contact with endogenous lectins, neighboring cells, or both.

  18. Search for Magnetic Monopole using ICAL at INO

    CERN Document Server

    Dash, N; Majumder, G

    2014-01-01

    Sub-relativistic magnetic monopoles are predicted from the GUT era by theory. To date there have been no confirmed observations of such exotic particles. The Iron CALorimeter (ICAL) at India-based Neutrino Observatory (INO) aims to measure the neutrino oscillation parameters precisely. As it is a tracking detector there is also the possibility of detecting magnetic monopoles in the sub-relativistic region. Using ICAL the magnetic monopole event is characterised by the large time intervals of upto 30 microsec between the signals in successive layers of the active detectors. The aim of this study is to identify the sensitivity of ICAL for a particle carrying magnetic charge in the mass range from 10^{5} to 10^{17} GeV with beta ranging from 10^{-5} to 9 x 10^{-1} for ICAL at INO. A similar study has also been carried out for the ICAL prototype which will be placed overground. Due to the rock cover of approximately 1.3 km, ICAL at INO will not be able to place bounds on the flux of the lower mass magnetic monopo...

  19. The Chinese herbal formula Tongluo Jiunao promotes expression of brain-derived neurotrophic factor/tropomyosin-related kinase B pathways in a rat model of ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Peiman Alesheikh; Yangyang Yan; Huiling Tang; Pengtao Li; Wei Zhang; Yanshu Pan; Arezou Mashoufi; Liyun Zhao; Runjun Wang; Bo Di

    2011-01-01

    The neurotrophin-Trk receptor pathway is an intrinsic pathway to relieve damage to the central nervous system. The present study observed the effects of Tongluo Jiunao (TLJN), which comprises Panax Notoginseng and Gardenia Jasminoides, on expression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) in a rat model of focal cerebral ischemic injury. Xue Sai Tong (XST), comprising Panax Notoginseng, served as the positive control. Mechanisms of neuroprotection were analyzed following TLJN injection. Following establishment of the middle cerebral artery occlusion models, TLJN and XST were intraperitoneally injected, and 2, 3, 5-triphenyltetrazolium chloride staining results revealed that TLJN injection reduced infarct volume, suggesting that TLJN exerted a neuroprotective effect. Enzyme-linked immunosorbent assay results showed that TLJN elevated BDNF and growth associated protein-43 expression in ischemic brain tissues, as well as serum BDNF levels. Reverse-transcription polymerase chain reaction and western blot results showed that TLJN injection did not affect TrkB expression in the ischemic brain tissues of rats. These results suggested that TLJN injection reduced damage to ischemic brain tissues and increased BDNF expression. In addition, TLJN injection resulted in better promoting effects on neurotrophic factor expression compared with XST.

  20. Seizure-related 6,a brain-specific expression gene,is highly expressed in the human cerebellum

    Institute of Scientific and Technical Information of China (English)

    Jianming Jiang; Long Yu; Yangtai Guan; Zhiliang Yu; Xinghua Huang; Xiaosong Chen; Lisha Tang; Xianning Zhang

    2010-01-01

    Epilepsy is a complex,Mendelian disease,and most cases are sporadic.Genomic comparisons of tissue from identified monogenic epilepsies with multigenic and acquired syndromes could ultimately reveal crucial molecular neuropathology for an epileptic phenotype.In the present study,a novel gene,human seizure-related(hSEZ)-6,was isolated from a human brain cDNA library.hSEZ-6 comprises 17 exons and spans a region of at least 55.6 kb,which was localized to 17q12 by radiation hybridization,hSEZ-6 exhibits two isoform types,hSEZ-6A and hSEZ-6B,which encode996 and 995 amino acids,respectively.The two putative hSEZ-6 proteins contain similar motifs and share 82% and 84% identity with mouse SEZ-6A protein,whose expression level increased in mouse cerebral cortex-derived cells treated with a convulsant drug,pentylentetrazole.Northern blot analysis demonstrated that hSEZ-6 is expressed highly in the cerebellum and in nucleus of the extrapyramidal system,such as the caudate nucleus and putamen.Reverse transcription polymerase chain reaction revealed that hSEZ-6 is expressed in neurons rather than gliocytes,which suggests that hSEZ-6 is a seizure-related gene.

  1. Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.

    Directory of Open Access Journals (Sweden)

    J Raphael Gibbs

    2010-05-01

    Full Text Available A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We present a set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals (600 samples total. We find an abundance of genetic cis regulation of mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation across the genome. We show peak enrichment for cis expression QTLs to be approximately 68,000 bp away from individual transcription start sites; however, the peak enrichment for cis CpG methylation QTLs is located much closer, only 45 bp from the CpG site in question. We observe that the largest magnitude quantitative trait loci occur across distinct brain tissues. Our analyses reveal that CpG methylation quantitative trait loci are more likely to occur for CpG sites outside of islands. Lastly, we show that while we can observe individual QTLs that appear to affect both the level of a transcript and a physically close CpG methylation site, these are quite rare. We believe these data, which we have made publicly available, will provide a critical step toward understanding the biological effects of genetic variation.

  2. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Veronica H Ryan

    Full Text Available The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades.AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism.Expression patterns were split into Development (0 to 20 years and Aging (21 to 78 years intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2, cyclooxygenases (COX-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA and PTGS2 (COX-2 genes at 1q25, highly inter-correlated genes were at distant chromosomal loci.Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  3. Expression of innate immune complement regulators on brain epithelial cells during human bacterial meningitis

    Directory of Open Access Journals (Sweden)

    Gasque Philippe

    2006-09-01

    Full Text Available Abstract Background In meningitis, the cerebrospinal fluid contains high levels of innate immune molecules (e.g. complement which are essential to ward off the infectious challenge and to promote the infiltration of phagocytes (neutrophils, monocytes. However, epithelial cells of either the ependymal layer, one of the established niche for adult neural stem cells, or of the choroid plexus may be extremely vulnerable to bystander attack by cytotoxic and cytolytic complement components. Methods In this study, we assessed the capacity of brain epithelial cells to express membrane-bound complement regulators (ie, CD35, CD46, CD55 and CD59 in vitro and in situ by immunostaining of control and meningitis human brain tissue sections. Results Double immunofluorescence experiments for ependymal cell markers (GFAP, S100, ZO-1, E-cadherin and complement regulators indicated that the human ependymal cell line model was strongly positive for CD55, CD59 compared to weak stainings for CD46 and CD35. In tissues, we found that CD55 was weakly expressed in control choroid plexus and ependyma but was abundantly expressed in meningitis. Anti-CD59 stained both epithelia in apical location while increased CD59 staining was solely demonstrated in inflamed choroid plexus. CD46 and CD35 were not detected in control tissue sections. Conversely, in meningitis, the ependyma, subependyma and choroid plexus epithelia were strongly stained for CD46 and CD35. Conclusion This study delineates for the first time the capacity of brain ependymal and epithelial cells to respond to and possibly sustain the innate complement-mediated inflammatory insult.

  4. Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain.

    Science.gov (United States)

    Farsetti, A; Mitsuhashi, T; Desvergne, B; Robbins, J; Nikodem, V M

    1991-12-01

    Regulation of myelin basic protein (MBP) gene expression by thyroid hormone has been investigated in rodent brain. Quantitation of the 4 major alternatively spliced transcripts by RNase protection assay showed that the individual mRNAs, corresponding to MBP isoforms 21.5, 18.5, 17, and 14 kDa, were decreased from 2- to 17-fold at all ages studied (4-60 days) in hypothyroid animals when compared to euthyroid, but the timing of onset of expression was not altered. MBP mRNA was also reduced in young adult rats thyroidectomized at the age of 5-6 weeks and was restored to normal by thyroxine administration. Nuclear run-off assays showed that the rate of MBP gene transcription is dependent on thyroid state. Co-transfection of MBP (-256/+1)-chloramphenicol acetyltransferase chimeric gene with a plasmid expressing thyroid hormone receptor alpha, and in the presence of 3,5,3'-triiodothyronine, into NIH3T3 or NG108-15, increased chloramphenicol acetyltransferase expression 4-fold. Using a footprinting technique and Spodoptera frugiperda 9 (Sf9) nuclear extract infected with baculovirus expressing TR alpha, we have identified a single DNA-binding site (-186/-163) for the receptor. A part of this region contains the AGGACA sequence found in thyroid hormone-responsive elements of other 3,5,3'-triiodothyronine-regulated genes. Our finding of a specific hormone-receptor interaction with the MBP promoter region is the first direct demonstration of a thyroid hormone-responsive element in a brain-specific gene. PMID:1720778

  5. Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences.

    Science.gov (United States)

    Stamou, Marianna; Wu, Xianai; Kania-Korwel, Izabela; Lehmler, Hans-Joachim; Lein, Pamela J

    2014-02-01

    Cytochrome P450 (P450) enzymes play a critical role in the activation and detoxication of many neurotoxic chemicals. Although research has largely focused on P450-mediated metabolism in the liver, emerging evidence suggests that brain P450s influence neurotoxicity by modulating local metabolite levels. As a first step toward better understanding the relative role of brain P450s in determining neurotoxic outcome, we characterized mRNA expression of specific P450 isoforms in the rodent brain. Adult mice (male and female) and rats (male) were treated with vehicle, phenobarbital, or dexamethasone. Transcripts for CYP2B, CYP3A, CYP1A2, and the orphan CYP4X1 and CYP2S1 were quantified in the liver, hippocampus, cortex, and cerebellum by quantitative (real-time) polymerase chain reaction. These P450s were all detected in the liver with the exception of CYP4X1, which was detected in rat but not mouse liver. P450 expression profiles in the brain varied regionally. With the exception of the hippocampus, there were no sex differences in regional brain P450 expression profiles in mice; however, there were marked species differences. In the liver, phenobarbital induced CYP2B expression in both species. Dexamethasone induced hepatic CYP2B and CYP3A in mice but not rats. In contrast, brain P450s did not respond to these classic hepatic P450 inducers. Our findings demonstrate that P450 mRNA expression in the brain varies by region, regional brain P450 profiles vary between species, and their induction varies from that of hepatic P450s. These novel data will be useful for designing mechanistic studies to examine the relative role of P450-mediated brain metabolism in neurotoxicity. PMID:24255117

  6. Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration

    Science.gov (United States)

    Gibbs, Holly C.; Dodson, Colin R.; Bai, Yuqiang; Lekven, Arne C.; Yeh, Alvin T.

    2014-12-01

    During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

  7. Reduction of photo bleaching and long term archiving of chemically cleared GFP-expressing mouse brains.

    Directory of Open Access Journals (Sweden)

    Klaus Becker

    Full Text Available Tissue clearing allows microscopy of large specimens as whole mouse brains or embryos. However, lipophilic tissue clearing agents as dibenzyl ether limit storage time of GFP-expressing samples to several days and do not prevent them from photobleaching during microscopy. To preserve GFP fluorescence, we developed a transparent solid resin formulation, which maintains the specimens' transparency and provides a constant signal to noise ratio even after hours of continuous laser irradiation. If required, high-power illumination or long exposure times can be applied with virtually no loss in signal quality and samples can be archived for years.

  8. Reduction of photo bleaching and long term archiving of chemically cleared GFP-expressing mouse brains.

    Science.gov (United States)

    Becker, Klaus; Hahn, Christian Markus; Saghafi, Saiedeh; Jährling, Nina; Wanis, Martina; Dodt, Hans-Ulrich

    2014-01-01

    Tissue clearing allows microscopy of large specimens as whole mouse brains or embryos. However, lipophilic tissue clearing agents as dibenzyl ether limit storage time of GFP-expressing samples to several days and do not prevent them from photobleaching during microscopy. To preserve GFP fluorescence, we developed a transparent solid resin formulation, which maintains the specimens' transparency and provides a constant signal to noise ratio even after hours of continuous laser irradiation. If required, high-power illumination or long exposure times can be applied with virtually no loss in signal quality and samples can be archived for years. PMID:25463047

  9. INFLUENCE OF MALIGNIZATIONS LEVEL OF ASTROCYTIC HUMAN BRAIN TUMOR ON THE EXPRESSION OF CONNEXIN-43

    Directory of Open Access Journals (Sweden)

    Grankina A. O.

    2013-11-01

    Full Text Available Study was performed on 12 samples of astrocytic human brain tumors, which differ by the level of malignancy and histological indications. The study was conducted with the method of immunohistochemistry using a commercially available antibody anti-connexin-43 (Cx 43, a prior test of which was carried out on myocardium tissue of rats (positive control. The study showed that with the increasing of malignant level of astrocytomas, there was marked the decreased level of connexin-43 expression of, which is apparently to be associated with the destruction of intercellular gap junctions in tumor tissue

  10. Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation

    Directory of Open Access Journals (Sweden)

    Breilid Harald

    2007-04-01

    Full Text Available Abstract Background The mammalian brain is divided into distinct regions with structural and neurophysiological differences. As a result, gene expression is likely to vary between regions in relation to their cellular composition and neuronal function. In order to improve our knowledge and understanding of regional patterns of gene expression in the CNS, we have generated a global map of gene expression in selected regions of the adult rat brain (frontomedial-, temporal- and occipital cortex, hippocampus, striatum and cerebellum; both right and left sides as well as in three major non-neural tissues (spleen, liver and kidney using the Applied Biosystems Rat Genome Survey Microarray. Results By unsupervised hierarchical clustering, we found that the transcriptome within a region was highly conserved among individual rats and that there were no systematic differences between the two hemispheres (right versus left side. Further, we identified distinct sets of genes showing significant regional enrichment. Functional annotation of each of these gene sets clearly reflected several important physiological features of the region in question, including synaptic transmission within the cortex, neurogenesis in hippocampus and G-protein-mediated signalling in striatum. In addition, we were able to reveal potentially new regional features, such as mRNA transcription- and neurogenesis-annotated activities in cerebellum and differential use of glutamate signalling between regions. Finally, we determined a set of 'CNS-signature' genes that uncover characteristics of several common neuronal processes in the CNS, with marked over-representation of specific features of synaptic transmission, ion transport and cell communication, as well as numerous novel unclassified genes. Conclusion We have generated a global map of gene expression in the rat brain and used this to determine functional processes and pathways that have a regional preference or ubiquitous

  11. Metallothionein-I overexpression alters brain inflammation and stimulates brain repair in transgenic mice with astrocyte-targeted interleukin-6 expression

    DEFF Research Database (Denmark)

    Penkowa, Milena; Camats, Jordi; Giralt, Mercedes;

    2003-01-01

    injury, such as a cryolesion, demonstrate a neuroprotective role of IL-6. Thus, the GFAP-IL-6 mice showed faster tissue repair and decreased oxidative stress and apoptosis compared with control litter-mate mice. The neuroprotective factors metallothionein-I+II (MT-I+II) were upregulated by the cryolesion...... the inflammatory response, decreased oxidative stress and apoptosis significantly, and increased brain tissue repair in comparison with either GFAP-IL-6 or control litter-mate mice. Overall, the results demonstrate that brain MT-I+II proteins are fundamental neuroprotective factors.......Transgenic expression of IL-6 in the CNS under the control of the GFAP gene promoter, glial fibrillary acidic protein-interleukin-6 (GFAP-IL-6) mice, raises an inflammatory response and causes significant brain damage. However, the results obtained in the GFAP-IL-6 mice after a traumatic brain...

  12. Personality Trait and Facial Expression Filter-Based Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Seongah Chin

    2013-02-01

    Full Text Available In this paper, we present technical approaches that bridge the gap in the research related to the use of brain‐computer interfaces for entertainment and facial expressions. Such facial expressions that reflect an individual’s personal traits can be used to better realize artificial facial expressions in a gaming environment based on a brain‐computer interface. First, an emotion extraction filter is introduced in order to classify emotions on the basis of the users’ brain signals in real time. Next, a personality trait filter is defined to classify extrovert and introvert types, which manifest as five traits: very extrovert, extrovert, medium, introvert and very introvert. In addition, facial expressions derived from expression rates are obtained by an extrovert‐introvert fuzzy model through its defuzzification process. Finally, we confirm this validation via an analysis of the variance of the personality trait filter, a k‐fold cross validation of the emotion extraction filter, an accuracy analysis, a user study of facial synthesis and a test case game.

  13. Expression and regulation of the Fkbp5 gene in the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Sebastian H Scharf

    Full Text Available BACKGROUND: Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR. The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5. Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN and the central amygdala (CeA. Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA. CONCLUSIONS/SIGNIFICANCE: Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain.

  14. Risperidone regulates Dopamine D2-like receptors expression in rat brain in a time-dependent manner

    Directory of Open Access Journals (Sweden)

    Ni Peiyan

    2015-03-01

    Full Text Available Background and Objectives: Antipsychotics can elicit dopamine super-sensitivity by up-regulation of D2-like receptors (DRD2, DRD3, and DRD4 expression. Nevertheless, the expression profile of dopamine D2-like receptors in different brain regions and peripheral blood mononuclear cells (PBMCs, and changes following risperidone administration were still unclear. In this study, we would investigate the expression of D2-like receptors mRNA in different brain regions and the peripheral blood mononuclear cells (PBMCs in rats after 2, 6 weeks risperidone administration. Methods: The experimental rats were given risperidone (0.25mg/kg/day, i.p., and the control rats were given 0.9% NaCl. The rats were sacrificed at 0 week, 2 weeks and 6 weeks after the drug administration. Expression of the dopamine D2-like receptors was quantified by Real-time PCR method. Results: Dopamine D2-like receptors expressed in all the examined regions of rat brain. Their expression significantly increased 2weeks after risperidone administration in different brain regions. However, the changed expression of DRD2 and DRD3 turned back to the basal level 6weeks later, while the increased DRD4 expression remained in left parietal cortex. Meanwhile, DRD2 and DRD3 but not DRD4 expressed in PBMCs, however, the risperidone could not affect their expression. Conclusions: The risperidone could change the dopamine D2-like receptors expression in a time-dependent manner in different brain regions, which might guide the clinical use in the near future.

  15. Analysis of axon tract formation in the zebrafish brain: the role of territories of gene expression and their boundaries.

    Science.gov (United States)

    Wilson, S W; Brennan, C; Macdonald, R; Brand, M; Holder, N

    1997-11-01

    Mutant analysis in the zebrafish is revealing the genes that are expressed in the early neuroepithelium and that regulate factors responsible for the guidance of commissural axons. We review work on the developing zebrafish brain illustrating the way in which territories of regulatory gene expression influence the formation and positioning of axon pathways. PMID:9321679

  16. Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain

    Directory of Open Access Journals (Sweden)

    Fredholm Merete

    2007-09-01

    Full Text Available Abstract Background The transmembrane presenilin (PSEN proteins, PSEN1 and PSEN2, have been proposed to be the catalytic components of the γ-secretase protein complex, which is an intramembranous multimeric protease involved in development, cell regulatory processes, and neurodegeneration in Alzheimer's disease. Here we describe the sequencing, chromosomal mapping, and polymorphism analysis of PSEN1 and PSEN2 in the domestic pig (Sus scrofa domesticus. Results The porcine presenilin proteins showed a high degree of homology over their entire sequences to the PSENs from mouse, bovine, and human. PSEN1 and PSEN2 transcription was examined during prenatal development of the brain stem, hippocampus, cortex, basal ganglia, and cerebellum at embryonic days 60, 80, 100, and 114, which revealed distinct temporal- and tissue-specific expression profiles. Furthermore, immunohistochemical analysis of PSEN1 and PSEN2 showed similar localization of the proteins predominantly in neuronal cells in all examined brain areas. Conclusion The data provide evidence for structural and functional conservation of PSENs in mammalian lineages, and may suggest that the high sequence similarity and colocalization of PSEN1 and PSEN2 in brain tissue reflect a certain degree of functional redundancy. The data show that pigs may provide a new animal model for detailed analysis of the developmental functions of the PSENs.

  17. Aquaporin-11: A channel protein lacking apparent transport function expressed in brain

    Directory of Open Access Journals (Sweden)

    Tsunenari Takashi

    2006-05-01

    Full Text Available Abstract Background The aquaporins are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes. Two recently described aquaporins, numbers 11 and 12, appear to be more distantly related to the other mammalian aquaporins and aquaglyceroporins. Results We report on the characterization of Aquaporin-11 (AQP11. AQP11 RNA and protein is found in multiple rat tissues, including kidney, liver, testes and brain. AQP11 has a unique distribution in brain, appearing in Purkinje cell dendrites, hippocampal neurons of CA1 and CA2, and cerebral cortical neurons. Immunofluorescent staining of Purkinje cells indicates that AQP11 is intracellular. Unlike other aquaporins, Xenopus oocytes expressing AQP11 in the plasma membrane failed to transport water, glycerol, urea, or ions. Conclusion AQP11 is functionally distinct from other proteins of the aquaporin superfamily and could represent a new aquaporin subfamily. Further studies are necessary to elucidate the role of AQP11 in the brain.

  18. Effects of different endocrine disruptor (EDC) mixtures on gene expression in neonatal rat brain regions

    DEFF Research Database (Denmark)

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver;

    2013-01-01

    Sexual brain differentiation is a potential EDC target. It depends on a combination of estrogen receptor- and androgen receptor-mediated effects in males and on estrogens in females. It is not known how these processes are affected by real-world mixtures of EDCs. We investigated the effect of three...... individual mRNAs demonstrated treatment- and sex-dependent differences between MPO and VMH. Effects were dose-dependent. Prominent are effects on the expression of genes involved in excitatory glutamatergic synapse formation and function. These data indicate that effects of complex EDC mixtures on developing...... time RT PCR of selected mRNA species in MPO and ventromedial hypothalamus (VMH) of all dose groups. Microarray analyses revealed mixture- and sex-specific effects on gene expression patterns. The majority of genes affected by an individual mixture was selective for that mixture. Real time RT PCR of...

  19. Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain

    Directory of Open Access Journals (Sweden)

    Mignot Emmanuel

    2007-05-01

    Full Text Available Abstract Background Narcolepsy causes dramatic behavioral alterations in both humans and dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli. Deficiencies in the hypocretin system are well established as the origin of the condition; both from studies in humans who lack the hypocretin ligand (HCRT and in dogs with a mutation in hypocretin receptor 2 (HCRTR2. However, little is known about molecular alterations downstream of the hypocretin signals. Results By using microarray technology we have screened the expression of 29760 genes in the brains of Doberman dogs with a heritable form of narcolepsy (homozygous for the canarc-1 [HCRTR-2-2] mutation, and their unaffected heterozygous siblings. We identified two neuropeptide precursor molecules, Tachykinin precursor 1 (TAC1 and Proenkephalin (PENK, that together with Suppressor of cytokine signaling 2 (SOCS2, showed reduced expression in narcoleptic brains. The difference was particularly pronounced in the amygdala, where mRNA levels of PENK were 6.2 fold lower in narcoleptic dogs than in heterozygous siblings, and TAC1 and SOCS2 showed 4.4 fold and 2.8 fold decrease in expression, respectively. The results obtained from microarray experiments were confirmed by real-time RT-PCR. Interestingly, it was previously shown that a single dose of amphetamine-like stimulants able to increase wakefulness in the dogs, also produce an increase in the expression of both TAC1 and PENK in mice. Conclusion These results suggest that TAC1, PENK and SOCS2 might be intimately connected with the excessive daytime sleepiness not only in dogs, but also in other species, possibly including humans.

  20. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.

    Science.gov (United States)

    Yano, S; Shinohara, H; Herbst, R S; Kuniyasu, H; Bucana, C D; Ellis, L M; Davis, D W; McConkey, D J; Fidler, I J

    2000-09-01

    We investigated the molecular mechanisms of angiogenesis in experimental brain metastasis. Cells from six different human cancer cell lines (proven to produce visceral metastasis) were injected into the internal carotid artery of nude mice. Colon carcinoma (KM12SM) and lung adenocarcinoma (PC14PE6 and PC14Br) cells produced large, fast-growing parenchymal brain metastases, whereas lung squamous cell carcinoma (H226), renal cell carcinoma (SN12PM6), and melanoma (TXM13) cells produced only a few slow-growing brain metastases. Rapidly progressing brain metastases contained many enlarged blood vessels. The expression of VEGF mRNA and protein by the tumor cells directly correlated with angiogenesis and growth of brain metastasis. Causal evidence for the essential role of VEGF in this process was provided by transfecting PC14PE6 and KM12SM cells with antisense-VEGF165 gene, which significantly decreased the incidence of brain metastasis. In contrast, transfection of H226 human lung squamous carcinoma cells with sense-VEGF121 or sense-VEGF165 neither enhanced nor inhibited formation of brain metastases. Collectively, the results indicate that VEGF expression is necessary but not sufficient for the production of brain metastasis and that the inhibition of VEGF represents an important therapeutic target. PMID:10987313

  1. Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Ying Xing; Jinting He; Weidong Yu; Lingling Hou; Jiajun Chen

    2012-01-01

    A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

  2. Identification of a novel CoA synthase isoform, which is primarily expressed in Brain

    International Nuclear Information System (INIS)

    CoA and its derivatives Acetyl-CoA and Acyl-CoA are important players in cellular metabolism and signal transduction. CoA synthase is a bifunctional enzyme which mediates the final stages of CoA biosynthesis. In previous studies, we have reported molecular cloning, biochemical characterization, and subcellular localization of CoA synthase (CoASy). Here, we describe the existence of a novel CoA synthase isoform, which is the product of alternative splicing and possesses a 29aa extension at the N-terminus. We termed it CoASy β and originally identified CoA synthase, CoASy α. The transcript specific for CoASy β was identified by electronic screening and by RT-PCR analysis of various rat tissues. The existence of this novel isoform was further confirmed by immunoblot analysis with antibodies directed to the N-terminal peptide of CoASy β. In contrast to CoASy α, which shows ubiquitous expression, CoASy β is primarily expressed in Brain. Using confocal microscopy, we demonstrated that both isoforms are localized on mitochondria. The N-terminal extension does not affect the activity of CoA synthase, but possesses a proline-rich sequence which can bring the enzyme into complexes with signalling proteins containing SH3 or WW domains. The role of this novel isoform in CoA biosynthesis, especially in Brain, requires further elucidation

  3. Daily methylphenidate and atomoxetine treatment impacts on clock gene protein expression in the mouse brain.

    Science.gov (United States)

    Baird, Alison L; Coogan, Andrew N; Kaufling, Jennifer; Barrot, Michel; Thome, Johannes

    2013-06-01

    Circadian rhythms are repeating patterns of physiological and other parameters that recur with periods of approximately 24h, and are generated by an endogenous circadian timekeeping mechanism. Such circadian rhythms, and their underlying molecular mechanisms, are known to be altered by a number of central nervous system acting pharmacological compounds, as well as becoming perturbed in a number of common psychiatric and neurological conditions. The psychostimulant methylphenidate and the non-stimulant atomoxetine are used in the pharmacotherapy of attention deficit hyperactivity disorder, a common condition in which circadian rhythms have been reported to be altered. In the present study we have examined the effects of daily methylphenidate or atomoxetine treatment across 7 days on circadian clock gene product expression across numerous brain regions in the male mouse to test the potential impact of such compounds on circadian timing. We report drug, brain region and molecular specific effects of such treatments, including alterations in expression profiles in the suprachiasmatic nucleus, the master circadian pacemaker. These results indicate that drugs used in the clinical management of attention deficit hyperactivity disorder can alter molecular factors that are believed to underpin circadian timekeeping, and such effects may be of importance in both the therapeutic and side effect profiles of such drugs. PMID:23566813

  4. Laboratory domestication changed the expression patterns of oxytocin and vasopressin in brains of rats and mice.

    Science.gov (United States)

    Ruan, Chao; Zhang, Zhibin

    2016-09-01

    The process of domestication is recognized to exert significant effects on the social behaviors of various animal species, including defensive and cognitive behaviors that are closely linked to the expression of oxytocin (OT) and vasopressin (AVP) in selected areas of the brain. However, it is still unclear whether the behavioral changes observed under domestication have resulted in differences in the neurochemical systems that regulate them. In this study, we compared the differences in distribution patterns and regional quantities of OT and/or AVP staining in the forebrains of wild and laboratory strains of rats and mice. Our results indicated that, in the anterior hypothalamus (AH), laboratory strains showed significantly higher densities of OT-ir (immunoreactive) and AVP-ir cells than wild strains, while no significant difference in the densities of those cells in the lateral hypothalamus (LH) was detected between wild and laboratory strains. Laboratory strains showed higher densities of OT-ir and AVP-ir cells than wild strains in the medial preoptic area (MPOA), and differed in almost every MPOA subnucleus. Our results suggest that domestication significantly alters the expression of OT and AVP in related brain areas of laboratory rats and mice, an observation that could explain the identified changes in behavioral patterns. PMID:26553093

  5. Transcriptomic Analyses Reveal Novel Genes with Sexually Dimorphic Expression in Yellow Catfish (Pelteobagrus fulvidraco) Brain.

    Science.gov (United States)

    Lu, Jianguo; Zheng, Min; Zheng, Jiajia; Liu, Jian; Liu, Yongzhuang; Peng, Lina; Wang, Pingping; Zhang, Xiaofeng; Wang, Qiushi; Luan, Peixian; Mahbooband, Shahid; Sun, Xiaowen

    2015-10-01

    Yellow catfish (Pelteobagrus fulvidraco) is a pivotal freshwater aquaculture species in China. It shows sexual size dimorphism favoring male in growth. Whole transcriptome approach is required to get the overview of genetic toolkit for understanding the sex determination mechanism aiming at devising its monosex production. Beside gonads, the brain is also considered as a major organ for vertebrate reproduction. Transcriptomic analyses on the brain and of different developmental stages will provide the dynamic view necessary for better understanding its sex determination. In this regard, we have performed a de novo assembly of yellow catfish brain transcriptome by high throughput Illumina sequencing. A total number of 154,507 contigs were obtained with the lengths ranging from 201 to 27,822 bp and N50 of 2,101 bp, as well as 20,699 unigenes were identified. Of these unigenes, 13 and 54 unigenes were detected to be XY-specifically expressed genes (SEGs) for one and 2-year-old yellow catfish, while the corresponding numbers of XX-SEGs for those two stages were 19 and 13, respectively. Our work identifies a set of annotated genes that are candidate factors affecting sexual dimorphism as well as simple sequence repeat (SSR) and single nucleotide variation (SNV) in yellow catfish. To validate the expression patterns of the sex-related genes, we performed quantitative real-time PCR (qRT-PCR) indicating the reliability and accuracy of our analysis. The results in our study may enhance our understanding of yellow catfish sex determination and potentially help to improve the production of all-male yellow catfish for aquaculture. PMID:26242754

  6. To what extent is blood a reasonable surrogate for brain in gene expression studies: estimation from mouse hippocampus and spleen

    Directory of Open Access Journals (Sweden)

    MatthewNDavies

    2009-10-01

    Full Text Available Microarrays are designed to measure genome-wide differences in gene expression. In cases where a tissue is not accessible for analysis (e.g. human brain, it is of interest to determine whether a second, accessible tissue could be used as a surrogate for transcription profiling. Surrogacy has applications in the study of behavioural and neurodegenerative disorders. Comparison between hippocampus and spleen mRNA obtained from a mouse recombinant inbred panel indicates a high degree of correlation between the tissues for genes that display a high heritability of expression level. This correlation is not limited to apparent expression differences caused by sequence polymorphisms in the target sequences and includes both cis and trans genetic effects. A tissue such as blood could therefore give surrogate information on expression in brain for a subset of genes, in particular those co-expressed between the two tissues, which have heritably varying expression.

  7. Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1 Expression at the Blood-Brain Barrier in Mice

    Directory of Open Access Journals (Sweden)

    Anja Brenn

    2011-01-01

    Full Text Available Neurovascular dysfunction is an important component of Alzheimer's disease, leading to reduced clearance across the blood-brain barrier and accumulation of neurotoxic β-amyloid (Aβ peptides in the brain. It has been shown that the ABC transport protein P-glycoprotein (P-gp, ABCB1 is involved in the export of Aβ from the brain into the blood. To determine whether Aβ influences the expression of key Aβ transporters, we studied the effects of 1-day subcutaneous Aβ1-40 and Aβ1-42 administration via Alzet mini-osmotic pumps on P-gp, BCRP, LRP1, and RAGE expression in the brain of 90-day-old male FVB mice. Our results demonstrate significantly reduced P-gp, LRP1, and RAGE mRNA expression in mice treated with Aβ1-42 compared to controls, while BCRP expression was not affected. The expression of the four proteins was unchanged in mice treated with Aβ1-40 or reverse-sequence peptides. These findings indicate that, in addition to the age-related decrease of P-gp expression, Aβ1-42 itself downregulates the expression of P-gp and other Aβ-transporters, which could exacerbate the intracerebral accumulation of Aβ and thereby accelerate neurodegeneration in Alzheimer's disease and cerebral β-amyloid angiopathy.

  8. Transient and persistent expression of NT-3/HDNF mRNA in the rat brain during postnatal development.

    Science.gov (United States)

    Friedman, W J; Ernfors, P; Persson, H

    1991-06-01

    Neurotrophin-3 (NT-3) is closely related to two known neurotrophic agents, NGF and brain-derived neurotrophic factor (BDNF), and acts upon overlapping, yet distinct, populations of peripheral ganglia. NT-3 mRNA expression in the adult rat brain is largely confined to the hippocampus. In this study, we have used in situ hybridization to examine expression of this novel neurotrophic factor during postnatal development. The striking observation was made that NT-3 mRNA was transiently expressed at high levels in the cingulate cortex during the first 2 weeks of age. In the hippocampus, the adult pattern of expression, in the CA2, medial CA1, and granule layer of the dentate gyrus, was detected at all ages examined. However, there were two major differences in NT-3 mRNA expression in the developing hippocampus: Labeled cells were detected in the hilar region of the dentate gyrus at postnatal day 1 (P1) and 1 week that were absent by 2 weeks of age. Further, the caudal hippocampus, which has a lower intensity of labeling than the rostral region in the adult, was devoid of NT-3-expressing cells in the P1 and 1-week-old rat brain. These data indicate a substantial plasticity in NT-3 mRNA expression and suggest that the spectrum of neurons supported by NT-3 during development is partially different from that in the mature rat brain. PMID:2045877

  9. Identification of Vulnerable Cell Types in Major Brain Disorders Using Single Cell Transcriptomes and Expression Weighted Cell Type Enrichment

    OpenAIRE

    Skene, Nathan G.; Grant, Seth G.N.

    2016-01-01

    The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment ...

  10. Identification of vulnerable cell types in major brain disorders using single cell transcriptomes and expression weighted cell type enrichment

    OpenAIRE

    Skene, Nathan G.; Grant, Seth G.N.

    2016-01-01

    The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment ...

  11. Distinct patterns of spread of prion infection in brains of mice expressing anchorless or anchored forms of prion protein

    OpenAIRE

    Rangel, Alejandra; Race, Brent; Phillips, Katie; Striebel, James; Kurtz, Nancy; Chesebro, Bruce

    2014-01-01

    Background In humans and animals, prion protein (PrP) is usually expressed as a glycophosphatidylinositol (GPI)-anchored membrane protein, but anchorless PrP may be pathogenic in humans with certain familial prion diseases. Anchored PrP expressed on neurons mediates spread of prions along axons in the peripheral and central nervous systems. However, the mechanism of prion spread in individuals expressing anchorless PrP is poorly understood. Here we studied prion spread within brain of mice ex...

  12. Developmentally Regulated Expression of the Nerve Growth Factor Receptor Gene in the Periphery and Brain

    Science.gov (United States)

    Buck, C. R.; Martinez, Humberto J.; Black, Ira B.; Chao, Moses V.

    1987-05-01

    Nerve growth factor (NGF) regulates development and maintenance of function of peripheral sympathetic and sensory neurons. A potential role for the trophic factor in brain has been detected only recently. The ability of a cell to respond to NGF is due, in part, to expression of specific receptors on the cell surface. To study tissue-specific expression of the NGF receptor gene, we have used sensitive cRNA probes for detection of NGF receptor mRNA. Our studies indicate that the receptor gene is selectively and specifically expressed in sympathetic (superior cervical) and sensory (dorsal root) ganglia in the periphery, and by the septum-basal forebrain centrally, in the neonatal rat in vivo. Moreover, examination of tissues from neonatal and adult rats reveals a marked reduction in steady-state NGF receptor mRNA levels in sensory ganglia. In contrast, a 2- to 4-fold increase was observed in the basal forebrain and in the sympathetic ganglia over the same time period. Our observations suggest that NGF receptor mRNA expression is developmentally regulated in specific areas of the nervous system in a differential fashion.

  13. Gender and environmental enrichment impact dopamine transporter expression after experimental traumatic brain injury.

    Science.gov (United States)

    Wagner, Amy K; Chen, Xiangbai; Kline, Anthony E; Li, Youming; Zafonte, Ross D; Dixon, C Edward

    2005-10-01

    Dopamine (DA) systems are implicated in cognitive deficits following traumatic brain injury (TBI). Rodent studies have demonstrated that both environmental enrichment (EE) and sex hormones can influence DA systems. The dopamine transporter (DAT) plays a crucial role in regulating DA transmission, and previous work shows that DAT is decreased after TBI in males. Therefore, the purpose of this study was to examine the effects of gender and EE on frontal cortex and striatal DAT expression after TBI. Sprague-Dawley male (n = 24) and cycling female rats (n = 24) were placed into EE or standard housing after controlled cortical impact (2.7 mm, 4.0 m/s) injury or sham surgery (eight groups, n = 6/group). Four weeks post-surgery, bilateral frontal cortex and striatal DAT expression was examined via Western blot. Results demonstrated that there was a significant effect of injury, EE, and region on DAT expression (P effect of injury, EE, and region for male groups (P effects on post-injury DAT expression for females than males. These findings may have some relevance to treatment paradigms using dopaminergic neurostimulants after TBI. PMID:16023635

  14. Gene expression alterations in brains of mice infected with three strains of scrapie

    Directory of Open Access Journals (Sweden)

    Race Richard E

    2006-05-01

    Full Text Available Abstract Background Transmissible spongiform encephalopathies (TSEs or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD in humans, bovine spongiform encephalopathy (BSE in cattle, chronic wasting disease (CWD in deer and elk, and scrapie in sheep, and experimental mice. To gain insights into TSE pathogenesis, we made and used cDNA microarrays to identify disease-associated alterations in gene expression. Brain gene expression in scrapie-infected mice was compared to mock-infected mice at pre-symptomatic and symptomatic time points. Three strains of mouse scrapie that show striking differences in neuropathology were studied: ME7, 22L, and Chandler/RML. Results In symptomatic mice, over 400 significant gene expression alterations were identified. In contrast, only 22 genes showed significant alteration in the pre-symptomatic animals. We also identified genes that showed significant differences in alterations in gene expression between strains. Genes identified in this study encode proteins that are involved in many cellular processes including protein folding, endosome/lysosome function, immunity, synapse function, metal ion binding, calcium regulation and cytoskeletal function. Conclusion These studies shed light on the complex molecular events that occur during prion disease, and identify genes whose further study may yield new insights into strain specific neuropathogenesis and ante-mortem tests for TSEs.

  15. GFAP expression is regulated by Pax3 in brain glioma stem cells.

    Science.gov (United States)

    Su, Xing; Liu, Xiaojiang; Ni, Lanchun; Shi, Wei; Zhu, Hui; Shi, Jinlong; Chen, Jian; Gu, Zhikai; Gao, Yilu; Lan, Qing; Huang, Qingfeng

    2016-09-01

    Glioblastomas are understood to evolve from brain glioma stem cells (BGSCs), and yet the biology underlying this model of tumorigenesis is largely unknown. Paired box 3 protein (Pax3) is a member of the paired box (Pax) family of transcription factors that is normally expressed during embryonic development, but has recently been implicated in tumorigenesis. The present study demonstrated that Pax3 is differentially expressed in U87MG human glioma cell, BGSC and normal 1800 human astrocyte lines. Herein, we identified that the glial fibrillary acidic protein (GFAP), a major intermediate filament protein of mature astrocytes, is directly downregulated during the differentiation of BGSCs via the binding of Pax3 to the promoter region of GFAP. Moreover, siRNA silencing of Pax3 arrested BGSC differentiation, while overexpression of Pax3 promoted the differentiation in BGSCs. Furthermore, we studied the cell proliferation, invasion, apoptosis, differentiation and expression of Pax3 and GFAP in Pax3 siRNA-knockdown and Pax3-overexpressing BGSC models by CCK-8, Transwell migration, flow cytometry and western blot assays. The results indicate that Pax3 regulates GFAP expression, and that Pax3 may contribute to the evolution of BGSCs towards malignancy. PMID:27432276

  16. Effects of Different Doses of Levetiracetam on Aquaporin 4 Expression in Rats with Brain Edema Following Fluid Percussion Injury.

    Science.gov (United States)

    Jin, Hongbo; Li, Wenling; Dong, Changzheng; Ma, Li; Wu, Jiang; Zhao, Wenqing

    2016-01-01

    BACKGROUND This study was designed to investigate the effects of different doses of levetiracetam on aquaporin 4 (AQP4) expression in rats after fluid percussion injury. MATERIAL AND METHODS Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, traumatic brain injury group, low-dose levetiracetam group, and high-dose levetiracetam group. Brain edema models were established by fluid percussion injury, and intervened by the administration of levetiracetam. Samples from the 4 groups were collected at 2, 6, 12, and 24 h, and at 3 and 7 days after injury. Histological observation was performed using hematoxylin-eosin staining and immunohistochemical staining. AQP4 and AQP4 mRNA expression was detected using Western blot assay and RT-PCR. Brain water content was measured by the dry-wet method. RESULTS Compared with the traumatic brain injury group, brain water content, AQP4 expression, and AQP4 mRNA expression were lower in the levetiracetam groups at each time point and the differences were statistically significant (Ppercussion injury by down-regulating AQP4 and AQP4 mRNA expression. There is a dose-effect relationship in the preventive effect of levetiracetam within a certain extent. PMID:26927633

  17. Expression of aggregative adherence to hela cells by Escherichia coli strains isolated from sick horses Expressão de aderência agregativa em células HeLa por amostras de E. coli isoladas de eqüinos doentes

    Directory of Open Access Journals (Sweden)

    Ana Maria Alvim Liberatore

    2007-03-01

    Full Text Available The virulence attributes of 56 Escherichia coli strains isolated from sick horses (secretions of uterine cervices; gastrointestinal and lung fragments of necropsy; diarrheic feces, and tracheal washings was examined by determining their adherence pattern to HeLa cells and searching for the presence of virulence genes of the various E. coli pathotypes. Two non-adherent strains presented astA, which encodes the enteroaggregative E. coli heat-stable toxin. Twenty-seven strains (48.2% adhered to HeLa cells, 21 (77.8% of which presented the aggregative adherence pattern (AA that characterize the Enteroaggregative E. coli pathotype (EAEC. Nine of the strains presenting AA were isolated from secretions of uterine cervix, including one carrying virulence genes of the EAEC pathotype (aggR,aap,irp2, and pic. This is the first description of the AA phenotype amongst E. coli strains from sick horses. Such strains should be further evaluated regarding their potential role in the pathogenesis of diverse equine diseases and as reservoirs of human infections.Características de virulência de 56 amostras de Escherichia coli isoladas de eqüinos doentes (secreção de colo uterino, fragmentos de necrópsia do trato gastrointestinal e de pulmões, fezes diarréicas e lavado traqueal foram examinadas para determinar o padrão de aderência em células HeLa e pesquisar a presença de genes de virulência de vários patotipos de E. coli. Duas amostras não aderentes apresentaram astA, gene que codifica a toxina termo-estável de E. coli enteroagregativa. Das vinte e sete amostras (48,2% que aderiram a células HeLa, 21 (77,8% apresentaram o padrão de aderência agregativa (AA que caracteriza o patotipo de E. coli Enteroagregativa (EAEC. Nove destas amostras que apresentaram AA foram isoladas de secreção de colo uterino, incluindo uma que apresentava genes de virulência de patotipos de EAEC (aggR,aap,irp2 e pic. Esta é a primeira descrição do fenótipo AA em

  18. An optimized ERP brain-computer interface based on facial expression changes

    Science.gov (United States)

    Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

    2014-06-01

    Objective. Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Approach. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. Main results. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be

  19. Hypoxia regulates Toll-like receptor-9 expression and invasive function in human brain cancer cells in vitro

    Science.gov (United States)

    SANDHOLM, JOUKO; TUOMELA, JOHANNA; KAUPPILA, JOONAS H.; HARRIS, KEVIN W.; GRAVES, DAVID; SELANDER, KATRI S.

    2014-01-01

    Toll-like receptor-9 (TLR9) is a cellular DNA sensor of the innate immune system. TLR9 is widely expressed in a number of tumors, including brain cancer; however, little is known regarding its regulation and involvement in cancer pathophysiology. The present study demonstrated that hypoxia upregulates and downregulates TLR9 expression in human brain cancer cells in vitro, in a cell-specific manner. In addition, hypoxia-induced TLR9 upregulation was associated with hypoxia-induced invasion; however, such invasion was not detected in cells where hypoxia had suppressed TLR9 expression. Furthermore, suppression of TLR9 expression through TLR9 siRNA resulted in an upregulation of matrix metalloproteinase (MMP)-2, -9 and -13 and tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) mRNA, and a decreased invasion of cells in normoxia, in a cell-specific manner. In cells where hypoxia induced TLR9 expression, TLR9 expression and invasion were reduced by TLR9 siRNA. The decreased invasion observed in hypoxia was associated with the decreased expression of the MMPs and a concomitant increase in TIMP-3 expression. In conclusion, hypoxia regulates the invasion of brain cancer cells in vitro in a TLR9-dependent manner, which is considered to be associated with a complex expression pattern of TLR9-regulated mediators and inhibitors of invasion. PMID:24959259

  20. CART peptide and opioid addiction: Expression changes in male rat brain.

    Science.gov (United States)

    Bakhtazad, A; Vousooghi, N; Garmabi, B; Zarrindast, M R

    2016-06-14

    Previous studies have shown the prominence of cocaine- and amphetamine-regulated transcript (CART) peptide in rewarding and reinforcing effects of drugs of abuse specially psychostimulants. The data regarding the effects of different stages of opioid addiction on CART expression and the interconnection between CART and opioids are not much available. Here we have studied the changes in the expression level of CART mRNA and protein in various parts of the brain reward pathway in different stages of opioid addiction. Groups of male rats received acute low-dose (10mg/kg), acute high-dose (80mg/kg) and chronic escalating doses of morphine. In addition, withdrawal and abstinence states were evaluated after injection of naloxone (1mg/kg) and long-term maintenance of addicted animals, respectively. Expression of CART mRNA in the brain was measured by real-time PCR method. Western blotting was used to quantify the protein level. CART mRNA and protein were both up-regulated in high-dose morphine-administered animals and also in the withdrawal group in the nucleus accumbens (NAc), striatum and prefrontal cortex (PFC). In the addicted group, CART mRNA and protein were both down-regulated in NAc and striatum. In the abstinent group, CART mRNA was down-regulated in NAc. In the hippocampus, the only observed change was the up-regulation of CART mRNA in the withdrawal group. We suggest that the modulatory role of CART peptide in rewarding and reinforcing effects of opioids weakens when opioids are used for a long time and is stimulated when acute stress such as naloxone-induced withdrawal syndrome or acute high-dose administration of morphine occurs to the animal. PMID:26955782

  1. Metallothionein (MT -I and MT-II expression are induced and cause zinc sequestration in the liver after brain injury.

    Directory of Open Access Journals (Sweden)

    Michael W Pankhurst

    Full Text Available UNLABELLED: Experiments with transgenic over-expressing, and null mutant mice have determined that metallothionein-I and -II (MT-I/II are protective after brain injury. MT-I/II is primarily a zinc-binding protein and it is not known how it provides neuroprotection to the injured brain or where MT-I/II acts to have its effects. MT-I/II is often expressed in the liver under stressful conditions but to date, measurement of MT-I/II expression after brain injury has focused primarily on the injured brain itself. In the present study we measured MT-I/II expression in the liver of mice after cryolesion brain injury by quantitative reverse-transcriptase PCR (RT-PCR and enzyme-linked immunosorbent assay (ELISA with the UC1MT antibody. Displacement curves constructed using MT-I/II knockout (MT-I/II(-/- mouse tissues were used to validate the ELISA. Hepatic MT-I and MT-II mRNA levels were significantly increased within 24 hours of brain injury but hepatic MT-I/II protein levels were not significantly increased until 3 days post injury (DPI and were maximal at the end of the experimental period, 7 DPI. Hepatic zinc content was measured by atomic absorption spectroscopy and was found to decrease at 1 and 3 DPI but returned to normal by 7DPI. Zinc in the livers of MT-I/II(-/- mice did not show a return to normal at 7 DPI which suggests that after brain injury, MT-I/II is responsible for sequestering elevated levels of zinc to the liver. CONCLUSION: MT-I/II is up-regulated in the liver after brain injury and modulates the amount of zinc that is sequestered to the liver.

  2. Effect of dietary fat and the circadian clock on the expression of brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

    2016-07-15

    Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the brain and its decreased levels are associated with the development of obesity and neurodegeneration. Our aim was to test the effect of dietary fat, its timing and the circadian clock on the expression of BDNF and associated signaling pathways in mouse brain and liver. Bdnf mRNA oscillated robustly in brain and liver, but with a 12-h shift between the tissues. Brain and liver Bdnf mRNA showed a 12-h phase shift when fed ketogenic diet (KD) compared with high-fat diet (HFD) or low-fat diet (LFD). Brain or liver Bdnf mRNA did not show the typical phase advance usually seen under time-restricted feeding (RF). Clock knockdown in HT-4 hippocampal neurons led to 86% up-regulation of Bdnf mRNA, whereas it led to 60% down-regulation in AML-12 hepatocytes. Dietary fat in mice or cultured hepatocytes and hippocampal neurons led to increased Bdnf mRNA expression. At the protein level, HFD increased the ratio of the mature BDNF protein (mBDNF) to its precursor (proBDNF). In the liver, RF under LFD or HFD reduced the mBDNF/proBDNF ratio. In the brain, the two signaling pathways related to BDNF, mTOR and AMPK, showed reduced and increased levels, respectively, under timed HFD. In the liver, the reverse was achieved. In summary, Bdnf expression is mediated by the circadian clock and dietary fat. Although RF does not affect its expression phase, in the brain, when combined with high-fat diet, it leads to a unique metabolic state in which AMPK is activated, mTOR is down-regulated and the levels of mBDNF are high. PMID:27113028

  3. Chasing Migration Genes: A Brain Expressed Sequence Tag Resource for Summer and Migratory Monarch Butterflies (Danaus plexippus)

    OpenAIRE

    Haisun Zhu; Amy Casselman; Reppert, Steven M.

    2008-01-01

    North American monarch butterflies (Danaus plexippus) undergo a spectacular fall migration. In contrast to summer butterflies, migrants are juvenile hormone (JH) deficient, which leads to reproductive diapause and increased longevity. Migrants also utilize time-compensated sun compass orientation to help them navigate to their overwintering grounds. Here, we describe a brain expressed sequence tag (EST) resource to identify genes involved in migratory behaviors. A brain EST library was constr...

  4. Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer

    Directory of Open Access Journals (Sweden)

    Mokbel Kefah

    2011-07-01

    Full Text Available Abstract Introduction Brain-derived neurotrophic factor (BDNF has established physiological roles in the development and function of the vertebrate nervous system. BDNF has also been implicated in several human malignancies, including breast cancer (BC. However, the precise biological role of BDNF and its utility as a novel biomarker have yet to be determined. The objective of this study was to determine the mRNA and protein expression of BDNF in a cohort of women with BC. Expression levels were compared with normal background tissues and evaluated against established pathological parameters and clinical outcome over a 10 year follow-up period. Methods BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription, BDNF transcript levels were determined using real-time quantitative PCR. BDNF protein expression in mammary tissues was assessed with standard immuno-histochemical methodology. Expression levels were analyzed against tumour size, grade, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI and clinical outcome over a 10 year follow-up period. Results Immuno-histochemical staining revealed substantially greater BDNF expression within neoplastic cells, compared to normal mammary epithelial cells. Significantly higher mRNA transcript levels were found in the BC specimens compared to background tissues (p = 0.007. The expression of BDNF mRNA was demonstrated to increase with increasing NPI; NPI-1 vs. NPI-2 (p = 0.009. Increased BDNF transcript levels were found to be significantly associated with nodal positivity (p = 0.047. Compared to patients who remained disease free, higher BDNF expression was significantly associated with local recurrence (LR (p = 0.0014, death from BC (p = 0.018 and poor prognosis overall (p = 0.013. After a median follow up of 10 years, higher BDNF expression levels were significantly associated with reduced overall survival (OS (106 vs. 136 months, p = 0.006. BDNF

  5. Regional variation in expression of acetylcholinesterase mRNA in adult rat brain analyzed by in situ hybridization.

    OpenAIRE

    Hammond, P; Rao, R; Koenigsberger, C; Brimijoin, S

    1994-01-01

    To investigate the molecular basis of regional variation in expression of brain acetylcholinesterase (AChE; EC 3.1.1.7), steady-state levels of AChE activity and mRNA were examined. Relative AChE activity in Triton extracts from six areas of the rat brain varied as follows: cortex < cerebellum < medulla < pons-midbrain < thalamus < striatum. In contralateral samples from the same brains, AChE mRNA was assessed by Northern blotting with random-primed 32P-labeled cDNA. The regional abundance of...

  6. Non-negative Tensor Factorization with missing data for the modeling of gene expressions in the Human Brain

    DEFF Research Database (Denmark)

    Nielsen, Søren Føns Vind; Mørup, Morten

    2014-01-01

    Non-negative Tensor Factorization (NTF) has become a prominent tool for analyzing high dimensional multi-way structured data. In this paper we set out to analyze gene expression across brain regions in multiple subjects based on data from the Allen Human Brain Atlas [1] with more than 40 % data...... missing from all subjects the model based predictions are useful. When analyzing the structure of the components derived for one of the best predicting model orders the components identified in general constitute localized regions of the brain. Non-negative tensor factorization based on marginalization...

  7. Acacia ferruginea inhibits inflammation by regulating inflammatory iNOS and COX-2.

    Science.gov (United States)

    Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2016-01-01

    Inflammation is a local defensive reaction of a host to cellular injury or infection. Prolonged inflammation can contribute to pathogenesis of many disorders. Identification of naturally occurring phytoconstituents that can suppress inflammatory mediators can lead to the discovery of anti-inflammatory therapeutics. Acacia ferruginea is used traditionally to treat numerous ailments including hemorrhage, irritable bowel syndrome and leprosy. The present study evaluated the anti-inflammatory activity of A. ferruginea extract against acute (carrageenan) and chronic (formaldehyde) inflammation in Balb/c mice. Pre-treatment with A. ferruginea extract (10 mg/kg BW) for 5 consecutive days via intraperitonial (IP) administration significantly inhibited subsequent induction of paw edema in both models; the effects were comparable to that of the standard drug indomethacin. The results also showed the A. ferruginea extract significantly inhibited nitric oxide (NO) synthesis and iNOS expression (as measured in serum), diminished inflammation in - and neutrophil infiltration to - the paw tissues and led to a reduction in the number of COX-2(+) immunoreative cells (as evidenced by histologic and immunohistochemical analyses) in the paws relative to those in paws of mice that received the irritants only. Further, in vitro studies showed the extract could significantly scavenge free radicals generated as in DPPH and NO radical generating assays. Taken together, the results showed that A. ferruginea extract imparted potent anti-oxidant and -inflammatory effects, in part by maintaining oxidative homeostasis, inhibiting NO synthesis and suppressing iNOS and COX-2 expression and so could potentially be exploited as a potential plant-based medication against inflammatory disorders. PMID:25738525

  8. A rat model of smoke inhalation injury: Influence of combustion smoke on gene expression in the brain

    International Nuclear Information System (INIS)

    Acute smoke inhalation causes death and injury in victims of home and industrial fires as well as victims of combat situations. The lethal factors in combustion smoke inhalation are toxic gases and oxygen deficiency, with carbon monoxide (CO) as a primary cause of death. In survivors, inhalation of smoke can result in severe immediate and delayed neuropathologies. To gain insight into the progression of molecular events contributing to smoke inhalation sequelae in the brain, we developed a smoke inhalation rat model and conducted a genome-wide analysis of gene expression. Microarray analysis revealed a modified brain transcriptome with changes peaking at 24 h and subsiding within 7 days post-smoke. Overall, smoke inhalation downregulated genes associated with synaptic function, neurotransmission, and neurotrophic support, and upregulated genes associated with stress responses, including nitric oxide synthesis, antioxidant defenses, proteolysis, inflammatory response, and glial activation. Notably, among the affected genes, many have been previously implicated in other types of brain injury, demonstrating the usefulness of microarrays for analysis of changes in gene expression in complex insults. In accord with previously described modulations of nitric oxide homeostasis in CO poisoning, microarray analysis revealed increased brain expression of nitric oxide synthase (NOS) and NOS ligand after inhalation of smoke. Furthermore, immunostaining showed significant elevations in perivascular NOS and in protein nitration, corroborating the involvement of nitric oxide perturbations in post-smoke sequelae in the brain. Thus, the new rat model, in combination with microarray analyses, affords insight into the complex molecular pathophysiology of smoke inhalation in the brain

  9. EXPRESSION OF SV40 Tag AND FORMATION Tag-p53 AND Tag-Rb COMPLEXES IN CHINESE BRAIN TUMORS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the expression of SV40 Tag andformation of Tag-p53 and Tag-Rb complexes in Chinese brain tumors. Methods: SV40 large tumor antigen (Tag) were investigated by immunoprecipitation, silver staining and Western blot in 65 cases of Chinese brain tumors and 8 cases of normal brain tissues. Tag-p53 and Tag-Rb complexes were screened by the same way in 20 and 15 Tag positive tumor tissues respectively. Results: Tag was found in all of 8 ependymomas and 2 choroid plexus papillomas, 90% (9/10) of pituitary adenomas, 73% (11/15) of astrocytomas, 70% (7/10) of meningiomas, 50% (4/8) of glioblastoma multiform, 33% (2/6) of medulloblastomas, 5 oligodendrogliomas, 1 pineocytoma and 8 normal brain tissues were negative for Tag. Tag-p53 complex was detected in all of 20 Tag positive tumors as well as Tag-Rb complex in all of 15 Tag positive tumors. Conclusion: SV40 Tag is not only expressed in human brain tumors, but also it can form specific complexes with tumor suppressors p53 and Rb. SV40 is correlated to human brain tumorigenesis. The inactivation of p53 and Rb due to the formation of Tag-p53 and Tag-Rb complexes is possibly an important mechanism in the etiopathogenesis of human brain tumors.

  10. Nitrosyl iodide, INO: A combined ab initio and high-resolution spectroscopic study

    Science.gov (United States)

    Bailleux, S.; Duflot, D.; Aiba, S.; Nakahama, S.; Ozeki, H.

    2016-04-01

    In the nitrosyl halides series (XNO, where X = F, Cl, Br, I), INO is the only chemical species whose rotational spectrum has not been reported. Nitrosyl iodide, together with the nitryl (INO2), nitrite (IONO) and nitrate (IONO2) iodides, is believed to impact tropospheric ozone levels. Guided by our quantum chemical calculations, we report the detection of INO in the gas phase by high-resolution spectroscopy for the first time. INO was generated by mixing continuously I2 and NO. The measurement and least-squares analysis of 173 a-type rotational transitions resulted in the accurate determination of molecular parameters.

  11. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    DEFF Research Database (Denmark)

    Olesen, R H; Hyde, T M; Kleinman, J E;

    2016-01-01

    participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African...... available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins...... expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing...

  12. Correlation of Nr4a2 expression with the neuron progenitors in adult zebrafish brain.

    Science.gov (United States)

    Chen, Sheng; Luo, Guang Rui; Li, Ting; Liu, Ting Xi; Le, Weidong

    2013-11-01

    Our previous study showed that although Nr4a2b transcripts have little co-localization with tyrosine hydroxylase (TH) in the posterior tuberculum area, knockdown of Nr4a2 caused a decrease in the number of TH-positive (TH(+)) neurons in the posterior tuberculum area. It suggests that Nr4a2 expression in the progenitors may play an important role in regulating differentiation rather than survival of TH(+) progenitors in the posterior tuberculum area during early zebrafish embryogenesis. In this study, we determined the correlation between TH and Nr4a2 in adult zebrafish brain and found that Nr4a2b was co-localized with the spindle-shaped TH(+) cells in the posterior tuberculum area and some small round TH(+) cells in the pretectum area, but not with large pear-shaped TH(+) cells in adult zebrafish diencephalon. In the pretectum area, Nr4a2(+) cells were localized next to the dorsal side of TH(+) cells. Furthermore, we demonstrated that Nr4a2 was co-expressed with nestin in the progenitors of pretectum area and caudal periventricular hypothalamic zones with a lateral symmetry pattern beside the diencephalic ventricle. Co-expression of Nr4a2 and nestin in these areas was remarkably declined with aging. These findings indicate that Nr4a2 is expressed in the neuronal progenitors and plays a crucial role in the differentiation process of dopamine neuron from the stem cell. The change in Nr4a2 expression with aging suggests its possible association with neurodegenerative diseases. PMID:23842887

  13. Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.

    Science.gov (United States)

    Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G; Campbell, Ashley M; Saavedra, Juan M; Shewmaker, Frank P; Symes, Aviva J

    2015-10-01

    Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. PMID:26435412

  14. Expression of c-fos mRNA following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-fos mRNA in brain following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expression following percussion. METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury group. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa). The injury groups were then subdivided into 5 min, 15 min, 30 min, 1h, 2h groups according to the time elapsed after injury. The expression of c-fos mRNA was studied with reverse transcription polymerase chain reaction (RT-PCR) semi-quantitatively.RESULTS: At 5 min after percussion, the induction of c-fos mRNA was increased, and remained elevated up to 2 h after brain injury.CONCLUSION: The induction and expression of the c-fos mRNA in cortex and brain stem after fluid percussion brain injury were increased rapidly.

  15. Neuron-enriched gene expression patterns are regionally anti-correlated with oligodendrocyte-enriched patterns in the adult mouse and human brain

    Directory of Open Access Journals (Sweden)

    Powell PatrickChengTan

    2013-02-01

    Full Text Available An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia-to-neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

  16. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Wenda Xue

    2013-01-01

    Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

  17. Reconstructing Generalized Logical Networks of Transcriptional Regulation in Mouse Brain from Temporal Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Lodowski Kerrie H

    2009-01-01

    Full Text Available Gene expression time course data can be used not only to detect differentially expressed genes but also to find temporal associations among genes. The problem of reconstructing generalized logical networks to account for temporal dependencies among genes and environmental stimuli from transcriptomic data is addressed. A network reconstruction algorithm was developed that uses statistical significance as a criterion for network selection to avoid false-positive interactions arising from pure chance. The multinomial hypothesis testing-based network reconstruction allows for explicit specification of the false-positive rate, unique from all extant network inference algorithms. The method is superior to dynamic Bayesian network modeling in a simulation study. Temporal gene expression data from the brains of alcohol-treated mice in an analysis of the molecular response to alcohol are used for modeling. Genes from major neuronal pathways are identified as putative components of the alcohol response mechanism. Nine of these genes have associations with alcohol reported in literature. Several other potentially relevant genes, compatible with independent results from literature mining, may play a role in the response to alcohol. Additional, previously unknown gene interactions were discovered that, subject to biological verification, may offer new clues in the search for the elusive molecular mechanisms of alcoholism.

  18. In silico analysis of histone H3 gene expression during human brain development.

    Science.gov (United States)

    Ren, Megan; van Nocker, Steve

    2016-01-01

    Precise regulation of chromatin structure is essential for proper development of higher eukaryotes, and methylation of histone H3 at lysine-27 (H3K27) by the Polycomb Repressive Complex 2 (PRC2) component EZH2 has emerged as an important and conserved mechanism to ensure silencing of developmentally regulated genes. Recurrent mutations within the histone H3 genes H3F3A and HIST1H3B that convert K27 to methionine (H3K27M) and disrupt the global H3K27 methylation landscape and PRC2-dependent silencing, have recently been identified in pediatric high-grade gliomas including Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma multiforme (GBM; Type IV glioma). These findings have generated renewed interest in the dynamics of histone genes and their expression, which have been difficult to study due to redundancy and high sequence homology within the H3 gene family. In this in silico study, we re-evaluated genomic organization of the human H3 gene family and expression of these genes in the human brain, utilizing public RNA-based sequence datasets for the human genome and brain development. We identified transcriptional activity from at least 17 protein-encoding H3 genes in the developing brain, comprising at least 14 canonical (H3.1)-like and 3 'replication-independent' (H3.3)-like forms, and encoding six distinct H3 isoforms. Transcripts for H3.3 genes including H3F3A show gradual decrease in abundance associated with developmental progression, whereas H3.1 transcripts including HIST1H3B tend to be strongly downregulated at an early prenatal stage and remain essentially silent thereafter. Twelve genes, including members of both H3.1 and H3.3 classes, contain a K27-AAG codon that is mutable to that for M (ATG), whereas the remaining contain the alternative, AAA codon for K at this position. H3F3A is the only H3.3-like gene containing the K27-AAG codon, whereas HIST1H3B is among ten H3.1-like genes containing this codon. This data indicates that, in the early

  19. Effect of Long-Term Intake of Y3+ in Drinking Water on Gene Expression in Brains of Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The rats were fed with water dissolved Y3 + at different levels (0, 53.4, 5340 mg· L- 1 ) for 7 months. The gene expression in brain tissue was detected with oligonucleotide microarray. The results show that, compared to the control,789 genes express differentially, 507 over-expressed genes and 282 under-expressed genes in the high-dose group (5340found to express differentially including 32 over-expressed genes and 12 under-expressed genes in the low-dose group (53.sults suggest that Y3 + can change the expression of some genes, which may be responsible for the toxicity of rare earths on learning and memory.

  20. The clinical analysis of expression levels of IL-6, BNP and CRP in patients with brain injury

    Institute of Scientific and Technical Information of China (English)

    Jun-Feng Zhang

    2015-01-01

    Objective: To investigate the clinical analysis of expression levels of brain natriuretic peptide (BNP), interleukin -6 (IL-6), C-reactive protein (CRP) in patients with traumatic brain injury and its clinical significance. Methods: The levels of IL-6, BNP, CRP of 80 cases of traumatic brain injury and 80 cases of healthy people group were determined with radioimmunoassay and immunoassays. Results: The levels of IL-6 and CRP of patients with traumatic brain injury were higher than healthy people group (P<0.05), while the levels of BNP of patients with traumatic brain injury were lower than healthy people group (P<0.05). The levels of CRP and IL-6 of patients with severe were higher than light and moderate traumatic brain injury patients (P<0.05) .Compared with the time of admission, the serum BNP, IL-6 and -CRP levels of the patient admitted to hospital within 24 h reached a peak and gradually decreased in 3d after admission, compared with the previous admission, the difference was statistically significant (P<0.05). The levels of BNP of the severe were lower than light and moderate traumatic brain injury patients (P<0.05). Conclusions: The measurement of serum BNP, IL-6 and CRP levels will help to evaluate the extent of disease in elderly patients with traumatic brain injury and prognosis.

  1. Data on Arc and Zif268 expression in the brain of the α-2A adrenergic receptor knockout mouse.

    Science.gov (United States)

    Sanders, Jeff

    2016-06-01

    The α2-adrenergic receptor (α2-AR) is widely distributed in the brain with distinct roles for α2-AR subtypes (A, B and C). In this article, data are provided on Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 expression in the brain of the α2A-AR knockout (α2A-AR KO) mouse. These data are supplemental to an original research article examining Arc and Zif268 expression in rats injected with the α2-AR antagonist, RX821002 (http://dx.doi.org/10.1016/j.neulet.2015.12.002. [1]). PMID:26952134

  2. Strain differences in pH-sensitive K+ channel-expressing cells in chemosensory and nonchemosensory brain stem nuclei

    OpenAIRE

    Martino, Paul F.; Olesiak, S.; Batuuka, D.; Riley, D; Neumueller, S.; Forster, H. V.; Hodges, M. R.

    2014-01-01

    The ventilatory CO2 chemoreflex is inherently low in inbred Brown Norway (BN) rats compared with other strains, including inbred Dahl salt-sensitive (SS) rats. Since the brain stem expression of various pH-sensitive ion channels may be determinants of the CO2 chemoreflex, we tested the hypothesis that there would be fewer pH-sensitive K+ channel-expressing cells in BN relative to SS rats within brain stem sites associated with respiratory chemoreception, such as the nucleus tractus solitarius...

  3. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza;

    2015-01-01

    , the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin...... have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS...... mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in...

  4. Reconstructing Generalized Logical Networks of Transcriptional Regulation in Mouse Brain from Temporal Gene Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Song, Mingzhou (Joe) [New Mexico State University, Las Cruces; Lewis, Chris K. [New Mexico State University, Las Cruces; Lance, Eric [New Mexico State University, Las Cruces; Chesler, Elissa J [ORNL; Kirova, Roumyana [Bristol-Myers Squibb Pharmaceutical Research & Development, NJ; Langston, Michael A [University of Tennessee, Knoxville (UTK); Bergeson, Susan [Texas Tech University, Lubbock

    2009-01-01

    The problem of reconstructing generalized logical networks to account for temporal dependencies among genes and environmental stimuli from high-throughput transcriptomic data is addressed. A network reconstruction algorithm was developed that uses the statistical significance as a criterion for network selection to avoid false-positive interactions arising from pure chance. Using temporal gene expression data collected from the brains of alcohol-treated mice in an analysis of the molecular response to alcohol, this algorithm identified genes from a major neuronal pathway as putative components of the alcohol response mechanism. Three of these genes have known associations with alcohol in the literature. Several other potentially relevant genes, highlighted and agreeing with independent results from literature mining, may play a role in the response to alcohol. Additional, previously-unknown gene interactions were discovered that, subject to biological verification, may offer new clues in the search for the elusive molecular mechanisms of alcoholism.

  5. The Creatine Transporter Gene Paralogous at 16p11.2 Is Expressed in Human Brain

    Directory of Open Access Journals (Sweden)

    Nadia Bayou

    2008-01-01

    We report on the clinical, cytogenetic, and molecular findings in a boy with autism carrying a de novo translocation t(7;16(p22.1;p11.2. The chromosome 16 breakpoint disrupts the paralogous SLC6A8 gene also called SLC6A10 or CT2. Predicted translation of exons and RT-PCR analysis reveal specific expression of the creatine transporter paralogous in testis and brain. Several studies reported on the role of X-linked creatine transporter mutations in individuals with mental retardation, with or without autism. The existence of disruption in SLC6A8 paralogous gene associated with idiopathic autism suggests that this gene may be involved in the autistic phenotype in our patient.

  6. Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, Mercedes; Lago, Natalia;

    2003-01-01

    study demonstrated that transgenic IL-6 production significantly increased wound healing following the cryolesion. Thus, at 20 days postlesion (dpl) the GFAP-IL6 mice showed almost complete wound healing compared to litter mate nontransgenic controls. It seems likely that a reduced inflammatory response...... in the long term could be responsible for this IL-6-related effect. Thus, while in the acute phase following cryolesion (1-6 dpl) the recruitment of macrophages and T lymphocytes was higher in GFAP-IL6 mice, at 10-20 dpl it was significantly reduced compared to controls. Reactive astrogliosis was...... as to the transgenic IL-6-induced increase of the antioxidant, neuroprotective proteins metallothionein-I + II. These results indicate that although in the brain the chronic astrocyte-targeted expression of IL-6 spontaneously induces an inflammatory response causing significant damage, during an...

  7. Biological Computation Indexes of Brain Oscillations in Unattended Facial Expression Processing Based on Event-Related Synchronization/Desynchronization.

    Science.gov (United States)

    Yu, Bo; Ma, Lin; Li, Haifeng; Zhao, Lun; Bo, Hongjian; Wang, Xunda

    2016-01-01

    Estimation of human emotions from Electroencephalogram (EEG) signals plays a vital role in affective Brain Computer Interface (BCI). The present study investigated the different event-related synchronization (ERS) and event-related desynchronization (ERD) of typical brain oscillations in processing Facial Expressions under nonattentional condition. The results show that the lower-frequency bands are mainly used to update Facial Expressions and distinguish the deviant stimuli from the standard ones, whereas the higher-frequency bands are relevant to automatically processing different Facial Expressions. Accordingly, we set up the relations between each brain oscillation and processing unattended Facial Expressions by the measures of ERD and ERS. This research first reveals the contributions of each frequency band for comprehension of Facial Expressions in preattentive stage. It also evidences that participants have emotional experience under nonattentional condition. Therefore, the user's emotional state under nonattentional condition can be recognized in real time by the ERD/ERS computation indexes of different frequency bands of brain oscillations, which can be used in affective BCI to provide the user with more natural and friendly ways. PMID:27471545

  8. Biological Computation Indexes of Brain Oscillations in Unattended Facial Expression Processing Based on Event-Related Synchronization/Desynchronization

    Science.gov (United States)

    Ma, Lin; Li, Haifeng; Zhao, Lun; Bo, Hongjian; Wang, Xunda

    2016-01-01

    Estimation of human emotions from Electroencephalogram (EEG) signals plays a vital role in affective Brain Computer Interface (BCI). The present study investigated the different event-related synchronization (ERS) and event-related desynchronization (ERD) of typical brain oscillations in processing Facial Expressions under nonattentional condition. The results show that the lower-frequency bands are mainly used to update Facial Expressions and distinguish the deviant stimuli from the standard ones, whereas the higher-frequency bands are relevant to automatically processing different Facial Expressions. Accordingly, we set up the relations between each brain oscillation and processing unattended Facial Expressions by the measures of ERD and ERS. This research first reveals the contributions of each frequency band for comprehension of Facial Expressions in preattentive stage. It also evidences that participants have emotional experience under nonattentional condition. Therefore, the user's emotional state under nonattentional condition can be recognized in real time by the ERD/ERS computation indexes of different frequency bands of brain oscillations, which can be used in affective BCI to provide the user with more natural and friendly ways. PMID:27471545

  9. Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin

    Science.gov (United States)

    Hassel, Bjørnar; Taubøll, Erik; Shaw, Renee; Gjerstad, Leif; Dingledine, Ray

    2014-01-01

    Summary Purpose It is commonly assumed that antiepileptic drugs (AEDs) act similarly in the various parts of the brain as long as their molecular targets are present. A few experimental studies on metabolic effects of vigabatrin, levetiracetam, valproate, and lamotrigine have shown that these drugs may act differently in different brain regions. We examined effects of chronic treatment with levetiracetam or phenytoin on mRNA levels to detect regional drug effects in a broad, nonbiased manner. Methods mRNA levels were monitored in three brain regions with oligonucleotide-based microarrays. Results Levetiracetam (150 mg/kg for 90 days) changed the expression of 65 genes in pons/medulla oblongata, two in hippocampus, and one in frontal cortex. Phenytoin (75 mg/kg), in contrast, changed the expression of only three genes in pons/medulla oblongata, but 64 genes in hippocampus, and 327 genes in frontal cortex. Very little overlap between regions or drug treatments was observed with respect to effects on gene expression. Discussion We conclude that chronic treatment with levetiracetam or phenytoin causes region-specific and highly differential effects on gene expression in the brain. Regional effects on gene expression could reflect regional differences in molecular targets of AEDs, and they could influence the clinical profiles of AEDs. PMID:20345932

  10. miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) and their role during tumor development have been studied in great detail during the last decade, albeit their expression pattern and regulation during normal development are however not so well established. Previous studies have shown that miRNAs are differentially expressed in solid human tumors. Platelet-derived growth factor (PDGF) signaling is known to be involved in normal development of the brain as well as in malignant primary brain tumors, gliomas, but the complete mechanism is still lacking. We decided to investigate the expression of the oncogenic miR-21 during normal mouse development and glioma, focusing on PDGF signaling as a potential regulator of miR-21. We generated mouse glioma using the RCAS/tv-a system for driving PDGF-BB expression in a cell-specific manner. Expression of miR-21 in mouse cell cultures and mouse brain were assessed using Northern blot analysis and in situ hybridization. Immunohistochemistry and Western blot analysis were used to investigate SOX2 expression. LNA-modified siRNA was used for irreversible depletion of miR-21. For inhibition of PDGF signaling Gleevec (imatinib mesylate), Rapamycin and U0126, as well as siRNA were used. Statistical significance was calculated using double-sided unpaired Student´s t-test. We identified miR-21 to be highly expressed during embryonic and newborn brain development followed by a gradual decrease until undetectable at postnatal day 7 (P7), this pattern correlated with SOX2 expression. Furthermore, miR-21 and SOX2 showed up-regulation and overlapping expression pattern in RCAS/tv-a generated mouse brain tumor specimens. Upon irreversible depletion of miR-21 the expression of SOX2 was strongly diminished in both mouse primary glioma cultures and human glioma cell lines. Interestingly, in normal fibroblasts the expression of miR-21 was induced by PDGF-BB, and inhibition of PDGF signaling in mouse glioma primary cultures resulted in suppression of miR-21 suggesting that mi

  11. Temporal expression of transporters and receptors in a rat primary co-culture blood-brain barrier model.

    Science.gov (United States)

    Liu, Houfu; Li, Yang; Lu, Sijie; Wu, Yiwen; Sahi, Jasminder

    2014-10-01

    1. The more relevant primary co-cultures of brain microvessel endothelial cells and astrocytes (BMEC) are less utilized for screening of potential CNS uptake when compared to intestinal and renal cell lines. 2. In this study, we characterized the temporal mRNA expression of major CNS transporters and receptors, including the transporter regulators Pxr, Ahr and Car in a rat BMEC co-cultured model. Permeability was compared with the Madin-Darby canine kidney (MDCKII)-MDR1 cell line and rat brain in situ perfusion model. 3. Our data demonstrated differential changes in expression of individual transporters and receptors over the culture period. Expression of ATP-binding cassette transporters was better retained than that of solute carrier transporters. The insulin receptor (IR) was best maintained among investigated receptors. AhR demonstrated high mRNA expression in rat brain capillaries and expression was better retained than Pxr or Car in culture. Mdr1b expression was up-regulated during primary culture, albeit Mdr1a mRNA levels were much higher. P-gp and Bcrp-1 were highly expressed and functional in this in vitro system. 4. Permeability measurements with 18 CNS marketed drugs demonstrated weak correlation between rBMEC model and rat in situ permeability and moderate correlation with MDCKII-MDR1 cells. 5. We have provided appropriate methodologies, as well as detailed and quantitative characterization data to facilitate improved understanding and rational use of this in vitro rat BBB model. PMID:24827375

  12. Correlation of aquaporin-4 expression to blood-brain barrier permeability in rats with focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pengcheng Xu; Haorong Feng; Jinbu Xu; Yongping Wu

    2008-01-01

    BACKGROUND: Ischemic cerebrovascular disease causes injury to the blood-brain barrier. The occurrence of brain edema is associated with aquaporin expression following cerebral ischemia/reperfusion. OBJECTIVE: To analyze the correlation of aquaporin-4 expression to brain edema and blood-brain barrier permeability in brain tissues of rat models of ischemia/reperfusion. DESIGN, TIME AND SETTING: The randomized control experiment was performed at the Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, China from December 2006 to October 2007. MATERIALS: A total of 112 adult, male, Sprague-Dawley rats, weighing 220-250 g, were used to establish rat models of middle cerebral artery occlusion and reperfusion by the suture method. Rabbit anti-aquaporin-4 (Santa Cruz, USA) and Evans blue (Sigma, USA) were used to analyze the tissue. METHODS: The rats were randomized into sham-operated (n = 16) and ischemia/reperfusion (n = 96) groups. There were 6 time points in the ischemia/reperfusion group, comprising 4, 6, 12, 24, 48, and 72 hours after reperfusion, with 16 rats for each time point. Rat models in the sham-operated group at 4 hours after surgery and rat models in the ischemia/reperfusion group at different time points were equally and randomly assigned into 4 different subgroups. MAIN OUTCOME MEASURES: Brain water content on the ischemic side and the control side was measured using the dry-wet weight method. Blood-brain barrier function was determined by Evans Blue. Aquaporin-4 expression surrounding the ischemic focus, as well as the correlation of aquaporin-4 expression with brain water content and Evans blue staining, were measured using immunohistochemistry and Western blot analysis. RESULTS: Brain water content on the ischemic side significantly increased at 12 hours after reperfusion, reached a peak at 48 hours, and was still high at 72 hours. Brain water content was greater on the ischemic hemispheres, compared with the control hemispheres

  13. Molecular cloning and expression analysis of fushi tarazu factor 1 in the brain of air-breathing catfish, Clarias gariepinus.

    Directory of Open Access Journals (Sweden)

    Parikipandla Sridevi

    Full Text Available BACKGROUND: Fushi tarazu factor 1 (FTZ-F1 encodes an orphan nuclear receptor belonging to the nuclear receptor family 5A (NR5A which includes adrenal 4-binding protein or steroidogenic factor-1 (Ad4BP/SF-1 and liver receptor homologue 1 (LRH-1 and plays a pivotal role in the regulation of aromatases. METHODOLOGY/PRINCIPAL FINDINGS: Present study was aimed to understand the importance of FTZ-F1 in relation to brain aromatase (cyp19a1b during development, recrudescence and after human chorionic gonadotropin (hCG induction. Initially, we cloned FTZ-F1 from the brain of air-breathing catfish, Clarias gariepinus through degenerate primer RT-PCR and RACE. Its sequence analysis revealed high homology with other NR5A1 group members Ad4BP/SF-1 and LRH-1, and also analogous to the spatial expression pattern of the latter. In order to draw functional correlation of cyp19a1b and FTZ-F1, we analyzed the expression pattern of the latter in brain during gonadal ontogeny, which revealed early expression during gonadal differentiation. The tissue distribution both at transcript and protein levels revealed its prominent expression in brain along with liver, kidney and testis. The expression pattern of brain FTZ-F1 during reproductive cycle and after hCG induction, in vivo was analogous to that of cyp19a1b shown in our earlier study indicating its involvement in recrudescence. CONCLUSIONS/SIGNIFICANCE: Based on our previous results on cyp19a1b and the present data, it is plausible to implicate potential roles for brain FTZ-F1 in ovarian differentiation and recrudescence process probably through regulation of cyp19a1b in teleosts. Nevertheless, these interactions would require primary coordinated response from ovarian aromatase and its related transcription factors.

  14. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

    Directory of Open Access Journals (Sweden)

    Yao Linli

    2013-02-01

    Full Text Available Abstract Background Hypoxia induces microglial activation which causes damage to the developing brain. Microglia derived inflammatory mediators may contribute to this process. Toll-like receptor 4 (TLR4 has been reported to induce microglial activation and cytokines production in brain injuries; however, its role in hypoxic injury remains uncertain. We investigate here TLR4 expression and its roles in neuroinflammation in neonatal rats following hypoxic injury. Methods One day old Wistar rats were subjected to hypoxia for 2 h. Primary cultured microglia and BV-2 cells were subjected to hypoxia for different durations. TLR4 expression in microglia was determined by RT-PCR, western blot and immunofluorescence staining. Small interfering RNA (siRNA transfection and antibody neutralization were employed to downregulate TLR4 in BV-2 and primary culture. mRNA and protein expression of tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β and inducible nitric oxide synthase (iNOS was assessed. Reactive oxygen species (ROS, nitric oxide (NO and NF-κB levels were determined by flow cytometry, colorimetric and ELISA assays respectively. Hypoxia-inducible factor-1 alpha (HIF-1α mRNA and protein expression was quantified and where necessary, the protein expression was depleted by antibody neutralization. In vivo inhibition of TLR4 with CLI-095 injection was carried out followed by investigation of inflammatory mediators expression via double immunofluorescence staining. Results TLR4 immunofluorescence and protein expression in the corpus callosum and cerebellum in neonatal microglia were markedly enhanced post-hypoxia. In vitro, TLR4 protein expression was significantly increased in both primary microglia and BV-2 cells post-hypoxia. TLR4 neutralization in primary cultured microglia attenuated the hypoxia-induced expression of TNF-α, IL-1β and iNOS. siRNA knockdown of TLR4 reduced hypoxia-induced upregulation of TNF-α, IL-1β, iNOS, ROS and

  15. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  16. Chronic Unpredictable Stress Decreases Expression of Brain-Derived Neurotrophic Factor (BDNF) in Mouse Ovaries: Relationship to Oocytes Developmental Potential

    OpenAIRE

    Li-Min Wu; Mei-Hong Hu; Xian-Hong Tong; Hui Han; Ni Shen; Ren-Tao Jin; Wei Wang; Gui-Xiang Zhou; Guo-Ping He; Yu-Sheng Liu

    2012-01-01

    BACKGROUND: Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chroni...

  17. Regulatable Gutless Adenovirus Vectors Sustain Inducible Transgene Expression in the Brain in the Presence of an Immune Response against Adenoviruses

    OpenAIRE

    Xiong, Weidong; Goverdhana, Shyam; Sciascia, Sandra A.; Candolfi, Marianela; Zirger, Jeffrey M.; BARCIA, CARLOS; Curtin, James F.; King, Gwendalyn D; Jaita, Gabriela; Liu, Chunyan; Kroeger, Kurt; Agadjanian, Hasmik; Medina-Kauwe, Lali; Palmer, Donna; Ng, Philip

    2006-01-01

    In view of recent serious adverse events and advances in gene therapy technologies, the use of regulatable expression systems is becoming recognized as indispensable adjuncts to successful clinical gene therapy. In the present work we optimized high-capacity adenoviral (HC-Ad) vectors encoding the novel tetracycline-dependent (TetOn)-regulatory elements for efficient and regulatable gene expression in the rat brain in vivo. We constructed two HC-Ad vectors encoding β-galactosidase (β-gal) dri...

  18. Gene Expression Analysis of Neurons and Astrocytes Isolated by Laser Capture Microdissection from Frozen Human Brain Tissues.

    Science.gov (United States)

    Tagliafierro, Lidia; Bonawitz, Kirsten; Glenn, Omolara C; Chiba-Falek, Ornit

    2016-01-01

    Different cell types and multiple cellular connections characterize the human brain. Gene expression analysis using a specific population of cells is more accurate than conducting analysis of the whole tissue homogenate, particularly in the context of neurodegenerative diseases, where a specific subset of cells is affected by the different pathology. Due to the difficulty of obtaining homogenous cell populations, gene expression in specific cell-types (neurons, astrocytes, etc.) has been understudied. To leverage the use of archive resources of frozen human brains in studies of neurodegenerative diseases, we developed and calibrated a method to quantify cell-type specific-neuronal, astrocytes-expression profiles of genes implicated in neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. Archive human frozen brain tissues were used to prepare slides for rapid immunostaining using cell-specific antibodies. The immunoreactive-cells were isolated by Laser Capture Microdissection (LCM). The enrichment for a particular cell-type of interest was validated in post-analysis stage by the expression of cell-specific markers. We optimized the technique to preserve the RNA integrity, so that the RNA was suitable for downstream expression analyses. Following RNA extraction, the expression levels were determined digitally using nCounter Single Cell Gene Expression assay (NanoString Technologies®). The results demonstrated that using our optimized technique we successfully isolated single neurons and astrocytes from human frozen brain tissues and obtained RNA of a good quality that was suitable for mRNA expression analysis. We present here new advancements compared to previous reported methods, which improve the method's feasibility and its applicability for a variety of downstream molecular analyses. Our new developed method can be implemented in genetic and functional genomic research of neurodegenerative diseases and has the potential to significantly

  19. Brain regions involved in processing facial identity and expression are differentially selective for surface and edge information

    OpenAIRE

    Harris, Richard J; Young, Andrew W; Andrews, Timothy J.

    2014-01-01

    Although different brain regions are widely considered to be involved in the recognition of facial identity and expression, it remains unclear how these regions process different properties of the visual image. Here, we ask how surface-based reflectance information and edge-based shape cues contribute to the perception and neural representation of facial identity and expression. Contrast-reversal was used to generate images in which normal contrast relationships across the surface of the imag...

  20. Quantitative proteomics reveals the novel co-expression signatures in early brain development for prognosis of glioblastoma multiforme

    OpenAIRE

    Yu, Xuexin; Feng, Lin; Liu, Dianming; Zhang, Lianfeng; Wu, Bo; Jiang, Wei; Han, Zujing; Cheng, Shujun

    2016-01-01

    Although several researches have explored the similarity across development and tumorigenesis in cellular behavior and underlying molecular mechanisms, not many have investigated the developmental characteristics at proteomic level and further extended to cancer clinical outcome. In this study, we used iTRAQ to quantify the protein expression changes during macaque rhesus brain development from fetuses at gestation 70 days to after born 5 years. Then, we performed weighted gene co-expression ...

  1. Ligula intestinalis infection is associated with alterations of both brain and gonad aromatase expression in roach (Rutilus rutilus).

    Science.gov (United States)

    Boulange-Lecomte, C; Geraudie, P; Forget-Leray, J; Gerbron, M; Minier, C

    2011-09-01

    The tapeworm Ligula intestinalis commonly infests roach (Rutilus rutilus) and is responsible for the inhibition of gonad development. In order to better understand the effect of the plerocercoid on fish physiology, and to discriminate parasitization effects from those of endocrine-disrupting compounds (EDC), Cyp19b and Cyp19a aromatase expression was investigated by real-time quantitative polymerase chain reaction (PCR) in brain and gonads of ligulosed roach, caught from a reference site. Data were compared to reproductive and endocrine endpoints previously reported in a larger cohort study (including the sampled population of the present one), such as gonadosomatic index, Fulton index, gonadal histology, plasma sex steroid levels and brain aromatase activity. A decrease in Cyp19b expression in the brain of infected fish was demonstrated, in agreement with the reduction of aromatase activity previously described. In contrast, Cyp19a expression in the gonads appeared to be enhanced in ligulosed fish, in accordance with the presence of immature but differentiated sexual tissues. Together these results show that: (1) L. intestinalis infestation results in an alteration of aromatase expression which, in particular, may have profound effects on the fish brain; and (2) L. intestinalis infection must be considered as a major confounding factor in ecotoxicological studies using aromatase expression as an EDC biomarker. Moreover, the concordance between activity and expression--investigated for the first time in the same population--gives a functional relevance to the transcript aromatase dosage in the brain. Finally, quantitative PCR was confirmed as a sensitive approach, enabling aromatase status to be defined in the poorly developed gonads of ligulosed individuals. PMID:21062527

  2. Gene expression patterns of spleen, lung and brain with different radiosensitivity in C57BL6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Majumder, Zahidur Rahman; Lee, Woo Jung; Bae, Sang Woo; Lee, Yun Sil [Laboratory of Radiation Effect, Seoul (Korea, Republic of); Lee, Su Jae [Laboratory of Radiation Experimental Therapeutics, Seoul (Korea, Republic of)

    2005-12-15

    Although little information is available on the underlying mechanisms, various genetic factors have been associated with tissue-specific responses to radiation. In the present study, we explored the possibility whether organ specific gene expression is associated with radiosensitivity using samples from brain, lung and spleen. We examined intrinsic expression pattern of 23 genes in the organs by semi-quantitative RT-PCR method using both male and female C57BL/6 mice. Expression of p53 and p21, well known factors for governing sensitivity to radiation or chemotherapeutic agents, was not different among the organ types. Both higher expression of sialyltransferase, delta7-sterol reductase, leptin receptor splice variant form 12.1, and Cu/Zn SuperOxide Dismutase (SOD) and lower expression of alphaB crystalline were specific for spleen tissue. Expression level of glutathione peroxidase and APO-1 cell surface antigen gene in lung tissue was high, while that of Na, K-ATPase alpha-subunit, Cu/ZnSOD, and cyclin G was low. Brain, radioresistant organ, showed higher expression of Na, K-ATPase-subunit, cyclin G, and nucleolar protein hNop56 and lower expression of delta7-sterol reductase. The result revealed a potential correlation between gene expression patterns and organ sensitivity, and identified genes which might be responsible for organ sensitivity.

  3. Synthesis of ino Acid Derived β-Cyclodextrins Used in Chiral Separation by Capillary Electrophoresis

    Institute of Scientific and Technical Information of China (English)

    戴荣继; 佟斌; 魏征; 顾峻岭; 邓玉林; 李明愉; 傅若农

    2004-01-01

    Six new kinds of ino acid derived β-cyclodextrins were synthesized to improve their water solubility and chiral separation properties. They are heptakis{2,6-di-O-[3-L-(1-isopropyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Val-β-CD), heptakis{2,6-di-O-[3-L-(1-benzyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Phe-β-CD), heptakis{2,6-di-O-[3-(D, L-1-benzyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. D,L-Phe-β-CD), heptakis{2,6-di-O-[3-(L-1-hydroxymethyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Ser-β-CD), heptakis{2,6-di-O-[3-(L-1-carboxylmethyl carboxyl methyl ino)- 2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Asp-β-CD), heptakis{2,6-di-O-[3-(L-2-carboxyl tetrethylene ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Pro-β-CD). Their chemical structures were certified using FTIR and 1H NMR. Except for L-Phe-β-CD and D,L-Phe-β-CD, that are in soluble in water, the other ino acid derived β-CDs all have good water solubility. D,L-tyrosine and promethazine were baselinely separated by L-Val-β-CD in capillary electrophoresis.

  4. Low-level laser therapy promotes dendrite growth via upregulating brain-derived neurotrophic factor expression

    Science.gov (United States)

    Meng, Chengbo; He, Zhiyong; Xing, Da

    2014-09-01

    Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via the increase of both BDNF mRNA and protein expression. In addition, dendrite growth was improved after LLLT, characterized by upregulation of PSD95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT can ameliorate Aβ-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Aβ-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of Alzheimer's disease.

  5. 3,4-methylenedioxyamphetamine upregulates p75 neurotrophin receptor protein expression in the rat brain

    Institute of Scientific and Technical Information of China (English)

    Chaomin Wang; Zugui Peng; Weihong Kuang; Hanyu Zheng; Jiang Long; Xue Wang

    2012-01-01

    The p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and following central nervous system injury. Previous stu-dies have shown that programmed cell death is likely involved in the neurotoxic effects of 3, 4-methylenedioxy-N-methylamphetamine (MDMA), because MDMA induces apoptosis of immor-talized neurons through regulation of proteins belonging to the Bcl-2 family. In the present study, intraperitoneal injection of different doses of MDMA (20, 50, and 100 mg/kg) induced significant behavioral changes, such as increased excitability, increased activity, and irritability in rats. Moreover, changes exhibited dose-dependent adaptation. Following MDMA injection in rat brain tissue, the number of apoptotic cells dose-dependently increased and p75 neurotrophin receptor expression significantly increased in the prefrontal cortex, cerebellum, and hippocampus. These findings confirmed that MDMA induced neuronal apoptosis, and results suggested that this effect was related by upregulated protein expression of the p75 neurotrophin receptor.

  6. Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

    Science.gov (United States)

    Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

    2002-12-30

    Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity. PMID:12531529

  7. 3,4-methylenedioxyamphetamine upregulates p75 neurotrophin receptor protein expression in the rat brain.

    Science.gov (United States)

    Wang, Chaomin; Peng, Zugui; Kuang, Weihong; Zheng, Hanyu; Long, Jiang; Wang, Xue

    2012-04-25

    The p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and following central nervous system injury. Previous studies have shown that programmed cell death is likely involved in the neurotoxic effects of 3, 4-methylenedioxy-N-methylamphetamine (MDMA), because MDMA induces apoptosis of immortalized neurons through regulation of proteins belonging to the Bcl-2 family. In the present study, intraperitoneal injection of different doses of MDMA (20, 50, and 100 mg/kg) induced significant behavioral changes, such as increased excitability, increased activity, and irritability in rats. Moreover, changes exhibited dose-dependent adaptation. Following MDMA injection in rat brain tissue, the number of apoptotic cells dose-dependently increased and p75 neurotrophin receptor expression significantly increased in the prefrontal cortex, cerebellum, and hippocampus. These findings confirmed that MDMA induced neuronal apoptosis, and results suggested that this effect was related by upregulated protein expression of the p75 neurotrophin receptor. PMID:25722682

  8. DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katherine E. Horn

    2013-01-01

    Full Text Available The transmembrane protein deleted in colorectal cancer (DCC and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP, intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.

  9. Expression and cellular function of vSNARE proteins in brain astrocytes.

    Science.gov (United States)

    Ropert, N; Jalil, A; Li, D

    2016-05-26

    Gray matter protoplasmic astrocytes, a major type of glial cell in the mammalian brain, extend thin processes ensheathing neuronal synaptic terminals. Albeit electrically silent, astrocytes respond to neuronal activity with Ca(2+) signals that trigger the release of gliotransmitters, such as glutamate, d-serine, and ATP, which modulate synaptic transmission. It has been suggested that the astrocytic processes, together with neuronal pre- and post-synaptic elements, constitute a tripartite synapse, and that astrocytes actively regulate information processing. Astrocytic vesicles expressing VAMP2 and VAMP3 vesicular SNARE (vSNARE) proteins have been suggested to be a key feature of the tripartite synapse and mediate gliotransmitter release through Ca(2+)-regulated exocytosis. However, the concept of exocytotic release of gliotransmitters by astrocytes has been challenged. Here we review studies investigating the expression profile of VAMP2 and VAMP3 vSNARE proteins in rodent astrocytes, and the functional implication of VAMP2/VAMP3 vesicles in astrocyte signaling. We also discuss our recent data suggesting that astrocytic VAMP3 vesicles regulate the trafficking of glutamate transporters at the plasma membrane and glutamate uptake. A better understanding of the functional consequences of the astrocytic vSNARE vesicles on glutamate signaling, neuronal excitability and plasticity, will require the development of new strategies to selectively interrogate the astrocytic vesicles trafficking in vivo. PMID:26518463

  10. Influence of X-rays on early response gene expression in rat astrocytes and brain tumour cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Vrdoljak, E.; Borchardt, P.E.; Bill, C.A.; Stephens, L.C.; Tofilon, P.J. [Anderson (M.D.) Cancer Center, Houston, TX (United States)

    1994-12-01

    The effects of ionizing radiation on c-fos, c-jun and jun-B mRNA levels were determined in cultures of rat perinatal type 1 astrocytes and two rat brain tumour cell lines, 175A and 9L. In astrocyte cultures X-ray doses as low as 1 Gy induced the expression of c-fos and jun-B but had essentially no effect on c-jun. The maximum increase in expression was found 1 h after irradiation, which then rapidly returned to control levels. These findings suggest that astrocytes may play a role in mediating the radiation response of the central nervous system via X-ray-induced changes in gene expression. In contrast, doses of up to 20 Gy had no effect on c-fos, c-jun and jun-B mRNA levels in the two brain tumour cell lines. In addition, whereas 12-0-tetradecanoylphorbol-13-acetate induced the expression of these genes in astrocytes, it had little or no effect on fos or jun expression in 9L or 175A cells. These results suggest that the signal transduction pathways mediating radiation-induced genes expression may be different in normal astrocytes and brain tumour cells. (author).

  11. Quantitative proteomics reveals the novel co-expression signatures in early brain development for prognosis of glioblastoma multiforme.

    Science.gov (United States)

    Yu, Xuexin; Feng, Lin; Liu, Dianming; Zhang, Lianfeng; Wu, Bo; Jiang, Wei; Han, Zujing; Cheng, Shujun

    2016-03-22

    Although several researches have explored the similarity across development and tumorigenesis in cellular behavior and underlying molecular mechanisms, not many have investigated the developmental characteristics at proteomic level and further extended to cancer clinical outcome. In this study, we used iTRAQ to quantify the protein expression changes during macaque rhesus brain development from fetuses at gestation 70 days to after born 5 years. Then, we performed weighted gene co-expression network analysis (WGCNA) on protein expression data of brain development to identify co-expressed modules that highly expressed on distinct development stages, including early stage, middle stage and late stage. Moreover, we used the univariate cox regression model to evaluate the prognostic potentials of these genes in two independent glioblastoma multiforme (GBM) datasets. The results showed that the modules highly expressed on early stage contained more reproducible prognostic genes, including ILF2, CCT7, CCT4, RPL10A, MSN, PRPS1, TFRC and APEX1. These genes were not only associated with clinical outcome, but also tended to influence chemoresponse. These signatures identified from embryonic brain development might contribute to precise prediction of GBM prognosis and identification of novel drug targets in GBM therapies. Thus, the development could become a viable reference model for researching cancers, including identifying novel prognostic markers and promoting new therapies. PMID:26895104

  12. Influence of X-rays on early response gene expression in rat astrocytes and brain tumour cell lines

    International Nuclear Information System (INIS)

    The effects of ionizing radiation on c-fos, c-jun and jun-B mRNA levels were determined in cultures of rat perinatal type 1 astrocytes and two rat brain tumour cell lines, 175A and 9L. In astrocyte cultures X-ray doses as low as 1 Gy induced the expression of c-fos and jun-B but had essentially no effect on c-jun. The maximum increase in expression was found 1 h after irradiation, which then rapidly returned to control levels. These findings suggest that astrocytes may play a role in mediating the radiation response of the central nervous system via X-ray-induced changes in gene expression. In contrast, doses of up to 20 Gy had no effect on c-fos, c-jun and jun-B mRNA levels in the two brain tumour cell lines. In addition, whereas 12-0-tetradecanoylphorbol-13-acetate induced the expression of these genes in astrocytes, it had little or no effect on fos or jun expression in 9L or 175A cells. These results suggest that the signal transduction pathways mediating radiation-induced genes expression may be different in normal astrocytes and brain tumour cells. (author)

  13. Chemotherapy Modulates Intestinal Immune Gene Expression Including Surfactant Protein-D and Deleted in Malignant Brain Tumors 1 in Piglets

    DEFF Research Database (Denmark)

    Rathe, Mathias; Thomassen, Mads; Shen, René L.; Pontoppidan, Peter E L; Husby, Steffen; Müller, Klaus; Kruse, Torben A.; Sangild, Per T.

    BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among...

  14. Shared Pathways Among Autism Candidate Genes Determined by Co-expression Network Analysis of the Developing Human Brain Transcriptome.

    Science.gov (United States)

    Mahfouz, Ahmed; Ziats, Mark N; Rennert, Owen M; Lelieveldt, Boudewijn P F; Reinders, Marcel J T

    2015-12-01

    Autism spectrum disorder (ASD) is a neurodevelopmental syndrome known to have a significant but complex genetic etiology. Hundreds of diverse genes have been implicated in ASD; yet understanding how many genes, each with disparate function, can all be linked to a single clinical phenotype remains unclear. We hypothesized that understanding functional relationships between autism candidate genes during normal human brain development may provide convergent mechanistic insight into the genetic heterogeneity of ASD. We analyzed the co-expression relationships of 455 genes previously implicated in autism using the BrainSpan human transcriptome database, across 16 anatomical brain regions spanning prenatal life through adulthood. We discovered modules of ASD candidate genes with biologically relevant temporal co-expression dynamics, which were enriched for functional ontologies related to synaptogenesis, apoptosis, and GABA-ergic neurons. Furthermore, we also constructed co-expression networks from the entire transcriptome and found that ASD candidate genes were enriched in modules related to mitochondrial function, protein translation, and ubiquitination. Hub genes central to these ASD-enriched modules were further identified, and their functions supported these ontological findings. Overall, our multi-dimensional co-expression analysis of ASD candidate genes in the normal developing human brain suggests the heterogeneous set of ASD candidates share transcriptional networks related to synapse formation and elimination, protein turnover, and mitochondrial function. PMID:26399424

  15. Brain-Derived Neurotrophic Factor Gene Expression in Pediatric Bipolar Disorder: Effects of Treatment and Clinical Response

    Science.gov (United States)

    Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Dwivedi, Yogesh; Pavuluri, Mani N.

    2008-01-01

    The study determines the gene expression of brain-derived neurotrophic factor (BDNF) in the lymphocytes of subjects with pediatric bipolar disorder (PBD) before and during treatment with mood stabilizers and in drug-free normal control subjects. Results indicate the potential of BDNF levels as a biomarker for PBD and as a treatment predictor and…

  16. Mushroom Bodies of the Honeybee Brain Show Cell Population-Specific Plasticity in Expression of Amine-Receptor Genes

    Science.gov (United States)

    McQuillan, H. James; Nakagawa, Shinichi; Mercer, Alison R.

    2012-01-01

    Dopamine and octopamine released in the mushroom bodies of the insect brain play a critical role in the formation of aversive and appetitive memories, respectively. As recent evidence suggests a complex relationship between the effects of these two amines on the output of mushroom body circuits, we compared the expression of dopamine- and…

  17. Astaxanthin reduces matrix metalloproteinase-9 expression and activity in the brain after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Zhang, Xiang-Sheng; Zhang, Xin; Zhang, Qing-Rong; Wu, Qi; Li, Wei; Jiang, Tian-Wei; Hang, Chun-Hua

    2015-10-22

    We have previously shown that astaxanthin (ATX) reduces the blood-brain barrier (BBB) disruption and neurovascular dysfunction following subarachnoid hemorrhage (SAH) insults. However, the underlying mechanisms remain unclear. It is known that the matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9 (MMP-9) plays a crucial role in the pathogenesis of secondary brain injury after SAH. And ATX has the ability to regulate MMP-9 in other models. Herein, we investigated whether ATX could ameliorate MMP-9 activation and expression in a rat model of SAH. A total of 144 rats were randomly divided into the following groups: control group (n=36), SAH group (n=36), SAH+vehicle group (n=36), and SAH+ATX group (n=36). The SAH model was induced by injection of 0.3 ml autologous blood into the prechiasmatic cistern. ATX (20 μl of 0.1 mmol) or vehicle was administered intracerebroventricularly 30 min after SAH induction. Mortality, neurological function, brain edema and blood-brain barrier (BBB) permeability were measured at 24 and 72 h after SAH. Biochemical and zymographic methods were used to analyze MMP-9 expression and activity in brain samples. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were also evaluated at 24h. Our data indicated that ATX could significantly reduce the expression and activity of MMP-9, leading to the amelioration of brain edema, BBB impairment, neurological deficits and TUNEL-positive cells at 24h but not 72 h after SAH. The ATX-mediated down-regulation of MMP-9 was correlated with the decreased levels of IL-1β, TNF-α, oxidative stress, activated microglia and infiltrating neutrophils. These results suggest that the neurovascular protection of ATX in SAH is partly associated with the inhibition of MMP-9 expression and activity. PMID:26210617

  18. Treadmill exercise ameliorates ischemia-induced brain edema while suppressing Na⁺/H⁺ exchanger 1 expression.

    Science.gov (United States)

    Nishioka, Ryutaro; Sugimoto, Kana; Aono, Hitomi; Mise, Ayano; Choudhury, Mohammed E; Miyanishi, Kazuya; Islam, Afsana; Fujita, Takahiro; Takeda, Haruna; Takahashi, Hisaaki; Yano, Hajime; Tanaka, Junya

    2016-03-01

    Exercise may be one of the most effective and sound therapies for stroke; however, the mechanisms underlying the curative effects remain unclear. In this study, the effects of forced treadmill exercise with electric shock on ischemic brain edema were investigated. Wistar rats were subjected to transient (90 min) middle cerebral artery occlusion (tMCAO). Eighty nine rats with substantially large ischemic lesions were evaluated using magnetic resonance imaging (MRI) and were randomly assigned to exercise and non-exercise groups. The rats were forced to run at 4-6m/s for 10 min/day on days 2, 3 and 4. Brain edema was measured on day 5 by MRI, histochemical staining of brain sections and tissue water content determination (n=7, each experiment). Motor function in some rats was examined on day 30 (n=6). Exercise reduced brain edema (Pexercise. Exercise prevented the ischemia-induced expression of mRNA encoding aquaporin 4 (AQP4) and Na(+)/H(+) exchangers (NHEs) (n=5 or 7, Prat brains and also in mixed glial cultures. Corticosterone at ~10nM reduced NHE1 and AQP4 expression in mixed glial and pure microglial cultures. Dexamethasone and aldosterone at 10nM did not significantly alter NHE1 and AQP4 expression. Exposure to a NHE inhibitor caused shrinkage of microglial cells. These results suggest that the stressful short-period and slow-paced treadmill exercise suppressed NHE1 and AQP4 expression resulting in the amelioration of brain edema at least partly via the moderate increase in plasma corticosterone levels. PMID:26724742

  19. A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and interaction

    Directory of Open Access Journals (Sweden)

    Århem Peter

    2005-11-01

    Full Text Available Abstract Background The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice. Results We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER. Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons. Conclusion The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth.

  20. Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor

    Directory of Open Access Journals (Sweden)

    d'Avila Joana C

    2012-02-01

    Full Text Available Abstract Background Traumatic brain injury (TBI induces activation of microglia. Activated microglia can in turn increase secondary injury and impair recovery. This innate immune response requires hours to days to become fully manifest, thus providing a clinically relevant window of opportunity for therapeutic intervention. Microglial activation is regulated in part by poly(ADP-ribose polymerase-1 (PARP-1. Inhibition of PARP-1 activity suppresses NF-kB-dependent gene transcription and thereby blocks several aspects of microglial activation. Here we evaluated the efficacy of a PARP inhibitor, INO-1001, in suppressing microglial activation after cortical impact in the rat. Methods Rats were subjected to controlled cortical impact and subsequently treated with 10 mg/kg of INO-1001 (or vehicle alone beginning 20 - 24 hours after the TBI. Brains were harvested at several time points for histological evaluation of inflammation and neuronal survival, using markers for microglial activation (morphology and CD11b expression, astrocyte activation (GFAP, and neuronal survival (NeuN. Rats were also evaluated at 8 weeks after TBI using measures of forelimb dexterity: the sticky tape test, cylinder test, and vermicelli test. Results Peak microglial and astrocyte activation was observed 5 to 7 days after this injury. INO-1001 significantly reduced microglial activation in the peri-lesion cortex and ipsilateral hippocampus. No rebound inflammation was observed in rats that were treated with INO-1001 or vehicle for 12 days followed by 4 days without drug. The reduced inflammation was associated with increased neuronal survival in the peri-lesion cortex and improved performance on tests of forelimb dexterity conducted 8 weeks after TBI. Conclusions Treatment with a PARP inhibitor for 12 days after TBI, with the first dose given as long as 20 hours after injury, can reduce inflammation and improve histological and functional outcomes.

  1. Intoxicação experimental por monensina em eqüinos

    OpenAIRE

    Bezerra Jr Pedro Soares; Ilha Marcia Regina Silva; Langohr Ingeborg Maria; Barros Claudio S. L.

    2000-01-01

    Sete eqüinos foram tratados experimentalmente com monensina sódica. Dois desses animais receberem 3-4 kg/eqüino/dia de uma ração comercial sabidamente implicada em surtos naturais da intoxicação por monensina em eqüinos e que continha 180 ppm±20 da droga. Um eqüino recebeu uma única dose de 5 mg/kg e um outro recebeu 4 doses diárias de 1 mg/kg de monensina sódica originária de um premix. Esses quatro eqüinos morreram ou foram sacrificados in extremis, 3-8 dias após o início da administração d...

  2. Astrocyte-targeted expression of interleukin-3 and interferon-alpha causes region-specific changes in metallothionein expression in the brain

    DEFF Research Database (Denmark)

    Giralt, M; Carrasco, J; Penkowa, M; Morcillo, M A; Santamaría, J; Campbell, I L; Hidalgo, J

    2001-01-01

    Purkinje and granular layers of the cerebellum, as well as in its white matter tracts. In contrast to the cerebellum and brain stem, MT-I+II were downregulated by IL-3 in the hippocampus and the remaining brain in the older mice. In situ hybridization for MT-III RNA revealed a modest increase in the......Transgenic mice expressing IL-3 and IFN-alpha under the regulatory control of the GFAP gene promoter (GFAP-IL3 and GFAP-IFNalpha mice) exhibit a cytokine-specific, late-onset chronic-progressive neurological disorder which resemble many of the features of human diseases such as multiple sclerosis...

  3. Effect of montelukast on the expression of interleukin-18, telomerase reverse transcriptase, and Bcl-2 in the brain tissue of neonatal rats with hypoxic-ischemic brain damage.

    Science.gov (United States)

    Liu, J L; Zhao, X H; Zhang, D L; Zhang, J B; Liu, Z H

    2015-01-01

    The aim of this study was to investigate the effect of montelukast on the expression of interleukin (IL)-18, telomerase reverse transcriptase (TERT), and Bcl-2 in the brain tissue of neonatal rats with hypox-ic-ischemic brain damage (HIBD). To establish the model of HIBD, 8% oxygen was applied to rats after the unilateral carotid artery was ligated. Twenty rats were randomly assigned to the control group, while another 40 were used to establish the HIBD model and were randomly divided equally into model group and treatment group. A 0.1 mg/kg dose of montelukast or an equal volume of saline was intraperitoneally injected to the rats in the treatment group and the model group, respectively. Brain tissue from 4 rats in each group was sampled at 0, 6, 12, 24, and 72 h after brain damage, and immunohistochemistry was used to measure IL-18, TERT and Bcl-2 expressions. IL-18, TERT, and Bcl-2 levels increased after 12 h in both the model group and treatment group, peaked after 48 h, and then decreased. Although not statistically significant, IL-18, TERT, and Bcl-2 expressions after 24, 48, and 96 h were all lower in the treatment group than those in the model group. In conclusion, montelukast has a protective effect on the cerebral tissue of neonatal rats with HIBD, and may mediate an increase of TERT and Bcl-2 levels but not of IL-18. Further study is required to elucidate the mechanism of the protective effect of montelukast on HIBD. PMID:26345821

  4. Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

    OpenAIRE

    Davor Stanić; Sydney Dubois; Hui Kheng Chua; Bruce Tonge; Nicole Rinehart; Malcolm K Horne; Wah Chin Boon

    2014-01-01

    Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, in...

  5. Monocrotophos induces the expression and activity of xenobiotic metabolizing enzymes in pre-sensitized cultured human brain cells.

    Directory of Open Access Journals (Sweden)

    Vinay K Tripathi

    Full Text Available The expression and metabolic profile of cytochrome P450s (CYPs is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y and glial (U373-MG cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC, cyclophosphamide (CPA, ethanol and known neurotoxicant- monocrotophos (MCP, a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against

  6. Roles of apolipoprotein E (ApoE and inducible nitric oxide synthase (iNOS in inflammation and apoptosis in preeclampsia pathogenesis and progression.

    Directory of Open Access Journals (Sweden)

    Luyi Mao

    Full Text Available OBJECTIVES: To investigate potential roles of inducible nitric oxide synthase (iNOS and apolipoprotein (apoE in inflammation and apoptosis promoting pathological changes in preeclampsia in pregnant mice with apoE and/or iNOS knock out. METHODS: B6.129 mice were crossed to produce WT, apoE(-/-, apoE(+/-, iNOS(-/-, iNOS(+/- and apoE(-/-iNOS(-/- groups. Variants were confirmed by PCR. Serum lipid parameters (triglycerides, TG; total cholesterol, TC; high density lipoprotein, HDL; and low density lipoprotein, LDL, NO levels and placental electronic microscopic ultrastructures were evaluated, and blood pressure (BP, 24-hour urine protein and pregnancy outcomes were recorded for pregnant F1 generation mice. Placental expressions of inflammatory (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; nuclear factor-κB, NF-κb and apoptotic markers (Bcl-2 associated X protein, Bax, B-cell lymphoma/leukemia-2, Bcl-2, and Caspase-3 were evaluated via Western blot. RESULTS: Serum lipids, BP and 24-hour urine protein levels were shown to be significantly higher and parturition and placenta weights were lower in apoE(-/- and apoE(-/-iNOS(-/- groups (p0.05 showed no differences. In addition, placenta vascular endothelial and trophoblast cell morphological changes were demonstrated in both the apoE(-/-iNOS(-/- and apoE(-/- groups. CONCLUSION: Elevated lipid metabolism and inflammatory/apoptosis parameters suggest a potentially significant role of apoE in preeclampsia pathology, as well as a relationship between iNOS and preeclampsia progression.

  7. Human brain endothelial cells endeavor to immunoregulate CD8 T cells via PD-1 ligand expression in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Pittet Camille L

    2011-11-01

    Full Text Available Abstract Background Multiple sclerosis (MS, an inflammatory disease of the central nervous system (CNS, is characterized by blood-brain barrier (BBB disruption and massive infiltration of activated immune cells. Engagement of programmed cell death-1 (PD-1 expressed on activated T cells with its ligands (PD-L1 and PD-L2 suppresses T cell responses. We recently demonstrated in MS lesions elevated PD-L1 expression by glial cells and absence of PD-1 on many infiltrating CD8 T cells. We have now investigated whether human brain endothelial cells (HBECs, which maintain the BBB, can express PD-L1 or PD-L2 and thereby modulate T cells. Methods We used primary cultures of HBECs isolated from non-tumoral CNS tissue either under basal or inflamed conditions. We assessed the expression of PD-L1 and PD-L2 using qPCR and flow cytometry. Human CD8 T cells were isolated from peripheral blood of healthy donors and co-cultured with HBECs. Following co-culture with HBECs, proliferation and cytokine production by human CD8 T cells were measured by flow cytometry whereas transmigration was determined using a well established in vitro model of the BBB. The functional impact of PD-L1 and PD-L2 provided by HBECs was determined using blocking antibodies. We performed immunohistochemistry for the detection of PD-L1 or PD-L2 concurrently with caveolin-1 (a cell specific marker for endothelial cells on post-mortem human brain tissues obtained from MS patients and normal controls. Results Under basal culture conditions, PD-L2 is expressed on HBECs, whilst PD-L1 is not detected. Both ligands are up-regulated under inflammatory conditions. Blocking PD-L1 and PD-L2 leads to increased transmigration and enhanced responses by human CD8 T cells in co-culture assays. Similarly, PD-L1 and PD-L2 blockade significantly increases CD4 T cell transmigration. Brain endothelium in normal tissues and MS lesions does not express detectable PD-L1; in contrast, all blood vessels in normal

  8. Sex chromosome complement determines sex differences in aromatase expression and regulation in the stria terminalis and anterior amygdala of the developing mouse brain.

    Science.gov (United States)

    Cisternas, Carla D; Tome, Karina; Caeiro, Ximena E; Dadam, Florencia M; Garcia-Segura, Luis M; Cambiasso, María J

    2015-10-15

    Aromatase, which converts testosterone in estradiol, is involved in the generation of brain sex dimorphisms. Here we used the "four core genotypes" mouse model, in which the effect of gonadal sex and sex chromosome complement is dissociated, to determine if sex chromosomes influence the expression of brain aromatase. The brain of 16 days old XY mouse embryos showed higher aromatase expression in the stria terminalis and the anterior amygdaloid area than the brain of XX embryos, independent of gonadal sex. Furthermore, estradiol or dihydrotestosterone increased aromatase expression in cultures of anterior amygdala neurons derived from XX embryos, but not in those derived from XY embryos. This effect was also independent of gonadal sex. The expression of other steroidogenic molecules, estrogen receptor-α and androgen receptor was not influenced by sex chromosomes. In conclusion, sex chromosomes determine sex dimorphisms in aromatase expression and regulation in the developing mouse brain. PMID:26231585

  9. Identification, tissue distribution and evaluation of brain neuropeptide Y gene expression in the Brazilian flounder Paralichthys orbignyanus

    Indian Academy of Sciences (India)

    Vinicius F Campos; Tiago Collares; João C Deschamps; Fabiana K Seixas; Odir A Dellagostin; Carlos Frederico C Lanes; Juliana Sandrini; Luis Fernando Marins; Marcelo Okamoto; Luís A Sampaio; Ricardo B Robaldo

    2010-09-01

    Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in vertebrates, mammals and fish. However, the present knowledge about feeding behaviour in fish is still limited and based on studies in a few species. The Brazilian flounder Paralichthys orbignyanus is being considered for aquaculture, and it is important to understand the mechanisms regulating feeding in order to improve its performance in captivity. The objectives of this study were to clone NPY cDNA, evaluate the mRNA levels in different tissues of flounder, and also evaluate brain NPY expression to associate food intake with NPY expression levels. A 597 bp NPY cDNA was cloned from Brazilian flounder brain. NPY expression was detected in all the peripheral tissues analysed. No significant differences were observed in brain NPY gene expression over 24 h after food intake at a temperature of 15 ± 3°C. No correlation was observed among plasma glucose, total protein, cholesterol, triglycerides and NPY expression levels during this 24 h period. On the other hand, mRNA levels were increased after two weeks of fasting at elevated temperatures. Our results suggest that NPY mRNA levels in Brazilian flounder are affected by temperature.

  10. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites

    Energy Technology Data Exchange (ETDEWEB)

    Cordon-Cardo, C.; O' Brien, J.P.; Casals, D.; Biedler, J.L.; Melamed, M.R.; Bertino, J.R. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA)); Rittman-Grauer, L. (Hybritech, Inc., San Diego, CA (USA))

    1989-01-01

    Endothelial cells of human capillary blood vessels at the blood-brain and other blood-tissue barrier sites express P-glycoprotein as detected by mouse monoclonal antibodies against the human multidrug-resistance gene product. This pattern of endothelial cell expression may indicate a physiological role for P-glycoprotein in regulating the entry of certain molecules into the central nervous system and other anatomic compartments, such as the testes. These tissues, which limit the access of systemic drugs, are known pharmacologic sanctuaries for metastatic cancer. P-glycoprotein expression in capillary endothelium of brain and testes and not other tissues (i.e., kidney and placenta) may in part explain this phenomenon and could have important implications in cancer chemotherapy.

  11. Changes in neurotransmitter levels and expression of immediate early genes in brain of mice infected with Neospora caninum

    Science.gov (United States)

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Furuoka, Hidefumi; Yokoyama, Naoaki; Nishikawa, Yoshifumi

    2016-01-01

    Neospora caninum is an obligate intracellular parasite that causes neurological disorders in dogs and cattle. The majority of host animals are asymptomatic at the chronic stage of infection. However, it remains unclear whether cerebral function is normal in asymptomatic animals. In this study, mice were infected with N. caninum (strain Nc-1) and their brains were examined to understand changes in cerebral function at the chronic stage of infection. Mice infected with N. caninum showed impaired locomotor activity, but no differences in clinical symptoms were observed. In the brains of infected mice, parasites were distributed throughout the brain and histological lesions were observed everywhere except for the cerebellum. Expression levels of proinflammatory cytokines, interferon-gamma and tumour necrosis factor-alpha, were highly upregulated in several brain regions of infected mice. Additionally, the level of neurotransmitters glutamate, glycine, gamma-aminobutyric acid, dopamine and 5-hydroxytryptamine, were altered in infected mice compared with those of uninfected mice. Interestingly, the expression levels of immediately early genes, c-Fos and Arc, in the brain of infected mice were lower than those of in uninfected mice. Our findings may provide insight into neurological disorders associated with N. caninum infection. PMID:26971577

  12. Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1.

    Science.gov (United States)

    Dawson, N; Kurihara, M; Thomson, D M; Winchester, C L; McVie, A; Hedde, J R; Randall, A D; Shen, S; Seymour, P A; Hughes, Z A; Dunlop, J; Brown, J T; Brandon, N J; Morris, B J; Pratt, J A

    2015-01-01

    Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity. PMID:25989143

  13. Opiates Upregulate Adhesion Molecule Expression in Brain MicroVascular Endothelial Cells (BMVEC: Implications for Altered Blood Brain Barrier (BBB Permeability

    Directory of Open Access Journals (Sweden)

    Madhavan P.N. Nair

    2006-01-01

    Full Text Available The blood-brain barrier (BBB is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of immunocompetent cells into the central nervous system (CNS. Expression of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 on brain microvascular endothelial cells (BMVEC and their interaction with human immunodeficiency virus (HIV-1 viral proteins may help enhance viral adhesion and virus-cell fusion resulting in increased infectivity. Additionally, transmigration through the BBB is facilitated by both endothelial and monocyte/macrophage-derived nitric oxide (NO. Dysregulated production of NO by BMVEC due to opiates and HIV-1 viral protein interactions play a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB. Opioids act as co-factors in the neuropathogenesis of HIV-1 by facilitating BBB dysfunction however, no studies have been done to investigate the role of opiates alone or in combination with HIV-1 viral proteins on adhesion molecule expression in BMVEC. We hypothesize that opiates such as heroin and morphine in conjunction with the HIV-1 viral protein gp120 increase the expression of adhesion molecules ICAM-1 and VCAM-1 and these effects are mediated via the modulation of NO. Results show that opiates alone and in synergy with gp120 increase both the genotypic and phenotypic expression of ICAM-1 and VCAM-1 by BMVEC, additionally, these opiate induced effects may be the result of increased NO production. These studies will provide a better understanding of how opiate abuse in conjunction with HIV-1 infection facilitates the breakdown of the BBB and exacerbates the neuropathogenesis of HIV-1. Elucidation of the mechanisms of BBB modulation will provide new therapeutic approaches to maintain BBB integrity

  14. Exploring the motivational brain: effects of implicit power motivation on brain activation in response to facial expressions of emotion

    OpenAIRE

    Schultheiss, Oliver C.; Wirth, Michelle M.; WAUGH, CHRISTIAN E.; Stanton, Steven J.; Meier, Elizabeth A.; Reuter-Lorenz, Patricia

    2008-01-01

    This study tested the hypothesis that implicit power motivation (nPower), in interaction with power incentives, influences activation of brain systems mediating motivation. Twelve individuals low (lowest quartile) and 12 individuals high (highest quartile) in nPower, as assessed per content coding of picture stories, were selected from a larger initial participant pool and participated in a functional magnetic resonance imaging study during which they viewed high-dominance (angry faces), low-...

  15. Tooth pulp inflammation increases brain-derived neurotrophic factor expression in rodent trigeminal ganglion neurons.

    Science.gov (United States)

    Tarsa, L; Bałkowiec-Iskra, E; Kratochvil, F J; Jenkins, V K; McLean, A; Brown, A L; Smith, J A; Baumgartner, J C; Balkowiec, A

    2010-06-01

    Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by electrical stimulation and calcitonin gene-related peptide (CGRP), a well-established mediator of trigeminal inflammatory pain. These data suggest that BDNF plays a role in activity-dependent plasticity at first-order trigeminal synapses, including functional changes that take place in trigeminal nociceptive pathways during chronic inflammation. The present study was designed to determine the effects of peripheral inflammation, using tooth pulp inflammation as a model, on regulation of BDNF expression in TG neurons of juvenile rats and mice. Cavities were prepared in right-side maxillary first and second molars of 4-week-old animals, and left open to oral microflora. BDNF expression in right TG was compared with contralateral TG of the same animal, and with right TG of sham-operated controls, 7 and 28 days after cavity preparation. Our ELISA data indicate that exposing the tooth pulp for 28 days, with confirmed inflammation, leads to a significant upregulation of BDNF in the TG ipsilateral to the affected teeth. Double-immunohistochemistry with antibodies against BDNF combined with one of nociceptor markers, CGRP or transient receptor potential vanilloid type 1 (TRPV1), revealed that BDNF is significantly upregulated in TRPV1-immunoreactive (IR) neurons in both rats and mice, and CGRP-IR neurons in mice, but not rats. Overall, the inflammation-induced upregulation of BDNF is stronger in mice

  16. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation

    Directory of Open Access Journals (Sweden)

    Soliman Mahmoud L

    2012-03-01

    Full Text Available Abstract Background Long-term acetate supplementation reduces neuroglial activation and cholinergic cell loss in a rat model of lipopolysaccharide-induced neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to induce acetate supplementation, increases histone H3 and H4 acetylation and inhibits histone deacetylase activity and histone deacetylase-2 expression in normal rat brain. Here, we propose that the therapeutic effect of acetate in reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced changes in histone acetylation and pro-inflammatory cytokine expression. Methods In this study, we examined the effect of a 28-day-dosing regimen of glyceryl triacetate, to induce acetate supplementation, on brain histone acetylation and interleukin-1β expression in a rat model of lipopolysaccharide-induced neuroinflammation. The effect was analyzed using Western blot analysis, quantitative real-time polymerase chain reaction and enzymic histone deacetylase and histone acetyltransferase assays. Statistical analysis was performed using one-way analysis of variance, parametric or nonparametric when appropriate, followed by Tukey's or Dunn's post-hoc test, respectively. Results We found that long-term acetate supplementation increased the proportion of brain histone H3 acetylated at lysine 9 (H3K9, histone H4 acetylated at lysine 8 and histone H4 acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate, long-term treatment increased histone acetyltransferase activity and had no effect on histone deacetylase activity, with variable effects on brain histone deacetylase class I and II expression. In agreement with this hypothesis, neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which was effectively reversed with acetate supplementation. Further, in rats subjected to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine interleukin-1β protein

  17. Ganglioside metabolism in a transgenic mouse model of Alzheimer's disease: expression of Chol-1α antigens in the brain

    Directory of Open Access Journals (Sweden)

    Toshio Ariga

    2010-10-01

    Full Text Available The accumulation of Aβ (amyloid β-protein is one of the major pathological hallmarks in AD (Alzheimer's disease. Gangliosides, sialic acid-containing glycosphingolipids enriched in the nervous system and frequently used as biomarkers associated with the biochemical pathology of neurological disorders, have been suggested to be involved in the initial aggregation of Aβ. In the present study, we have examined ganglioside metabolism in the brain of a double-Tg (transgenic mouse model of AD that co-expresses mouse/human chimaeric APP (amyloid precursor protein with the Swedish mutation and human presenilin-1 with a deletion of exon 9. Although accumulation of Aβ was confirmed in the double-Tg mouse brains and sera, no statistically significant change was detected in the concentration and composition of major ganglio-N-tetraosyl-series gangliosides in the double-Tg brain. Most interestingly, Chol-1α antigens (cholinergic neuron-specific gangliosides, such as GT1aα and GQ1bα, which are minor species in the brain, were found to be increased in the double-Tg mouse brain. We interpret that the occurrence of these gangliosides may represent evidence for generation of cholinergic neurons in the AD brain, as a result of compensatory neurogenesis activated by the presence of Aβ.

  18. eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Xing Hua Tang

    Full Text Available We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs.Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

  19. Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue

    Directory of Open Access Journals (Sweden)

    Ravid Rivka

    2008-05-01

    Full Text Available Abstract Background Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD, Parkinson's disease (PD and dementia with Lewy bodies (DLB. Quantitative real-time PCR (RT qPCR is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB. Results The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], β-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA] in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan® Gene Expression Assays. Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis. Conclusion This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.

  20. Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

    Directory of Open Access Journals (Sweden)

    Daniela Santucci

    Full Text Available Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF and brain derived neurotrophic factor (BDNF, were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occurred only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.

  1. Expression of p21-activated kinases 1 and 3 is altered in the brain of subjects with depression.

    Science.gov (United States)

    Fuchsova, Beata; Alvarez Juliá, Anabel; Rizavi, Hooriyah S; Frasch, Alberto Carlos; Pandey, Ghanshyam N

    2016-10-01

    The p21-activated kinases (PAKs) of group I are the main effectors for the small Rho GTPases, critically involved in neurodevelopment, plasticity and maturation of the nervous system. Moreover, the neuronal complexity controlled by PAK1/PAK3 signaling determines the postnatal brain size and synaptic properties. Stress induces alterations at the level of structural and functional synaptic plasticity accompanied by reductions in size and activity of the hippocampus and the prefrontal cortex (PFC). These abnormalities are likely to contribute to the pathology of depression and, in part, reflect impaired cytoskeleton remodeling pointing to the role of Rho GTPase signaling. Thus, the present study assessed the expression of the group I PAKs and their activators in the brain of depressed subjects. Using quantitative polymerase chain reaction (qPCR), mRNA levels and coexpression of the group I PAKs: PAK1, PAK2, and PAK3 as well as of their activators: RAC1, CDC42 and ARHGEF7 were examined in postmortem samples from the PFC (n=25) and the hippocampus (n=23) of subjects with depression and compared to control subjects (PFC n=24; hippocampus n=21). Results demonstrated that mRNA levels of PAK1 and PAK3, are significantly reduced in the brain of depressed subjects, with PAK1 being reduced in the PFC and PAK3 in the hippocampus. No differences were observed for the ubiquitously expressed PAK2. Following analysis of gene coexpression demonstrated disruption of coordinated gene expression in the brain of subjects with depression. Abnormalities in mRNA expression of PAK1 and PAK3 as well as their altered coexpression patterns were detected in the brain of subjects with depression. PMID:27474226

  2. Mouse Social Network Dynamics and Community Structure are Associated with Plasticity-Related Brain Gene Expression.

    Science.gov (United States)

    Williamson, Cait M; Franks, Becca; Curley, James P

    2016-01-01

    Laboratory studies of social behavior have typically focused on dyadic interactions occurring within a limited spatiotemporal context. However, this strategy prevents analyses of the dynamics of group social behavior and constrains identification of the biological pathways mediating individual differences in behavior. In the current study, we aimed to identify the spatiotemporal dynamics and hierarchical organization of a large social network of male mice. We also sought to determine if standard assays of social and exploratory behavior are predictive of social behavior in this social network and whether individual network position was associated with the mRNA expression of two plasticity-related genes, DNA methyltransferase 1 and 3a. Mice were observed to form a hierarchically organized social network and self-organized into two separate social network communities. Members of both communities exhibited distinct patterns of socio-spatial organization within the vivaria that was not limited to only agonistic interactions. We further established that exploratory and social behaviors in standard behavioral assays conducted prior to placing the mice into the large group was predictive of initial network position and behavior but were not associated with final social network position. Finally, we determined that social network position is associated with variation in mRNA levels of two neural plasticity genes, DNMT1 and DNMT3a, in the hippocampus but not the mPOA. This work demonstrates the importance of understanding the role of social context and complex social dynamics in determining the relationship between individual differences in social behavior and brain gene expression. PMID:27540359

  3. Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

    Science.gov (United States)

    El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

    2016-04-01

    In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

  4. Bacterial Colonization and the Expression of Inducible Nitric Oxide Synthase in Murine Wounds

    Science.gov (United States)

    Mahoney, Eric; Reichner, Jonathan; Robinson Bostom, Leslie; Mastrofrancesco, Balduino; Henry, William; Albina, Jorge

    2002-01-01

    The expression of inducible nitric oxide synthase (iNOS) in two different murine wound models was investigated. Animals were subjected to either full-thickness linear skin incision with subcutaneous implantation of sterile polyvinyl alcohol sponges, or to 1.5 × 1.5-cm dorsal skin excision. Reverse transcriptase-polymerase chain reaction detected iNOS mRNA in all cell samples retrieved from the sponges. Immunoblotting of lysates of inflammatory cells harvested from the sponges failed to detect iNOS protein, and immunohistochemistry of the incisional wound was mildly positive. Inflammatory cells of excisional wounds stained strongly positive for iNOS. Cutaneous wounds were found to be colonized with Staphylococcus aureus. The detection of iNOS in cells from sponges inoculated in vivo with heat-killed bacteria and the reduction of immunohistochemical signal for iNOS in excisional wounds of animals treated with antibiotics support a role of bacteria in the induction of iNOS in wounds. The expression of iNOS in excisional wounds requires interferon-γ and functional lymphocytes because interferon-γ knockout and SCID-Beige mice exhibited attenuated iNOS staining in excisional wounds. The expression of iNOS in the inflammatory cells of murine wounds is a response to bacterial colonization and not part of the normal repair process elicited by sterile tissue injury. PMID:12466130

  5. SERT and nNOS expression in the choroid plexus of buffalo brain

    Directory of Open Access Journals (Sweden)

    G. Scala

    2010-02-01

    Full Text Available Serotonin (5-HT is a well recognized neurotransmitter in the mammalian central nervous system (CNS. It regulates a variety of physiological functions such as sleep, pain, thermoregulation, feeding, sexual behaviour, and mood. An important component of the 5-HT system is the serotonin transporter SERT which regulates 5-HT homeostasis. Nitric oxide (NO acts as an intercellular messenger in the CNS, and exerts profound effects on the neuroendocrine functions and behaviour. Within neurons, NO is produced by the activity of one of the isoform of NO synthases present in the organism, namely neuronal NO synthase (nNOS. Although a different anatomical distribution of the central neurons synthetizing 5-HT and NO-producing neurons, functional interactions have been demonstrated between the central 5-HT- and NO-generating systems. Recent data indicate that NO may regulate both the intracellular amount of the amine and its intracellular availability by controlling the release and uptake of 5-HT. In this study, we demonstrated the expression of both SERT and nNOS in the choroid plexuses of buffalo brain by scanning electron microscopy (SEM and biochemical analyses. Our findings may provide some insights into the mechanism by which the choroid plexus specific barrier acts for the regulation of the most basic neural functions.

  6. PDM-ENLOR for segmentation of mouse brain gene expression images.

    Science.gov (United States)

    Le, Yen H; Kurkure, Uday; Kakadiaris, Ioannis A

    2015-02-01

    Statistical shape models, such as Active Shape Models (ASMs), suffer from their inability to represent a large range of variations of a complex shape and to account for the large errors in detection of (point) landmarks. We propose a method, PDM-ENLOR (Point Distribution Model-based ENsemble of LOcal Regressors), that overcomes these limitations by locating each landmark individually using an ensemble of local regression models and appearance cues from selected landmarks. We first detect a set of reference landmarks which were selected based on their saliency during training. For each landmark, an ensemble of regressors is built. From the locations of the detected reference landmarks, each regressor infers a candidate location for that landmark using local geometric constraints, encoded by a point distribution model (PDM). The final location of that point is determined as a weighted linear combination, whose coefficients are learned from the training data, of candidates proposed by its ensemble's component regressors. We use multiple subsets of reference landmarks as explanatory variables for the component regressors to provide varying degrees of locality for the models in each ensemble. This helps our ensemble model to capture a larger range of shape variations as compared to a single PDM. We demonstrate the advantages of our method on the challenging problem of segmenting gene expression images of mouse brain. The overall mean and standard deviation of the Dice coefficient overlap over all 14 anatomical regions and all 100 test images were (88.1 ± 9.5)%. PMID:25476414

  7. Common genetic variants and gene expression associated with white matter microstructure in the human brain.

    Science.gov (United States)

    Sprooten, Emma; Knowles, Emma E; McKay, D Reese; Göring, Harald H; Curran, Joanne E; Kent, Jack W; Carless, Melanie A; Dyer, Thomas D; Drigalenko, Eugene I; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Kochunov, Peter; Blangero, John; Glahn, David C

    2014-08-15

    Identifying genes that contribute to white matter microstructure should provide insights into the neurobiological processes that regulate white matter development, plasticity and pathology. We detected five significant SNPs using genome-wide association analysis on a global measure of fractional anisotropy in 776 individuals from large extended pedigrees. Genetic correlations and genome-wide association results indicated that the genetic signal was largely homogeneous across white matter regions. Using RNA transcripts derived from lymphocytes in the same individuals, we identified two genes (GNA13 and CCDC91) that are likely to be cis-regulated by top SNPs, and whose expression levels were also genetically correlated with fractional anisotropy. A transcript of HTR7 was phenotypically associated with FA, and was associated with an intronic genome-wide significant SNP. These results encourage further research in the mechanisms by which GNA13, HTR7 and CCDC91 influence brain structure, and emphasize a role for g-protein signaling in the development and maintenance of white matter microstructure in health and disease. PMID:24736177

  8. Brain Basics

    Medline Plus

    Full Text Available ... of brain scan called magnetoencephalography, or MEG, can capture split-second changes in the brain. Using MEG, ... The study of how environmental factors like diet, stress and post-natal care can change gene expression ( ...

  9. Identification of Vulnerable Cell Types in Major Brain Disorders Using Single Cell Transcriptomes and Expression Weighted Cell Type Enrichment.

    Science.gov (United States)

    Skene, Nathan G; Grant, Seth G N

    2016-01-01

    The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE) method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer's disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer's and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesized that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer's disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models. PMID:26858593

  10. Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease.

    Science.gov (United States)

    Minjarez, Benito; Calderón-González, Karla Grisel; Valero Rustarazo, Ma Luz; Herrera-Aguirre, María Esther; Labra-Barrios, María Luisa; Rincon-Limas, Diego E; Sánchez Del Pino, Manuel M; Mena, Raul; Luna-Arias, Juan Pedro

    2016-06-01

    Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article "Identification of proteins that are differentially expressed in brains with Alzheimer's disease using iTRAQ labeling and tandem mass spectrometry" (Minjarez et al., 2016) [1]. PMID:27257613

  11. Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats.

    Science.gov (United States)

    Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna; Hatch, Kayla N; Henricks, Angela; Scott, Samantha; Hood, Lauren E; Neisewander, Janet L

    2016-10-15

    Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline+Isolated, (2) Nicotine+Isolated, (3) Saline+Social, or (4) Nicotine+Social. For Experiment 1, brain tissue was collected 90min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects. PMID:27435419

  12. Modulation of gamma-irradiation and carbon tetrachloride induced oxidative stress in the brain of female rats by flaxseed oil.

    Science.gov (United States)

    Ismail, Amel F M; Salem, Asmaa A M; Eassawy, Mamdouh M T

    2016-08-01

    The activity of flaxseed oil (FSO) on gamma-irradiation (7Gy) and/or carbon tetrachloride (CCl4) induced acute neurotoxicity in rats' brain was investigated. The results revealed a significant decrease (poxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), transforming growth factor-beta-1 (TGF-β1), iron (Fe), calcium (Ca), copper (Cu) and magnesium (Mg) levels were observed. Furthermore, the relative ratio of xanthine oxidase (XO) and inducible nitric-oxide synthase (iNOS) gene expression levels were elevated in the brain tissues of γ-irradiated and CCl4 intoxicated animals. Those effects were augmented due to the effect of CCl4-induced toxicity in γ-irradiated rats. The treatment of FSO displayed significant amendment of the studied parameters in the brain tissues of γ-irradiated and CCl4 intoxicated animals. FSO has a neuroprotective effect against CCl4-induced brain injury in gamma-irradiated rats. This effect is interrelated to the ability of FSO to scavenges the free radicals, enhances the antioxidant enzymes activity, increases GSH contents, down-regulates the inflammatory responses, ameliorates the iron, calcium, copper, magnesium, manganese levels and inhibiting the gene expression level of XO and iNOS in the brain tissues of intoxicated animals. In conclusion, this study demonstrated that the potent antioxidant and anti-inflammatory activities of FSO have the ability to improve the antioxidant status, suppress the inflammatory responses, and regulate the trace elements in the brain tissues of γ-irradiated, CCl4, and their combined effect in intoxicated animals. Consequently, FSO exhibited neuroprotective activity on γ-irradiated, CCl4, and their combined effect induced brain injury in rats. PMID:27232147

  13. India-based neutrino observatory (INO): Physics reach and status report

    International Nuclear Information System (INIS)

    We present a review of the physics reach and current status of the proposed India-based Neutrino Observatory (INO). We briefly outline details of the INO location and the present status of detector development. We then present the physics goals and simulation studies of the main detector, the magnetised Iron Calorimeter (ICAL) detector, to be housed in INO. The ICAL detector would make precision measurements of neutrino oscillation parameters with atmospheric neutrinos including a measurement of the neutrino mass hierarchy. Additional synergies with other experiments due to the complete insensitivity of ICAL to the CP phase are also discussed

  14. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Erickson Michelle A

    2011-10-01

    Full Text Available Abstract Background Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. However, very little is known about their immune activities or their roles in neuroinflammation. Here, we focused on the immunological profile of brain pericytes in culture in the quiescent and immune-challenged state by studying their production of immune mediators such as nitric oxide (NO, cytokines, and chemokines. We also examined the effects of immune challenge on pericyte expression of low density lipoprotein receptor-related protein-1 (LRP-1, a protein involved in the processing of amyloid precursor protein and the brain-to-blood efflux of amyloid-β peptide. Methods Supernatants were collected from primary cultures of mouse brain pericytes. Release of nitric oxide (NO was measured by the Griess reaction and the level of S-nitrosylation of pericyte proteins measured with a modified "biotin-switch" method. Specific mitogen-activated protein kinase (MAPK pathway inhibitors were used to determine involvement of these pathways on NO production. Cytokines and chemokines were analyzed by multianalyte technology. The expression of both subunits of LRP-1 was analyzed by western blot. Results Lipopolysaccharide (LPS induced release of NO by pericytes in a dose-dependent manner that was mediated through MAPK pathways. Nitrative stress resulted in S-nitrosylation of cellular proteins. Eighteen of twenty-three cytokines measured were released constitutively by pericytes or with stimulation by LPS, including interleukin (IL-12, IL-13, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, eotaxin, chemokine (C-C motif ligand (CCL-3, and CCL-4. Pericyte expressions of both subunits of

  15. Systemic administration of 6-OHDA to rhesus monkeys upregulates HLA-DR expression in brain microvasculature

    Directory of Open Access Journals (Sweden)

    Joers V

    2014-09-01

    Full Text Available Valerie Joers,1,2 Scott Vermilyea,1,2 Kristine Dilley,1 Marina E Emborg1–3 1Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, 2Neuroscience Training Program, 3Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA Background: We recently developed a nonhuman primate model of cardiac dysautonomia by systemic dosing of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA. The aim of this study was to assess whether systemic 6-OHDA affects the central nervous system of nonhuman primates, in particular the dopaminergic nigrostriatal system. Methods: Brain sections from adult rhesus monkeys that received systemic 6-OHDA (50 mg/kg intravenously; n=5 and were necropsied 3 months later, as well as normal controls (n=5 were used in this study. Tissue was cut frozen at 40 µm on a sliding microtome, processed for immunohistochemistry, and blindly evaluated. Results: Neither the optical density of tyrosine hydroxylase immunoreactivity (TH-ir; a dopaminergic neuronal marker in the caudate and putamen nucleus nor the TH-ir cell number and volume in the substantia nigra showed significant differences between groups. Yet within groups, statistical analysis revealed significant individual differences in the 6-OHDA-treated group, with two animals showing a lower cell count and volume. Optical density quantification of α-synuclein-ir in the substantia nigra did not show differences between groups. As α-synuclein intracellular distribution was noted to vary between animals, it was further evaluated with a semiquantitative scale. A greater intensity and presence of α-synuclein-positive nigral cell bodies was associated with larger TH-positive nigral cell volumes. Increased human leukocyte antigen (HLA-DR; a microglial marker expression was observed in 6-OHDA-treated animals compared with controls. HLA-DR-ir was primarily localized in endothelial cells and perivascular spaces throughout

  16. Enhanced expression of constitutive and inducible forms of nitric oxide synthase in autoimmune encephalomyelitis.

    Science.gov (United States)

    Kim, S; Moon, C; Wie, M B; Kim, H; Tanuma, N; Matsumoto, Y; Shin, T

    2000-06-01

    To elucidate the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), we analyzed the expression of constitutive neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) in the spinal cords of rats with EAE. We further examined the structural interaction between apoptotic cells and spinal cord cells including neurons and astrocytes, which are potent cell types of nitric oxide (NO) production in the brain. Western blot analysis showed that three forms of NOS significantly increased in the spinal cords of rats at the peak stage of EAE, while small amounts of these enzymes were identified in the spinal cords of rats without EAE. Immunohistochemical study showed that the expression of either nNOS or eNOS increased in the brain cells including neurons and astrocytes during the peak and recovery stages of EAE, while the expression of iNOS was found mainly in the inflammatory macrophages in the perivascular EAE lesions. Double labeling showed that apoptotic cells had intimate contacts with either neurons or astrocytes, which are major cell types to express nNOS and eNOS constitutively. Our results suggest that the three NOS may play an important role in the recovery of EAE. PMID:14612615

  17. Co-expression of VAL- and TMT-opsins uncovers ancient photosensory interneurons and motorneurons in the vertebrate brain.

    Directory of Open Access Journals (Sweden)

    Ruth M Fischer

    Full Text Available The functio