ABSTRACT
Objective:To explore the effect of Tuina of Three Handing-Three Points on the recovery of motor function, the expression of neuregulin (NRG) 1 and human epidermal growth factor receptor (ErbB) 2 in the injured point of sciatic nerve and L4-6 spinal cord, and the morphological change of myelin sheath at the injured point of sciatic nerve of rats. Methods:A total of 76 male Sprague-Dawley rats were randomly divided into normal group, sham operation group, model group and Tuina group with 19 rats in each group. The right side sciatic nerve was clamped to make model in the model group and Tuina group. The sham operation group exposed sciatic nerve only. Tuina group received Tuina on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34) with dialing, plucking and kneading using Tuina technique simulator. All of them were tested with Oblique Plate Test before modeling, seven days and 28 days after modeling. Western blotting was used to detect the protein expression of NRG1 and ErbB2 in the injured point of sciatic nerve and L4-6 spinal cord. The change of myelin sheath at the sciatic nerve injury point was observed and analyzed by transmission electron microscope. Results:Seven days and 28 days after modeling, the scores of Oblique Plate Test were lower in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05); 28 days after modeling, the scores was higher in Tuina group than in the model group (P < 0.05). At the sciatic nerve injury point, three days after modeling, the expression of NRG1 and ErbB2 was higher in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05); seven days and 28 days after modeling, there was no significant difference in NRG1 among groups (P > 0.05); 28 days after modeling, the expression of ErbB2 was higher in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05). In L4-6 spinal cord, three days after modeling, the expression of NRG1 and ErbB2 was higher in the model group and Tuina group than in the normal group and sham operation group (P < 0.05); seven days after modeling, the expression of NRG1 was higher in the model group and Tuina group than in the sham operation group (P < 0.05), and the expression of ErbB2 was higher in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05); 28 days after modeling, the expression of NRG1 was higher in Tuina group than in the model group (P < 0.05), and there was no significant difference in ErbB2 among groups (P > 0.05). The electron microscope showed that, 28 days after modeling, the myelin sheath collapsed seriously in the model group; while the ultrastructure of the nerve injury point improved, and the myelin sheath of the nerve fiber was relatively intact in Tuina group; the g-ratio value was lower in the model group than in the sham operation group (P < 0.05), the g-ratio value was higher in Tuina group than in the model group (P < 0.05), and no difference was found in g-ratio value between Tuina group and sham operation group (P > 0.05). Conclusion:Three Handing-Three Points could improve the motor function of hind limbs in rats with sciatic nerve injury, which may be related to the adjustment of NRG1 and ErbB2 in the sciatic nerve and spinal cord, to maintain normal myelin sheath structure.
ABSTRACT
Objective To investigate the serum levels of neuregulin-1 (NRG-1) and the gamma activity of the prefrontal cortex of electroencephalogram (EEG) in the resting state in first-episode schizophrenia patients and exam﹣ine their correlation with clinical symptoms and cognitive function. Methods The serum levels of NRG-1 were mea﹣sured in 53 patients and 58 controls. The gamma activity was first collected from the lead of FP1 and FP2 of the pre﹣frontal cortex of EEG and was then measured by using time-frequency analysis. The psychotic symptoms were as﹣sessed by positive and negative syndrome scale (PANSS). The MATRICS consensus cognitive battery (MCCB) was used to assess the cognitive function. Results The serum levels of NRG-1 was significantly lower in the case group than in the control [(7.36±3.96) pg/mL vs. (11.02±8.78) pg/mL, P=0.006]. The gamma activity was significantly different be﹣tween the case group and the control group [39(73.6%) vs. 14(26.4%), P<0.001]. The scores of TMT in MCCB was significantly higher while the scores of BACS SC, HVLT-R, NAB, BVMT-R and CF scores were significantly lower in the case group than the control group (P<0.01). There was a negative correlation between the serum NRG-1 level and the gamma activity in the case group (r=-0.542, P<0.001). There was a negative correlation between the serum NRG-1 level with PANSS (r=-0.360, P=0.009), while the gamma activity was positively correlated with PANSS (r=0.278, P=0.046) in the case group. The serum NRG-1 level was significantly positively correlated with the scores of HVLT-R in the case group (r=0.332, P=0.016), and the gamma activity was significantly negatively correlated with the scores of HVLT-R (r=-0.442, P=0.001) and NAB (r=-0.307, P=0.027). Conclusion The serum NRG-1 level and the gamma activity are correlated with the clinical symptoms and cognitive impairment of patients with first-episode schizophrenia to some degree, suggesting that abnormal neurobiochemical and neuroelectrophysiological reactions exist and interact with each other in the early stage of schizophrenia.
ABSTRACT
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.
Subject(s)
Animals , Male , Mice , Coronary Artery Disease , Electroacupuncture , Mice, Inbred C57BL , Myocardial Ischemia , MyocardiumABSTRACT
Objective To explore the protective effect of neuregulin-1 (NRG-1) on heart function and myocardium in rats with sepsis and its mechanism . Methods Healthy male Sprague-Dawly (SD) rats were divided into three groups according to random number table method, with 6 rats in each group. Sepsis model was established by cecal ligation and puncture (CLP group); rats in sham operation group (sham group) underwent the same procedure except ligation. Rats in NRG-1 pre-treatment group (NRG group) were intravenously injected with recombinant human NGR-1 (rhNRG-1) at the dose of 10 μg/kg through tail vein; rats in CLP group and sham group were treated with the same amount of saline. At 24 hours after CLP, hemodynamic method was used to evaluate the cardiac function, and myocardial morphology was observed with hematoxylin and eosin (HE) staining, enzyme linked immunosorbent assay (ELISA) was used to detect the levels of cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in serum and macrophage migration inhibitor factor (MIF) in myocardial tissue. Results ① heart function: compared with the sham group, the mean arterial pressure (MAP), left ventricular systolic pressure (LVSP) and left ventricular pressure maximal rate of rise and fall (±dp/dt max) were significantly decreased in CLP group and NRG group, while the MAP, LVSP and ±dp/dt max in NRG group were significantly higher than those in CLP group [MAP (mmHg, 1 mmHg = 0.133 kPa): 125.78±8.15 vs. 113.05±5.85, LVSP (mmHg): 151.27±6.79 vs. 139.39±8.05, +dp/dt max (kPa/s): 4 389.59±332.38 vs. 3 706.85±451.31, -dp/dt max (kPa/s): 4 291.42±323.72 vs. 3 691.17±515.44, all 1 <0.05]. ②Myocardial injury: compared with the sham group, the levels of serum cTnT in CLP group and NRG group were significantly increased, while the levels of serum cTnT in NRG group were significantly lower than those in CLP group (ng/L: 206.37±67.28 vs. 344.13±80.95, 1 < 0.05), and the HE staining showed that myocardial pathological changes in NRG group were improved compared with the CLP group. ③Inflammatory mediators level: compared with the sham group, the levels of serum TNF-α, IL-1β and myocardial MIF were significantly increased in CLP group and NRG group, while the indicators in NRG group were lower than those in CLP group [TNF-α(ng/L): 52.77±3.43 vs. 97.19±13.98, IL-1β (ng/L): 40.25±5.48 vs. 56.05±6.88, MIF (μg/L): 1.92±0.16 vs. 2.87±0.10, all 1 <0.05]. Conclusion NRG-1 can reduce circulating levels of inflammatory factors in rats with sepsis, adjust myocardial MIF level, and alleviate myocardial cell injury, thereby improving cardiac function, and play a role in myocardial protection.
ABSTRACT
Objective:To investigate the effect of NRG-1 on cardiomyocyte apoptosis and oxidative damage under hypoxia reox-ygenation.Methods:The myocardial cell HCM was taken as the object of study.The hypoxia reoxygenation of myocardial cell model was established,and NRG-1 at dose of 0.8 mg/L was added before hypoxia.The cell viability was measured by MTT assay and apoptosis was analyzed by flow cytometry.The level of lactate dehydrogenase(LDH) in the supernatant was detected by 2,4-dinitrophe-nylhydrazine colorimetry assay,DCFH-DA method was used to detected ROS level,the level of MDA was measured by thiobarbituric acid method,the level of SOD was detected by xanthine oxidase method,and the protein levels of Akt and p-AktThr308were determined by Western blot.Results:The A values of the myocardial cells after hypoxia reoxygenation were changed from 0.66±0.03 to 0.36±0.04, the rate of apoptosis increased from (4.62±0.97)% to (29.07±3.43)%,the level of ROS increased from 69.29±7.96 to 280.84± 20.52,the levels of LDH and MDA also increased,and the levels of SOD and p-AktThr308/Akt decreased.After NRG-1 treatment,the A values of the cells were from 0.36±0.04 to 0.47±0.05,the rate of apoptosis decreased from (29.07±3.43)% to (19.76±3.41)%, the ROS levels decreased from 280.84±20.52 to 128.23±12.32,the levels of LDH and MDA also decreased,and the levels of SOD and p-Akt/Akt increased.Conclusion: NRG-1partly inhibits cardiomyocyte apoptosis and oxidative damage induced by hypoxia reoxygenation by affecting the protein levels of p-Akt/Akt in the cardiomyocytes.
ABSTRACT
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.
ABSTRACT
Abstract Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, the expression of NGF, IL-1β, TNF-α in spinal cord were determined. Results: Compared with the diabetic group, NRG1 treatment improved the mechanical withdrawal threshold in diabetic rats, pathological changes of dorsal root ganglion and sural nerve were alleviated by NRG1 treatment with electron microscopy imagine. Moreover, compared with the control group, the expression of NGF was significantly decreased and the production of IL-1β, TNF-α were markedly induced in diabetic group. Furthermore, NRG1 treatment could normalized the above effect as compared to diabetic group. Conclusion: NRG1 exerted positive effects on the behavioral and pathological changes of rats with STZ-induced diabetic neuropathic pain, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.
Subject(s)
Animals , Male , Rats , Neuregulin-1/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetic Neuropathies/drug therapy , Neuralgia/drug therapy , Spinal Cord/metabolism , Random Allocation , Tumor Necrosis Factor-alpha/metabolism , Rats, Sprague-Dawley , Streptozocin , Nerve Growth Factor/metabolism , Interleukin-1beta/metabolism , Neuralgia/etiologyABSTRACT
Neuregulin-1 (NRG-1) can bind with its tyrosine kinase receptor via paracrine and autocrine, activate downstream pathways and perform a series of biological reactions, and reduce pressure load and improve heart function through inhibiting sympathetic nerve excitement.Recent study identified that NRG-1 can induce pluripotent stem cell differentiation;clinical trials proved that recombinant human NRG-1 can reduce level of N terminal pro brain natriuretic peptide, rehospitalization rate and onset times of heart failure.The present article made a review on research progress of NRG-1 in cardiovascular field.
ABSTRACT
AIM:To study the effect of neuregulin-1 ( NRG-1β) or captopril alone and their combination on myocardial cell apoptosis and related gene expression in rats with chronic heart failure .METHODS:Young male Sprague-Dawley rats were randomly divided into sham-operated group, heart failure group, NRG-1βgroup, captopril group and combined treatment group .The volume overloaded heart failure model in the rats was established by aortocaval fistula .The cardiac function was evaluated by determining the changes of hemodynamics and plasma BNP level .The apoptotic index ( AI) of myocardial cells was assayed by TUNEL .The protein levels of p-Akt, Bax and Bcl-2 in left ventricular tissue were detected by Western blot .RESULTS: The LVEDP, AI and the expression of Bax were significantly lower in NRG-1βgroup, captopril group and combined treatment group than those in heart failure group ( P<0.05 ) , while the values of ±dp/dtmax and the protein levels of p-Akt and Bcl-2 were significantly higher in NRG-1βgroup, captopril group and com-bined treatment group than those in heart failure group (P<0.05).The effect of combined treatment group was more signifi-cant ( P<0.05) than that in NRG-1βgroup and captopril group .CONCLUSION: Neuregulin-1βor captopril alone and the combination of them effectively improve the cardiac function and inhibit myocardial cell apoptosis in chronic heart failure rats.The therapeutic effect of combination of NRG-1βand captopril is better than that of NRG-1βor captopril alone .
ABSTRACT
Neuregulin-1 (NRG-1) and the ErbBs family of receptor tyrosine kinases are widely expressed in the cardiovascular system.NRG-1/ErbBs signaling plays an essential role in physiology and pathophysiology of the heart,including stabilization of cardiac myocyte structure and function,promotion of cardiac myocyte proliferation and survival,inhibition of cardiac myocyte apoptosis,reduction of myocardial interstitial fibrosis,regulation of energy utilization,and enhancement of angiogenesis and so on.Therefore,NRG-1/ErbBs signaling is involved in the development and treatment of chronic heart failure(CHF).In this review,we bring the growing literature on NRG-1/ErbBs signaling and its significance in cardiovascular development and heart failure.
ABSTRACT
The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.
Subject(s)
Animals , Mice , Mice, Knockout , Motor Endplate , Muscle, Skeletal , Muscles , Myelin Sheath , Neuregulin-1 , Neuromuscular Junction , Peripheral Nerves , Presynaptic Terminals , Protein-Tyrosine Kinases , Schwann Cells , Synapses , VertebratesABSTRACT
Objective: To study the protective roll of neuregulin-1 (NRG-1) on high glucose caused myocardial cell injury in rat’s embryo H9c2 myocardial cells with its mechanism. Methods: Cultured rat’s embryo H9c2 myocardial cells were divided into 5 groups:①Control group,②High glucose (HG) group, containing glucose 33 mmol/L,③HG+NRG-1 10 nmol/L (N1) group,④HG+NRG-1 50 nmol/L (N2) group and⑤HG+NRG-1 250 nmol/L (N3) group. All cells were treated for 24 hours. Myocardial cell survival rate was measured by CCK-8 method, intracellular reactive oxygen species (ROS) level and the apoptosis rate were detected by lfow cytometry, enzymes activities of CK, LDH, SOD and MDA content were examined, proteins expressions of NRG-1 receptor as ErbB2 and ErbB4 were assessed by Western blot analysis. NRG-1 treated myocardial cell apoptosis in type II diabetic cardiomyopathy rats was observed by Tunel staining. Results: Compared with HG group, from N1 group to N3 group, myocardial cell survival rates were increased from (63.33±3.56) %to (85.88±4.55) %, ROS levels decrease form (33.75±4.23) % to (15.88±4.55) %, apoptosis rates reduced from (36.44±4.86) % to (14.77±4.21) %, receptor expressions of ErbB2 was elevated from (0.26±0.04) to (0.84±0.03) and ErbB4 was elevated from (0.39±0.03) to (0.72±0.04), allP<0.05; enzymes activities of CK, LDH and MDA content were gradually decreased and SOD activity was gradually increased, allP<0.05. NRG-1 treated myocardial cell apoptosis in type II diabetic cardiomyopathy rats was also obviously reduced. Conclusion: NRG-1 could increase the survival rate and reduce the oxidative stress injury and apoptosis of cultured rat’s embryo H9c2 myocardial cells in HG condition which might be related to NRG-1 binding to ErbB2/ErbB4 molecules in the cells.
ABSTRACT
Objective To investigate the influence of recombinant neuregulin-1 beta (rhNRG-1β) on neural stem cell proliferation through extracellular regulated protein kinases (ERK) signaling pathway in oxygen and glucose deprivation (OGD) environment.Methods Neural stem cells were obtained from embryonic brain of mice pregnant for 14-17 d,cultured and identified by immunochemical staining through detection of the indicator nestin using the SABC-FITC (POD)double standard kit.Neural stem cells were divided into three experiment groups (OGD group,control group and OGD + rhNRG-1β group).Control group:identified neural stem cells,2 × 107,were cultured for 3 h in the 24-hole culture plate with DMEM/F12 complete culture medium;OGD group:neural stem cells,2 × 107,were cultured in the 24-hole culture plate deprived glucose DMEM/F12 in a wet airtight container (37 ℃ constant temperature),cells were cultured with mixed gas of nitrogen (950 ml/L) and oxygen (50 ml/L) for 1 h,and then the culture medium was replaced with complete culture medium and cultured for 3 h;OGD + rhNRG-1β group:before OGD intervention,100 μg/L rhNRG-1β was given for 3 h.Neurospheres formation:the three groups of stem cells were dispersed into single cells,1 × 106/ml cells were inoculated to culture plates containing cover slips coated with poly lysine,and cultivated for 7 d,and neurospheres formation of the 3 groups of neural stem cells was observed under microscope,which was aimed to record neural stem cells proliferation changes.Colony formation:the three groups of stem cells,vaccinated in 60 mm in a petri dish,2 × 107 in number,were cultivated in complete culture medium for 24 h.The colony formation of the three groups of cells was observed under microscope,and neural stem cells proliferation changes were observed.Western blotting:the change of phosphorylation ERK (pERK) protein of the three groups of stem cells was determined,and the effect of pERK protein expression regulated by rhNRG-1β in mice neural stem cells proliferation through ERK signaling pathway was observed.Results Microscopically the primary cultured stem cells grew in single or in pairs,in a round shape;neural stem cell proliferated in clumps or colony;neural stem cells expressed the specificity of nestin protein markers with fluorescent yellow-green color.The differences in the aspects of the average diameter of neurospheres and neurospheres quantity in the neural stem cells between groups were statistically significant (F =693.66,1 002.09,all P ＜ 0.01),and among them the neuropheres formation of OGD group was significantly suppressed.Formation quantity and average diameter in OGD group [(88.78 ± 7.14) numbers,(62.12 ± 2.52) μm] were significantly lower than those in the control group [(246.34 ± 8.67) numbers,(128.45 ± 2.33) μm] and those in OGD + rhNRG-1β group [(237.87 ± 6.61) numbers,(118.37 ± 2.71) μm,all P ＜ 0.01].The difference of colony formation rate of neural stem cell was statistically significant (F =132.03,P ＜ 0.01),and among them colony formation of OGD group significantly suppressed.Formation rate in OGD group [(11.65 ± 0.94)％] was significantly lower than that in the control group [(33.23 ± 2.93)％] and that in OGD + rhNRG-1β group [(31.42 ± 2.61)％,all P ＜ 0.01].Western blotting showed that the difference of pERK protein expression of neural stem cells between groups was statistically significant (F =63.76,P ＜ 0.01).Relative expression of the pERK protein in OGD group (0.487 ± 0.072) was significantly lower than that in the control group (1.013 ± 0.112) and that in OGD + rh-NRG-1β group (1.752 ± 0.278,all P ＜ 0.01).Conclusion rhNRG-1β preserves neural stem cell proliferation with phosphorylation ERK protein expression up-regulated in oxygen and glucose deprivation environment.
ABSTRACT
Objective To study the association of neuregulin 1(NRG1)gene SNPrs2954041 polymorphisms with schizophrenia and cognitive function.Methods 70 psychiatric patients were selected as observation group, 70 healthy persons were selected as control group.NRG1 gene SNPrs2954041 polymorphism was detected,and the patients'cognitive function and neurological NSS score were evaluated.Results The differences of SNPrs2954041 polymorphism genotype and allele frequencies between the two groups were statistically significant(χ2 =35.412,29.341, all P =0.000).The differences in genotype and allele frequencies between the male observation patients and male control group were statistically significant(χ2 =24.571 ,18.391 ,all P =0.000).The differences in genotype and allelefrequencies between female the observation patients and female control group were statistically significant (χ2 =14.145,13.024,all P =0.000).The difference of memory understanding among the three groups was statistically sig-nificant(F =3.781,P =0.031).The difference of digit span,correct number,errors number,errors continued num-ber,non -sustained errors number in three groups showed no significant differences(F =0.702,0.125,0.089, 0.692,0.113,P =0.498,0.882,0.927,0.512,0.748),the difference of neurological soft signs score of T/T geno-type[(6.79 ±0.55)points],T/G genotype[(6.88 ±0.51 )points]and G/G genotype[(6.53 ±0.39)points]in schizophrenia group was not statistically significant(F =0.142,P =0.843).Conclusion NRG1 gene SNPrs2954041 polymorphism was related to schizophrenia and cognitive function in patients with schizophrenia.
ABSTRACT
Objective To observe the effects of neuregulin‐1 (NRG‐1)on calcium transients in mouse ventricular myo‐cytes.Methods Nine C57BL/6 mice of male were randomly dived into 3 groups :the blank control group ,NRG‐1 group ,and iso‐proterenol(ISO)group.Their hearts were removed and immediately cannulated via the aorta and retrogradely perfused with en‐zymatic isolation solution to get single ventricular cell by Langendorff system.Myocytes were loaded with the Ca2+ indicator Fluo‐4 and subjected to electrical field stimulation at 0.5 or 1 Hz by using living cells workstation.The change of fluorescene in‐tensity was recorded simultaneously in each group.Results Compared with the blank control group ,NRG‐1 group had signifi‐cantly increased Ca2+ transient amplitude ΔF/F0 (n=10 ,P0.05).Conclusion NRG‐1 can increase Ca2+ transient amplitude and Ca2+ transients and reduce the time interval of Ca2+ transients.
ABSTRACT
PURPOSE: The aim of this study was to evaluate changes in expressions of neuregulin (NRG)1 and erbB2 tyrosine kinase (ErbB2) in bladders of rats with cyclophosphamide (CYP)-induced interstitial cystitis (IC). METHODS: Twenty-four Sprague-Dawley rats were divided into the IC group (n=16) and the control group (n=8). After inducing IC with intraperitoneal CYP injection, expressions of NRG1 and ErbB2 were analyzed using western blotting and reverse transcriptase-polymerase chain reaction. RESULTS: In Western blotting, relative intensities and distributions of both NRG1 and ErbB2 were approximately 1.5- and 3.2-fold higher, respectively, in the IC group than in the control group (mean+/-standard deviation: 1.42+/-0.09 vs. 0.93+/-0.15 and 0.93+/-0.16 vs. 0.29+/-0.08, P<0.05). In the rat bladder samples, mRNA expression levels of NRG1 and ErbB2 were higher in the IC group than in the control group (P<0.05). CONCLUSIONS: Our study has demonstrated significant changes in mRNA expression and immunoreactivity of NRG1 and ErbB2 receptors in the urinary bladder after CYP-induced IC. These results suggest that the up-regulated NRG1 may play a role in inducing an overactive bladder and promoting regeneration in the inflammatory bladder with CYP-induced IC.
Subject(s)
Animals , Rats , Blotting, Western , Cyclophosphamide , Cystitis, Interstitial , Neuregulin-1 , Protein-Tyrosine Kinases , Rats, Sprague-Dawley , Receptor, ErbB-2 , Regeneration , RNA, Messenger , Tyrosine , Urinary Bladder , Urinary Bladder, OveractiveABSTRACT
Objective:To explore the influence of neuregulin- 1 (NRG-1)intervention on pacing threshold of low voltage area in rats after myocardial infarction.Methods:Myocardial infarction model of rat was established via an-terior descending coronary artery ligation.The 34 rats with myocardial infarction were randomly and averagely di-vided into two groups:NRG-1 group (received NRG-1peritoneal injection)and control group (received peritoneal injection of normal saline of the same volume).After two weeks,pacing thresholds were tested in low voltage area related with infarct in rats after myocardial infarction,and Cx43 (an integral membrane protein of the connexin family)expression was measured in low voltage area.Results:After drug intervention two weeks,compared with control group,there was significant reduction in pacing threshold [(1.466±0.503)V vs.(0.7167±0.194)V,P =0.002]in NRG-1 group;there was significant rise in Cx43 expression [(0.30±0.15)vs.(0.95±0.20),P <0.001] in low voltage area in NRG-1 group.Conclusion:Neuregulin-1 significantly reduces pacing threshold of low voltage area in rats after myocardial infarction,the mechanism may be related to increase Cx43 expression and improve e-lectrical conductivity of myocardial cells.
ABSTRACT
Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.
ABSTRACT
Neuregulin 1 (NRG1) is associated with the pathogenesis of schizophrenia through controlling activation and signaling of neurotransmitter receptors. Influence to schizophrenia development by the NRG1 gene may differ in individuals, and genetic polymorphism is one of the factors affecting their differences. Association between three single nucleotide polymorphisms (SNPs) (rs7014762, -1174 A/T; rs11998176, -788 A/T; rs3924999, Arg253Gln) of NRG1 and the development of schizophrenia was analyzed in 221 schizophrneia and 359 control subjects. Polymerase chain reaction and direct sequencing were performed to obtain genotype data of NRG1 SNPs of the subjects. In analysis of genetic data, multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive model) were applied. SNPStats and SPSS 18.0 were used to calculate odds ratio (OR), 95% confidence interval (CI), and p-value of each model. The genotype distributions of rs3924999 were associated with schizophrenia development (OR=0.67, 95% CI=0.47-0.95, p=0.022 in the dominant model and OR=0.69, 95% CI=0.51-0.93, p=0.013 in the log-addtive model) and allelic distributions also showed significant association (OR=0.70, 95% CI=0.52-0.93, p=0.014). The results suggest that rs3924999 of the NRG1 gene may be associated with schizophrenia susceptibility.
Subject(s)
Genotype , Logistic Models , Neuregulin-1 , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Receptors, Neurotransmitter , SchizophreniaABSTRACT
ObjectiveTo analyze the gene expression of neuregulin1 (Nrg1)mRNA and protein in encephalic region and peripheral blood,and to explore the consistency of the expression in central and peripheral in schizophrenia model rat induced by dizocilpine maleate ( MK801 ).Methods30 adult male SD rats were randomly divided into 3 groups ( 10 cases per group):model group injected with MK801 (0.6 mg/kg and 100μl/20 g)on the right rear of ventrolateral compartment,control group 1 ( no treatment) and control group 2 injected with equal volume normal saline.Nrg1 mRNA was measured in peripheral blood and in prefrontal lobe by using semiquantitative RT-PCR in 3 groups,and Nrg1 protein was measured in encephalic region (prefrontal lobe,dentate band and hippocamp) by using immunohistochemistry.ResultsThere was significant difference of the amount of Nrg1 mRNA among 3 groups (for center:F=9.141,P =0.001 ;for peripheral blood F =8.389,P =0.001 ),and it was higher in model group ( center:2.08 ± 0.64; peripheral blood:1.43 ± 0.46) than that in two control groups ( control group1,center:1.17 ± 0.42,peripheral blood:0.78 ± 0.39 ; control group 2,center:1.31 ± 0.44,peripheral blood:0.79 ± 0.37 ),but no statistical significant difference existed between two control groups.There was positive correlation of Nrg1 mRNA between center and periphery.There was significant difference of Nrg1 protein in prefrontal lobe,dentate band and hippocamp among 3 groups ( F value was 7.275,21.50 and 4.619,and P value was 0.003,0.000 and 0.019,respectively),and it was higher in model( 7.71 ± 2.55,11.67 ± 1.83and 10.18 ±2.08,respectively)than that in two control groups( control group 1:4.89 ± 1.06,7.53 ± 1.14 and 7.10 ± 2.52,respectively; control group 2:5.31 ± 1.39,8.10 ± 1.60 and 7.81 ± 2.50),but no statistical significant difference existed between two control groups.ConclusionMK801 can effect on the expression of Nrg1 gene,Nrg1 mRNA and protein increase in MK801 model rat,and the change is synchronous between center and periphery.