Effects of electroacupuncture on sympathetic nerve-related substance in myocardial tissue in mice with myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on sympathetic nerve-related substance in myocardial tissue in mice with myocardial ischemia (MI), and to explore its possible mechanism.@*METHODS@#Thirty adult male C57BL/6 mice were randomly divided into a sham operation group, a model group and an EA group, 10 mice in each one. The model of MI was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the sham operation group were not treated with ligating at left anterior descending branch of coronary artery, but the remaining procedure was similar with the model group. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 Hz/100 Hz of frequency and 2 mA of intensity, 20 min per treatment, once a day for totally 5 days. No EA was given for model group and sham operation group. The electrocardiogram was recorded and △ST value was calculated to evaluate the model. TTC staining was applied to evaluate the infarct size. Immunohistochemical (IHC) method was applied to evaluate the positive nerve fiber density in myocardial tissue. Western blot method was applied to test the protein expression levels of neuregulin-1 (NRG-1), tyrosine hydroxylase (TH), growth associated protein-43 (GAP-43).@*RESULTS@#The electrocardiogram (lead II) results indicated compared with the sham operation group, the S-T segments in the model group and EA group were increased obviously (both <0.01), indicating the MI model was established successfully. The TTC staining results indicated compared with sham operation group, the infarction size was significantly increased in the model group (<0.01); compared with the model group, the infarction size in the EA group was significantly reduced (<0.01). The IHC results indicated compared with the sham operation group, the positive nerve fiber density in myocardial was increased in the model group (<0.01); compared with the model group, the positive nerve fiber density in myocardial was reduced in the EA group (<0.05). The Western blot results indicated compared with the sham operation group, the expression levels of TH, NRG-1 and GAP-43 were significantly increased in the model group (<0.01); compared with the model group, the expression level of TH and GAP-43 were significantly reduced (<0.01) and that of NRG-1 was increased in the EA group (<0.05).@*CONCLUSION@#EA could increase the expression of NRG-1 and reduce the expression of TH and GAP-43 in myocardial tissues in MI mice, which could suppress sympathetic nerve hyperexcitability after infarction to achieve myocardial protection effect.

α-humulene improves schizophrenia via NRG1/ErbB4 signaling pathway / 中草药

Objective: To study the treating mechanism of α-humulene on the schizophrenic mice. Methods: The schizophrenic models were established by dizocilpine maleate (MK801), then different concentrations of α-humulene were used to treat the mice by intragastric administration. Open-field experiment and PPI test were carried out to evaluate the spontaneous activity and sensorimotor gating function of mice. Moreover, the frontal cortex MDA, NO levels and hippocampal NRG1, ErbB4 protein expression was detected. Results: The spontaneous activity, sensorimotor gating function, MDA, NO, NRG1 and ErbB4 levels were significantly changed in model mice when compared with normal mice (P < 0.01). Compared with model group, different concentrations of α-humulene notably inhibited spontaneous activity, improved PPI value, increased NO and MDA content, down-regulated ErbB4 and NRG1 protein expression (P < 0.05, P < 0.01). Conclusion: The schizophrenia abnormal behavior of mice was improved by α-humulene via down-regulating NRG1/ErbB4 signaling pathway, so as to achieve the purpose of treating schizophrenia.

Neuregulin 1/ErbB4 signaling attenuates neuronal cell damage under oxygen-glucose deprivation in primary hippocampal neurons / 대한해부학회지

Electroacupuncture at Quchi and Zusanli points reduces cell apoptosis by activating Nrg-1 and ErbB4 signaling pathways in cerebral ischemia-reperfusion rats / 医学研究生学报

Objective The mechanism of electroacupuncture (EA) in the treatment of neurological dysfunction caused by ischemic stroke remains to be further explored. This study aimed to investigate the effects of EA at the Quchi (LI11) and Zusanli (ST36) points on the expressions of Nrg-1 and ErbB4 proteins and their correlation with the expressions of cell apoptosis-related proteins bcl-2 and Bax in cerebral ischemia-reperfusion (I-R) rats.Methods Totally 160 male adult SD rats were randomly assigned to four groups of equal number: sham operation, middle cerebral artery occlusion-reperfusion (MCAO-R) model, acupoint, and non-acupoint. After MCAO/R modeling, EA was applied at Quchi and Zusanli in the acupoint group and at ipsilateral non-acupoints below the axillary striation and apex of the coccyx in the non-acupoint group. At 3 days after treatment, the protein and mRNA expressions of Bcl-2, Bax, Nrg-1 and ErbB4 were determined by TTC, TUNEL, immunohistochemistry, Western blot, and RT-PCR.Results The neurological deficit score was significantly increased after cerebral I/R injury in the MCAO-R model, acupoint and non-acupoint groups compared with that in the sham operation group (P<0.01). EA therapy markedly reduced the neurological deficit scores (P<0.05), cerebral infarct area (P<0.05) and the number of apoptotic cells (P<0.05), up-regulated the protein expressions of Nrg-1, ErbB4 and Bcl-2 (P<0.05), and down-regulated that of Bax (P<0.05). There was a pronounced increase in the protein and mRNA expressions of Nrg-1 and ErbB4 in the acupoint group compared with the MCAO-R model and non-acupoint groups after cerebral I-R injury (P<0.01).Conclusion EA at the Quchi and Zusanli points has a neuroprotective effect in ischemic brain injury by up-regulating the expressions of endogenous Nrg-1 and its receptor ErbB4 and down-regulating those of Bcl-2 and Bax. The underlying mechanism is probably associated with the Nrg-1/ErbB4 signaling pathway.

Association between Polymorphisms of rs3924999,rs35753505 in NRG1 Gene and the Efficacy of Risperidone in Patients with Schizophrenia / 昆明医科大学学报

Objective To investigate the association between polymorphisms of rs35753505, rs3924999in neuregulin－1 (NRG1) gene and the efficacy of risperidone after 12 weeks treatment in Han patients with schizophrenia from Yunnan of China.Methods A case－control study was conducted: 114 schizophrenic Han inpatients with 12 weeks single therapy of risperidone were randomly selected from July 2012 to March 2013 and 187 normal Han persons whose age and years of education matched the controls.TaqMan allelic genotyping technology was used to analyze NRG1 genotyping.Treatment effect of risperidone was evaluated by the positive and negative symptoms scale (PANSS), PSP, Raven’s Standard Progressive Matrices, Wechsler Intelligence Scale and Number Cancellation Test.Results (1) There was no statistically difference in genotypes, allele frequencies of rs35753505, rs3924999 polymorphic locibetween schizophrenic inpatients and normal persons. (2) The baseline clinical data of patients with schizophrenia in different NRG1 gene polymorphism was not significant. (3) The value difference of Number Cancellation Test One between pre and post treatment of risperidone was related with different genotypes of two polymorphismsin NRG1 gene, there was statistically difference in two genotypes of rs35753505 loci: G/A group was higher than G/G group (P=0.010) and in three genotypes of rs3924999 loci: A/A group was higher than A/G group (P=0.032) . (4) The value difference of Reven's Standard Progressive Matrices between pre and post treatment of risperidone was related with rs35753505 polymorphic loci: G/A group was higher than G/G group (P=0.004) (5) The result of correlation regression analysis between pre and post treatment of risperidone showed that the value difference of Number Cancellation Test Two was related with the baseline clinical data of course,dose,immediate memory,net score of Number Cancellation Test Two,Number Cancellation Test Three and the genotypes of rs35753505 loci.Conclusion After 12 weeks treatment of risperidone: the improvement degree of patients'attention directivity and concentrated force in different genotypes of rs35753505loci was different:G/A group was higher than G/G group.

Desarrollo temprano de las cavidades cardiacas ventriculares: Importancia de la Neuregulina 1 / Early development of cardiac ventricles: Importance of neuregulin 1

Introducción. Los defectos septales ventriculares graves, asociados con un ventrículo hipoplásico y otro hiperplásico o con la ausencia total del tabique interventricular, suelen ser incompatibles con la vida embrionaria y fetal. Pese a su gravedad, no se conocen sus causas. Por marcaje in vivo en embriones de pollo se confirmó la importancia de las trabéculas en la morfogénesis del tabique interventricular. Por manipulación genética en embriones de ratón y aves se determinó que la ausencia de la Neuregulina 1 (NRG1) o sus receptores, además de provocar escasa diferenciación de los miocitos ventriculares y deficiente formación de las trabéculas, determina la muerte prematura del embrión. Con base en estos antecedentes, el objetivo fue determinar el papel real de NRG1 en la trabeculogénesis temprana y su importancia en la regulación de la proliferación y apoptosis. Métodos. Se estableció un modelo de órgano cultivo de corazón de embrión de pollo previo al inicio de la trabeculogénesis. Se realizaron ensayos de inhibición total de la actividad de NRG1 endógena y posterior adición de la proteína exógena a diferentes concentraciones, determinando la actividad cíclica de los miocitos ventriculares con el antígeno nuclear de proliferación celular y la apoptosis con lisotraker. Resultados. El suero fetal bovino promueve la proliferación, pero impacta negativamente la trabeculogénesis. La adición de NRG1 a concentraciones bajas y períodos cortos de incubación no induce trabeculogénesis. En contraste, a concentraciones medias y períodos de cultivo no mayores a 24 horas, tiene un efecto positivo sobre este proceso. También promueve la proliferación y evita la apoptosis del miocardio ventricular. El incremento en la concentración de NRG1 posiblemente provoca un desbalance molecular que favorece la proliferación desordenada pero no la trabeculogénesis. Conclusiones. El entendimiento del papel de NRG1 en la trabeculogénesis aporta datos para conocer las redes moleculares involucradas también en el desarrollo del tabique interventricular, información indispensable para entender el origen de los defectos septales ventriculares graves.

Background. Serious ventricular septal defects associated with hypoplastic and hyperplasic ventricles or total absence of the interventricular septum (IVS) are usually incompatible with embryonic and fetal life. Despite the importance of these cardiac diseases, their causes are not yet known. Using in vivo labeling in the chick embryo, the importance of ventricular trabeculation was confirmed in IVS morphogenesis. Using knockout mice and retrovirus in birds, it was determined that lack of function of neuregulin 1 (NRG1) or their ErbB receptors not only causes deficient differentiation of ventricular myocytes and poor formation of trabeculae, but also determines premature death of the embryos. Based on this background, the aim of this work was to determine the actual role of NRG1 in early trabeculogenesis and its importance in proliferation and apoptosis regulation. Methods. An embryonic chicken heart organ culture system at the age prior to the beginning of the trabeculogenesis process was established. Endogenous activity of NRG1 was inhibited in the organ cultures that were then stimulated with NRG1 at different concentrations. Myocyte proliferation was determined using the proliferating cell nuclear antigen and apoptosis with LysoTracker (LTR). Results. Fetal bovine serum promotes proliferation but negatively impacts trabeculogenesis. Low concentration of NRG1 and short periods of incubation do not induce trabeculogenesis. In contrast, average NRG1 concentrations and cultivation periods not exceeding 24 h have a positive effect on the onset of this process. This also promotes myocardial proliferation but avoids apoptosis. Higher concentrations of NRG1 possibly cause a molecular imbalance that favors untidy proliferation but not trabeculogenesis. Conclusions. Understanding of the role of NRG1 on ventricular trabeculogenesis provides valuable information for the molecular pathways also involved in IVS development. This information is essential for understanding the origin of serious ventricular septal defects.