目的：探讨精神分裂症断裂基因（DISC1）rs821633,rs1000731单核苷酸多态性（SNP）与阿尔茨海默病（AD）的关系.方法提取中国上海汉族441例 AD 患者和749名健康对照组的 DNA,采用 Taqman 探针 SNP 基因分型技术测定 DISC1基因 SNP rs821...目的：探讨精神分裂症断裂基因（DISC1）rs821633,rs1000731单核苷酸多态性（SNP）与阿尔茨海默病（AD）的关系.方法提取中国上海汉族441例 AD 患者和749名健康对照组的 DNA,采用 Taqman 探针 SNP 基因分型技术测定 DISC1基因 SNP rs821633和 rs1000731位点的等位基因及基因型,检测两组受试者等位基因及基因型的频率分布差异.结果两组受试者中 rs821633不符合Hardy－Weinberg 平衡定律给予舍弃,rs1000731符合 Hardy－ Weinberg 平衡定律纳入,rs1000731位点的等位基因及基因型在两组受试者中分布比较,差异无统计学意义（P ＞0．05）.结论 DISC1基因SNP rs1000731与 AD 无明显关联.展开更多
精神分裂症断裂基因1(disrupted in schizophrenia 1,DISC1)是多种精神疾病中的一个关键的遗传学危险因素。DISC1能够与磷酸二酯酶4(phosphodiesterase 4,PDE4)相互作用形成复合物,这可能是一些精神疾病的关键分子机制。PDE4能够水解cAM...精神分裂症断裂基因1(disrupted in schizophrenia 1,DISC1)是多种精神疾病中的一个关键的遗传学危险因素。DISC1能够与磷酸二酯酶4(phosphodiesterase 4,PDE4)相互作用形成复合物,这可能是一些精神疾病的关键分子机制。PDE4能够水解cAMP,DISC1可通过调节PDE4的活性进而发挥调节cAMP在细胞内的信号转导功能。已有研究证实,在一些精神疾病患者中,DISC1和PDE4基因表达均发生了变化。DISC1突变导致其表达产物与PDE4的相互作用减弱,结果之一是降低脑PDE4的活性。DISC1与PDE4之间的相互作用的改变可能是精神分裂症及抑郁症等疾病症状产生的基础。展开更多
A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of th...A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1(DISC1),and animal models in which this gene has some level of dysfunction show emotion-related impairments.However,it is not known whether DISC1 mouse models have an impairment in avoiding potential risks.In the present study,we used DISC1-N terminal truncation(DISC1-N^(TM))mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze(EPM)and showed reduced social preference in a three-chamber social interaction test.Following EPM tests,c-Fos expression levels indicated that the nucleus accumbens(NAc)was associated with risk-avoidance behavior in DISC1-N^(TM)mice.In addition,in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons(FS)in the NAc were significantly lower in DISC1-N^(TM)mice than in wild-type(WT)mice.In addition,in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin(PV)neurons in the NAc of DISC1-N^(TM)mice than in WT controls.The impairment of risk avoidance in DISC1-N^(TM)mice was rescued using optogenetic tools that activated NAcPV neurons.Finally,inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-N^(TM)mice during tests on the elevated zero maze.Taken together,our findings confirm an impairment in risk avoidance in DISC1-N^(TM)mice and suggest that reduced excitability of NAc^(PV) neurons is responsible.展开更多
Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that i...Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.展开更多
Objective: The aim of the present study was to check the potential interaction of two neurodevelopmental proteins, Disc1 and Gas7, in the adult mice brain. Methods: Twenty-four male Swiss albino mice were used for the...Objective: The aim of the present study was to check the potential interaction of two neurodevelopmental proteins, Disc1 and Gas7, in the adult mice brain. Methods: Twenty-four male Swiss albino mice were used for the study. The mice were 12 weeks old in the beginning of the experiment. Immunohistochemistry and co-immunofluorescence were performed on the coronal sections of mice brain and immunoblotting and co-immunoprecipitation were done on the whole brain lysate. Results: Data from immunohistochemistry and co-immunofluorescence indicate the occurrence and co-localization of Disc1 and Gas7 proteins in soma and projections of the brain cells. Immunostaining was observed in cerebral cortex, hypothalamus, midbrain, pons, medulla oblongata and CA3 of hippocampus of the brain. The data from Immunoblotting and co-immunoprecipitation validates the presence and interaction of Disc1 and Gas7 protein in whole brain lysate. Conclusion: Data indicates the potential interaction of Disc1 and Gas7 protein in adult brain. The study highlights the need for further research on Disc1-Gas7 protein interaction in brain development and neuro-disorders.展开更多
Objective To observe the changes of sciatic nerve conduction velocity （SNCV） and interleukin-1α （IL-1α）, phospholipase A2 （PLA2） and prostaglandin E2 （PGE2） in neucleus pulposus tissue in experimental rabbit...Objective To observe the changes of sciatic nerve conduction velocity （SNCV） and interleukin-1α （IL-1α）, phospholipase A2 （PLA2） and prostaglandin E2 （PGE2） in neucleus pulposus tissue in experimental rabbits with lumbar disc herniation （LDH） ; and discuss the mechanism of LDH treated with bloodletting on Wěizhōng （委中 BL40）. Methods 40 normal named control group, LDH model group, BL40 group New Zealand rabbits were randomized into 4 groups, and comparative point group. The experimental LDH model was prepared by the self-made LDH animal pathological modeling device. Bloodletting on BL40 or on comparative point was applied for 7 days. BL-410 physiological signal recorder was used to record SNCV. Enzyme-linked immunosorbent assay （ELISA） and radioimmunology methods were used to determine the contents of IL-1α and PLA2 in neucleus pulposus tissue and PGE2 in serum. Results In BL40 group, SNCV was significantly increased after treatment comparing with that before treatment （P〈0. 01 ）, and the difference in SNCV value before and after treatment was significantly bigger than that in model group and comparative point group （P〈0.05）. Bloodletting on BL40 reduced the contents of IL-1α and PLA2 in neucleus pulposus tissue and serum PGE2 in LDH rabbits, which indicated significant difference or very significant results in the comparison with model and comparative point groups （P〈0.01 or 0. 05）. Conclusion Bloodletting speeded up rapidly SNCV and reduced the contents of inflammatory factors, i.e. IL-1α, PLA2 and serum PGE2 in LDH rabbits, which indicated that alleviation of local inflammatory reaction is probably one of the mechanisms on LDH treated by bloodletting on BL40.展开更多
基金support from the National Key Basic Research and Devdopment Program(973),Grant No.2011CB707805the Natural Science Foundation of China,Grant Nos.81000582 and 60831004+1 种基金the National High Technology Research and Development Program of China(863 Program), Grant No.2009AA02Z302The Beijing Nova Program,Grant No.2010B061
基金supported by the National Natural Science Foundation of China(8117127281301159)+5 种基金the Shanghai Training Plan for Excellent Academic Leaders in Public Health(GWDTR201227)the National Key Clinical Disciplines of the Office of Medical Affairs of the Chinese Ministry of Health at the Shanghai Mental Health Center(OMA-MH2011-873)the Training Plan for Excellent Academic Leaders of the Shanghai Health System(XBR2013087)the Shanghai Mental Health Center Research Grant(2014-YJ-042015-YJGJ-03)
文摘精神分裂症断裂基因1(disrupted in schizophrenia 1,DISC1)是多种精神疾病中的一个关键的遗传学危险因素。DISC1能够与磷酸二酯酶4(phosphodiesterase 4,PDE4)相互作用形成复合物,这可能是一些精神疾病的关键分子机制。PDE4能够水解cAMP,DISC1可通过调节PDE4的活性进而发挥调节cAMP在细胞内的信号转导功能。已有研究证实,在一些精神疾病患者中,DISC1和PDE4基因表达均发生了变化。DISC1突变导致其表达产物与PDE4的相互作用减弱,结果之一是降低脑PDE4的活性。DISC1与PDE4之间的相互作用的改变可能是精神分裂症及抑郁症等疾病症状产生的基础。
基金This work was supported by the National Natural Science Foundation of China(31671116,31761163005,31800881,and 91132306)the International Big Science Program Cultivation Project of Chinese Academy of Sciences(172644KYS820170004)+3 种基金the External Cooperation Program of the Chinese Academy of Sciences(172644KYSB20160057)Science and Technology Program of Guangzhou Municipality(202007030001)the Key-Area Research and Development Program of Guangdong Province(2018B030331001 and 2018B03033600)Shenzhen Government Basic Research Grants(JCYJ20200109115405930 and JCYJ20200109150717745).
文摘A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1(DISC1),and animal models in which this gene has some level of dysfunction show emotion-related impairments.However,it is not known whether DISC1 mouse models have an impairment in avoiding potential risks.In the present study,we used DISC1-N terminal truncation(DISC1-N^(TM))mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze(EPM)and showed reduced social preference in a three-chamber social interaction test.Following EPM tests,c-Fos expression levels indicated that the nucleus accumbens(NAc)was associated with risk-avoidance behavior in DISC1-N^(TM)mice.In addition,in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons(FS)in the NAc were significantly lower in DISC1-N^(TM)mice than in wild-type(WT)mice.In addition,in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin(PV)neurons in the NAc of DISC1-N^(TM)mice than in WT controls.The impairment of risk avoidance in DISC1-N^(TM)mice was rescued using optogenetic tools that activated NAcPV neurons.Finally,inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-N^(TM)mice during tests on the elevated zero maze.Taken together,our findings confirm an impairment in risk avoidance in DISC1-N^(TM)mice and suggest that reduced excitability of NAc^(PV) neurons is responsible.
文摘Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.
文摘Objective: The aim of the present study was to check the potential interaction of two neurodevelopmental proteins, Disc1 and Gas7, in the adult mice brain. Methods: Twenty-four male Swiss albino mice were used for the study. The mice were 12 weeks old in the beginning of the experiment. Immunohistochemistry and co-immunofluorescence were performed on the coronal sections of mice brain and immunoblotting and co-immunoprecipitation were done on the whole brain lysate. Results: Data from immunohistochemistry and co-immunofluorescence indicate the occurrence and co-localization of Disc1 and Gas7 proteins in soma and projections of the brain cells. Immunostaining was observed in cerebral cortex, hypothalamus, midbrain, pons, medulla oblongata and CA3 of hippocampus of the brain. The data from Immunoblotting and co-immunoprecipitation validates the presence and interaction of Disc1 and Gas7 protein in whole brain lysate. Conclusion: Data indicates the potential interaction of Disc1 and Gas7 protein in adult brain. The study highlights the need for further research on Disc1-Gas7 protein interaction in brain development and neuro-disorders.
文摘Objective To observe the changes of sciatic nerve conduction velocity （SNCV） and interleukin-1α （IL-1α）, phospholipase A2 （PLA2） and prostaglandin E2 （PGE2） in neucleus pulposus tissue in experimental rabbits with lumbar disc herniation （LDH） ; and discuss the mechanism of LDH treated with bloodletting on Wěizhōng （委中 BL40）. Methods 40 normal named control group, LDH model group, BL40 group New Zealand rabbits were randomized into 4 groups, and comparative point group. The experimental LDH model was prepared by the self-made LDH animal pathological modeling device. Bloodletting on BL40 or on comparative point was applied for 7 days. BL-410 physiological signal recorder was used to record SNCV. Enzyme-linked immunosorbent assay （ELISA） and radioimmunology methods were used to determine the contents of IL-1α and PLA2 in neucleus pulposus tissue and PGE2 in serum. Results In BL40 group, SNCV was significantly increased after treatment comparing with that before treatment （P〈0. 01 ）, and the difference in SNCV value before and after treatment was significantly bigger than that in model group and comparative point group （P〈0.05）. Bloodletting on BL40 reduced the contents of IL-1α and PLA2 in neucleus pulposus tissue and serum PGE2 in LDH rabbits, which indicated significant difference or very significant results in the comparison with model and comparative point groups （P〈0.01 or 0. 05）. Conclusion Bloodletting speeded up rapidly SNCV and reduced the contents of inflammatory factors, i.e. IL-1α, PLA2 and serum PGE2 in LDH rabbits, which indicated that alleviation of local inflammatory reaction is probably one of the mechanisms on LDH treated by bloodletting on BL40.
