Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emo...Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.展开更多
Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In...Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.展开更多
Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol...Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.展开更多
目的探讨HTR3B基因多态性与头颈部恶性肿瘤患者化疗后出现恶心呕吐的关系。方法采用方便抽样的方法,选择行TPF方案化疗的头颈部恶性肿瘤患者212例。从NCBI数据库或既往相关文献中筛选有临床意义的HTR3B基因rs3758987、rs1176744、rs1279...目的探讨HTR3B基因多态性与头颈部恶性肿瘤患者化疗后出现恶心呕吐的关系。方法采用方便抽样的方法,选择行TPF方案化疗的头颈部恶性肿瘤患者212例。从NCBI数据库或既往相关文献中筛选有临床意义的HTR3B基因rs3758987、rs1176744、rs12795805、rs2276305位点,化疗前采集患者外周静脉血3 m L,检测各位点的基因型。分析各位点基因型与化疗后出现恶心呕吐的关系。结果 212例患者化疗后出现恶心呕吐113例,出现恶心呕吐与rs3758987位点有关(P<0.05),与rs1176744、rs12795805、rs2276305位点无关(P均>0.05)。HTR3B基因rs3758987位点TT基因型者化疗后恶心呕吐的发生率明显低于CC+CT基因型者(P<0.05)。结论HTR3B基因rs3758987位点与头颈部恶性肿瘤患者化疗后出现恶心呕吐有关,其CC、CT基因型者化疗后出现恶心呕吐的风险明显高于TT基因型者。展开更多
目的:探讨五羟色胺受体3(5-hydroxytryptamine-3 receptor,5-HTR3)的亚型HTR3E基因非翻译区多态性与中国女性IBS-D的发生及肠道症状的关联.方法:采用聚合酶链反应-限制性片段长度多态性分析(polymerase chain reactionrestriction fragm...目的:探讨五羟色胺受体3(5-hydroxytryptamine-3 receptor,5-HTR3)的亚型HTR3E基因非翻译区多态性与中国女性IBS-D的发生及肠道症状的关联.方法:采用聚合酶链反应-限制性片段长度多态性分析(polymerase chain reactionrestriction fragment length polymorphism,P C R-R F L P)对294例I B S-D女性患者与300例健康对照者HTR3E基因3'端非翻译区c.*76G>A(rs62625044)进行研究.结果:女性患者c.*76G>A多态性位点GA基因型(χ2=6.362,P=0.012)和A等位基因(χ2=5.970,P=0.015)的频率较正常对照均显著升高(P<0.05),GA基因型患者较GG基因型排便频率更高(χ2=7.68,P=0.021),两组患者排便性状也存在很大差异(χ2=6.225,P=0.044).结论:HTR3E的GA基因型和A等位基因可能是中国IBS-D女性患者的易感因素之一;GA基因型的患者较GG基因型肠道症状更加严重.展开更多
基金supported by the National Natural Science Foundation of China(81371213,81070987,and30971531)the grants from the Ministry of Science and Technology of China(2010CB945600 and 2010CB945601)
文摘Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.
基金supported by the Notional Natural Science Foundation of China,Nos.81371213 and 8107098 7the Natural Science Foundation of Shanghai,No.21ZR1468400 (all to QLY)。
文摘Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.
基金supported by the National Key Basic Research and Development Program(NKBRDP)of China(No.2009CB522000)the National Natural Science Foundation of China(No.30971050)+1 种基金the State Key Program of the National Natural Science of China(No.81130020)the Key Program on Basic Science of Henan Science and Technology Department(No.094200510005)
文摘Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.
文摘目的探讨HTR3B基因多态性与头颈部恶性肿瘤患者化疗后出现恶心呕吐的关系。方法采用方便抽样的方法,选择行TPF方案化疗的头颈部恶性肿瘤患者212例。从NCBI数据库或既往相关文献中筛选有临床意义的HTR3B基因rs3758987、rs1176744、rs12795805、rs2276305位点,化疗前采集患者外周静脉血3 m L,检测各位点的基因型。分析各位点基因型与化疗后出现恶心呕吐的关系。结果 212例患者化疗后出现恶心呕吐113例,出现恶心呕吐与rs3758987位点有关(P<0.05),与rs1176744、rs12795805、rs2276305位点无关(P均>0.05)。HTR3B基因rs3758987位点TT基因型者化疗后恶心呕吐的发生率明显低于CC+CT基因型者(P<0.05)。结论HTR3B基因rs3758987位点与头颈部恶性肿瘤患者化疗后出现恶心呕吐有关,其CC、CT基因型者化疗后出现恶心呕吐的风险明显高于TT基因型者。
文摘目的:探讨五羟色胺受体3(5-hydroxytryptamine-3 receptor,5-HTR3)的亚型HTR3E基因非翻译区多态性与中国女性IBS-D的发生及肠道症状的关联.方法:采用聚合酶链反应-限制性片段长度多态性分析(polymerase chain reactionrestriction fragment length polymorphism,P C R-R F L P)对294例I B S-D女性患者与300例健康对照者HTR3E基因3'端非翻译区c.*76G>A(rs62625044)进行研究.结果:女性患者c.*76G>A多态性位点GA基因型(χ2=6.362,P=0.012)和A等位基因(χ2=5.970,P=0.015)的频率较正常对照均显著升高(P<0.05),GA基因型患者较GG基因型排便频率更高(χ2=7.68,P=0.021),两组患者排便性状也存在很大差异(χ2=6.225,P=0.044).结论:HTR3E的GA基因型和A等位基因可能是中国IBS-D女性患者的易感因素之一;GA基因型的患者较GG基因型肠道症状更加严重.
