OBJECTIVE Genetic variation in histamine H2 receptor(H2R)and H2R ligands are linked to schizophrenia,however little is known about how H2R contributes to pathogenesis of schizophrenia.Here,we detected a decreased expr...OBJECTIVE Genetic variation in histamine H2 receptor(H2R)and H2R ligands are linked to schizophrenia,however little is known about how H2R contributes to pathogenesis of schizophrenia.Here,we detected a decreased expression of H2R in medial prefrontal cortex(mPFC)glutamatergic neurons in schizophrenia patients.METHODS AND RESULTS Selective knockout of H2R gene(Hrh2)in glutamatergic neurons induced schizophrenia-like behaviors including sensorimotor gating deficit,increased locomotor activity,social withdrawal and anhedo⁃nia in behavior tests,as well as reduced sponta⁃neous firing of mPFC glutamatergic neurons in electrophysiological tests.Selective deletion of the Hrh2 in mPFC glutamatergic neurons but not hippocampus glutamatergic neurons also induced such schizophrenia-like behaviors.Patch-clamp electrophysiology establishes that H2R deficiency reduced the intrinsic excitability of glutamatergic neurons by up-regulation of hyperpolarization activated cyclic nucleotide-gated channels.Fur⁃thermore,either overexpression of H2R in gluta⁃matergic neurons or activation of H2R in the mPFC reversed the MK-801-induced schizophrenia-like symptoms.CONCLUSION H2R can serve as a novel drug target given that functional deficiency of this receptor in mPFC glutamatergic neurons may be crucial for the pathogenesis of schizo⁃phrenia.H2R agonists can be viewed as drug candidates for the treatment of schizophrenia.展开更多
考虑到地磁感应电流(geomagnetically induced current,GIC)具有低频性,过去一直将其近似等效为高压直流输电(high voltage direct current,HVDC)诱发的不平衡电流进行研究。然而,与HVDC型直流偏磁相比,GIC型直流偏磁具有显著的随机性...考虑到地磁感应电流(geomagnetically induced current,GIC)具有低频性,过去一直将其近似等效为高压直流输电(high voltage direct current,HVDC)诱发的不平衡电流进行研究。然而,与HVDC型直流偏磁相比,GIC型直流偏磁具有显著的随机性与时变性,因此简单地将两者完全等效处理并不合理,在特定场景下应加以区分。为此,首先,从理论上分析了两种类型直流偏磁在诱发原因及特点上的差异。其次,通过研究直流偏磁对变压器本体以及电流互感器的不利影响,进一步探究两种类型直流偏磁对电网一/二次设备的影响差异,为后续的偏磁治理提供有效参考。最后,基于PSCAD/EMTDC仿真平台搭建了等效仿真模型,并通过仿真验证了理论分析的正确性。展开更多
基金National Natural Science Foundation of China(81973302)。
文摘OBJECTIVE Genetic variation in histamine H2 receptor(H2R)and H2R ligands are linked to schizophrenia,however little is known about how H2R contributes to pathogenesis of schizophrenia.Here,we detected a decreased expression of H2R in medial prefrontal cortex(mPFC)glutamatergic neurons in schizophrenia patients.METHODS AND RESULTS Selective knockout of H2R gene(Hrh2)in glutamatergic neurons induced schizophrenia-like behaviors including sensorimotor gating deficit,increased locomotor activity,social withdrawal and anhedo⁃nia in behavior tests,as well as reduced sponta⁃neous firing of mPFC glutamatergic neurons in electrophysiological tests.Selective deletion of the Hrh2 in mPFC glutamatergic neurons but not hippocampus glutamatergic neurons also induced such schizophrenia-like behaviors.Patch-clamp electrophysiology establishes that H2R deficiency reduced the intrinsic excitability of glutamatergic neurons by up-regulation of hyperpolarization activated cyclic nucleotide-gated channels.Fur⁃thermore,either overexpression of H2R in gluta⁃matergic neurons or activation of H2R in the mPFC reversed the MK-801-induced schizophrenia-like symptoms.CONCLUSION H2R can serve as a novel drug target given that functional deficiency of this receptor in mPFC glutamatergic neurons may be crucial for the pathogenesis of schizo⁃phrenia.H2R agonists can be viewed as drug candidates for the treatment of schizophrenia.
文摘考虑到地磁感应电流(geomagnetically induced current,GIC)具有低频性,过去一直将其近似等效为高压直流输电(high voltage direct current,HVDC)诱发的不平衡电流进行研究。然而,与HVDC型直流偏磁相比,GIC型直流偏磁具有显著的随机性与时变性,因此简单地将两者完全等效处理并不合理,在特定场景下应加以区分。为此,首先,从理论上分析了两种类型直流偏磁在诱发原因及特点上的差异。其次,通过研究直流偏磁对变压器本体以及电流互感器的不利影响,进一步探究两种类型直流偏磁对电网一/二次设备的影响差异,为后续的偏磁治理提供有效参考。最后,基于PSCAD/EMTDC仿真平台搭建了等效仿真模型,并通过仿真验证了理论分析的正确性。
