Aim Serotonergic neurons in the dorsal raphe nucleus （DRN） are involved in the control of sleep- wake states. Our previous study indicated that calcium （Ca^2＋ ） modulation in the DRN plays an important role in ra...Aim Serotonergic neurons in the dorsal raphe nucleus （DRN） are involved in the control of sleep- wake states. Our previous study indicated that calcium （Ca^2＋ ） modulation in the DRN plays an important role in rapid eye movement sleep （REMS） and non-REMS （NREMS） regulation during pentobarbital hypnosis. Presentstudy was designed to investigate the effects of Ca^2＋ in the DRN on sleep-wake regulation and related neuronal mechanism in freely moving rats. Methods CaC12 （25 or 50 nmol） was microinjected into the DRN and sleep pa- rameters were detective by electroencephalogram （EEG） Monoamine neurotransmitters were detected by HPLC- ECD. c-Fos expression in sleep-wake regulating nucleus was detected by immunohistochemistry. Results Our re- sults showed that microinjection of CaC12 （25 or 50 nmol） into the DRN promoted wakefulness and suppressed NREMS including slow wave sleep （SWS） and REMS in freely moving rats. Meanwhile intro-DRN application of CaC12 （25 or 50 nmol） significantly increased serotonin in DRN and hypothalamus, as well increased noradrenaline in locus coeruleus （LC） and hypothalamus. Immunohistochemistry study indicated that the application CaC12 （25 or 50 nmol） into the DRN significantly increased c-Fos expression ratio in wake-promoting neurons including seroton- ergic neurons in the DRN, noradrenergic neurons in the LC and orxinergic neurons in the perifornical nucleus （Pef） , but decreased c-Fos expression ratio of GABAergic sleep-promoting neurons in the ventrolateral preoptic nu- cleus （VLPO）. Conclusion These results suggest that Ca^2＋ in the DRN exert arousal effects via up-regulation of serotonergic function in endogenous sleep-wake regulating pathways.展开更多
OBJECTIVE Abnormal striatal dopaminergic and glutamatergic neurotransmis⁃sion is central to the pathophysiology of schizo⁃phrenia.In this study,we investigated the roles of M4 receptor interplay with D1 signaling in s...OBJECTIVE Abnormal striatal dopaminergic and glutamatergic neurotransmis⁃sion is central to the pathophysiology of schizo⁃phrenia.In this study,we investigated the roles of M4 receptor interplay with D1 signaling in stria⁃tal neurotransmission that affect glutamatergic transmission to control the etiology of neuropsy⁃chiatric disorders.METHODS To study dorsal striatum(DS)region-specific neuronal and behav⁃ioral responses modulated by M4 receptors,we used clustered regularly interspaced short palin⁃dromic repeats-associated protein 9 technology to generate mice lacking M4 in the dorsal stria⁃tum(DS-M4-KD).The M4 positive allosteric modu⁃lator,VU0467154,were used to study the phar⁃macologically profiles with M4 receptor stimula⁃tion in WT mice.Oxotremorine M(Oxo-M),a no subtype-selective muscarinic agonist,was used to show that mAchRs activation,in order to dissect the particular function of M4,in DS-M4-KD mice.Open filed test and forced swim test were used to assess the change of psychiatric-like behav⁃iors.Western blotting and immunohistochemistry were used to detect protein levels of phosphory⁃lation site of dopamine-and cAMP-regulated phosphoprotein of 32 ku(DARPP-32).Whole-cell patch-clamp recording was used to assess M4-mediated cholinergic inhibition of glutamater⁃gic synaptic input transmission.RESULTS West⁃ern blotting and immunohistochemistry assay showed VU0467154(5 mg·kg-1,ip)promoted phosphorylation of DARPP-32 at Thr75,and atten⁃uated D1-dependent phosphorylation of DARPP-32 at Thr34 within the mouse DS.Consistently,the Oxo-M(4μg,icv)also increased DARPP-32 phosphorylation at site Thr75 to reversed phos⁃phorylation at site Thr34 in WT mice,but not in DS-M4-KD mice.In parallel with altered DARPP-32 responses,VU0467154 or Oxo-M evoked a psychological stress response and reversed D1-induced hyperlocomotion in mice in open field test and force swim tests.However,Oxo-M sup⁃pression of D1-depengdeng behavioral respons⁃es was impaired in DS-M4-KD mice.Whole-cell patch recording showed that VU0467154 or Oxo-M mediated endogenous cholinergic inhibition of miniature excitatory postsynaptic currents through M4 receptors,which in turn suppressed D1-depen⁃dent glutamatergic synaptic transmission in the DS.CONCLUSION This study provides evidence for the role of M4 receptors in regulation of dopa⁃mine/DARPP-32 signaling and glutamate respons⁃es in the DS,and therefore modulation of psychi⁃atric behaviors associated with D1 signaling.This results indicate the mechanisms of treatments targeting M4 in psychiatric disorders.展开更多
为解决耕整播一体机作业过程中面临的土壤回填和碎土效果不佳,以及耕作阻力较大等问题,该研究基于鲨鱼背鳍的轮廓曲线设计了一种仿生直刃旋耕刀。通过高斯方程对背鳍轮廓进行拟合,结果显示拟合决定系数R2接近1且残差平方和SSE(sum of sq...为解决耕整播一体机作业过程中面临的土壤回填和碎土效果不佳,以及耕作阻力较大等问题,该研究基于鲨鱼背鳍的轮廓曲线设计了一种仿生直刃旋耕刀。通过高斯方程对背鳍轮廓进行拟合,结果显示拟合决定系数R2接近1且残差平方和SSE(sum of squares of the residuals)值接近0,验证了所用函数方程的优越性及数据预测的准确性。借助离散元仿真软件,以刀辊回转速度n、机具前进速度v和耕作深度h为因素,以回填率Pr、碎土率I和耕作阻力F为指标,进行二次正交旋转组合仿真试验。结果显示,当刀辊回转速度为241 r/min,机具前进速度为0.65 m/s,耕作深度为120 mm时,仿生旋耕刀-土壤颗粒接触模型具有最优解。室内土槽试验进一步验证,仿生旋耕刀回填率为84.34%,碎土率为79.7%,平均耕作阻力为87.25N,在同等运动参数条件下相较于直刃刀、弯形刀和凿形刀,回填率分别提升了11.98%、36.62%、23.2%;碎土率分别提升了15.07%、6.89%、10.32%;耕作阻力分别降低了15.59%、28.83%、24.38%,并且各指标与仿真结果的相对误差分别为3.7%、3.2%和4.5%,仿真试验和室内土槽试验结果表明仿生旋耕刀在减少耕作阻力的同时,可提高带状旋耕作业的回填率和碎土率,验证了设计的正确性。研究结果可为带状旋耕装置的研发与优化提供支撑。展开更多
Objective:Neuropathic pain(NP)is one of the most common forms of chronic pain,yet current treatment options are limited in effectiveness.Peripheral nerve injury activates spinal microglia,altering their inflammatory r...Objective:Neuropathic pain(NP)is one of the most common forms of chronic pain,yet current treatment options are limited in effectiveness.Peripheral nerve injury activates spinal microglia,altering their inflammatory response and phagocytic functions,which contributes to the progression of NP.Most current research on NP focuses on microglial inflammation,with relatively little attention to their phagocytic function.Early growth response factor 2(EGR2)has been shown to regulate microglial phagocytosis,but its specific role in NP remains unclear.This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP,with the goal of identifying potential therapeutic targets.Methods:Adult male Sprague-Dawley(SD)rats were used to establish a chronic constriction injury(CCI)model of the sciatic nerve.Pain behaviors were assessed on days 1,3,7,10,and 14 post-surgery to confirm successful model induction.The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR(RT-qPCR),Western blotting,and immunofluorescence staining.Adeno-associated virus(AAV)was used to overexpress EGR2 in the spinal cord,and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP.CCI and lipopolysaccharide(LPS)models were established in animals and microglial cell lines,respectively,and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays.After confirming the involvement of microglial phagocytosis in NP,AAV was used to overexpress EGR2 in both in vivo and in vitro models,and phagocytic activity was further evaluated.Finally,eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses to identify potential downstream effectors of EGR2.Results:The CCI model successfully induced NP.Following CCI,EGR2 expression in the spinal cord was upregulated in parallel with NP development.Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats.Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis,which was further amplified by EGR2 overexpression.Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation.Among them,Lag3 emerged as a potential downstream target of EGR2.Conclusion:EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.展开更多
目的:探讨经颅直流电刺激(transcranial direct current stimulation,tDCS)干预左背侧前运动皮质(dorsal premotor cortex,PMd)对高水平足球运动员运动疲劳后知觉预测能力的影响。方法:24名国家一级足球运动员在完成60%最大骑行功率(Pow...目的:探讨经颅直流电刺激(transcranial direct current stimulation,tDCS)干预左背侧前运动皮质(dorsal premotor cortex,PMd)对高水平足球运动员运动疲劳后知觉预测能力的影响。方法:24名国家一级足球运动员在完成60%最大骑行功率(Powermax)恒定负荷力竭骑行后,以平衡抵消法接受2 mA tDCS正极刺激左侧PMd 10 min和伪刺激,随后进行视觉搜索任务、预测足球突破过人任务和预测足球罚点球任务测试。结果:足球运动员疲劳后,进行tDCS正极刺激的视觉搜索任务反应时在3(P=0.039)和6(P=0.017)数量型与伪刺激相比显著降低,预测足球突破过人任务的准确率在240 ms条件与伪刺激相比显著增高(P<0.001)。但是视觉搜索任务准确性、预测足球突破过人任务的反应时以及预测足球罚点球任务的准确性和反应时在tDCS正极刺激条件和伪刺激条件之间没有显著差异。结论:tDCS正极干预左侧PMd 10 min能够有效改善高水平足球运动员运动疲劳后的知觉预测表现。tDCS可以作为有效工具在足球运动员运动训练和比赛中用以缓解疲劳造成的知觉预测能力下降。展开更多
作为祖国医学的重要组成部分,针刺与热灸等体表刺激在镇痛与调节内脏功能等方面发挥着不可替代的治疗效应。随着现代神经生理学、分子生物学及基因编辑技术等快速发展,研究者可通过不同生物标记技术探究既往无法区分的细胞亚型,为以分...作为祖国医学的重要组成部分,针刺与热灸等体表刺激在镇痛与调节内脏功能等方面发挥着不可替代的治疗效应。随着现代神经生理学、分子生物学及基因编辑技术等快速发展,研究者可通过不同生物标记技术探究既往无法区分的细胞亚型,为以分子标记物为切入点探究体表不同类型感受器介导针灸调节效应的作用机制提供了新的研究范式。然而,针对上述研究进展的系统归纳目前尚且缺如。鉴于此,本文综述了瞬时受体电位(transient receptor potential,TRP)离子通道家族、Mas相关G蛋白偶联受体(Mas related G protein-coupled receptor,MRGPR)家族等分子标记的C类多模态伤害感受器(C-polymodal nociceptor,CPN)在针灸镇痛及内脏调节中的作用效应及机制探讨,以期为针灸传入相关始动因素的分子特性及功能研究提供思路,亦为传统与现代医学的融合发展提供潜在探索方向。展开更多
文摘Aim Serotonergic neurons in the dorsal raphe nucleus （DRN） are involved in the control of sleep- wake states. Our previous study indicated that calcium （Ca^2＋ ） modulation in the DRN plays an important role in rapid eye movement sleep （REMS） and non-REMS （NREMS） regulation during pentobarbital hypnosis. Presentstudy was designed to investigate the effects of Ca^2＋ in the DRN on sleep-wake regulation and related neuronal mechanism in freely moving rats. Methods CaC12 （25 or 50 nmol） was microinjected into the DRN and sleep pa- rameters were detective by electroencephalogram （EEG） Monoamine neurotransmitters were detected by HPLC- ECD. c-Fos expression in sleep-wake regulating nucleus was detected by immunohistochemistry. Results Our re- sults showed that microinjection of CaC12 （25 or 50 nmol） into the DRN promoted wakefulness and suppressed NREMS including slow wave sleep （SWS） and REMS in freely moving rats. Meanwhile intro-DRN application of CaC12 （25 or 50 nmol） significantly increased serotonin in DRN and hypothalamus, as well increased noradrenaline in locus coeruleus （LC） and hypothalamus. Immunohistochemistry study indicated that the application CaC12 （25 or 50 nmol） into the DRN significantly increased c-Fos expression ratio in wake-promoting neurons including seroton- ergic neurons in the DRN, noradrenergic neurons in the LC and orxinergic neurons in the perifornical nucleus （Pef） , but decreased c-Fos expression ratio of GABAergic sleep-promoting neurons in the ventrolateral preoptic nu- cleus （VLPO）. Conclusion These results suggest that Ca^2＋ in the DRN exert arousal effects via up-regulation of serotonergic function in endogenous sleep-wake regulating pathways.
文摘OBJECTIVE Abnormal striatal dopaminergic and glutamatergic neurotransmis⁃sion is central to the pathophysiology of schizo⁃phrenia.In this study,we investigated the roles of M4 receptor interplay with D1 signaling in stria⁃tal neurotransmission that affect glutamatergic transmission to control the etiology of neuropsy⁃chiatric disorders.METHODS To study dorsal striatum(DS)region-specific neuronal and behav⁃ioral responses modulated by M4 receptors,we used clustered regularly interspaced short palin⁃dromic repeats-associated protein 9 technology to generate mice lacking M4 in the dorsal stria⁃tum(DS-M4-KD).The M4 positive allosteric modu⁃lator,VU0467154,were used to study the phar⁃macologically profiles with M4 receptor stimula⁃tion in WT mice.Oxotremorine M(Oxo-M),a no subtype-selective muscarinic agonist,was used to show that mAchRs activation,in order to dissect the particular function of M4,in DS-M4-KD mice.Open filed test and forced swim test were used to assess the change of psychiatric-like behav⁃iors.Western blotting and immunohistochemistry were used to detect protein levels of phosphory⁃lation site of dopamine-and cAMP-regulated phosphoprotein of 32 ku(DARPP-32).Whole-cell patch-clamp recording was used to assess M4-mediated cholinergic inhibition of glutamater⁃gic synaptic input transmission.RESULTS West⁃ern blotting and immunohistochemistry assay showed VU0467154(5 mg·kg-1,ip)promoted phosphorylation of DARPP-32 at Thr75,and atten⁃uated D1-dependent phosphorylation of DARPP-32 at Thr34 within the mouse DS.Consistently,the Oxo-M(4μg,icv)also increased DARPP-32 phosphorylation at site Thr75 to reversed phos⁃phorylation at site Thr34 in WT mice,but not in DS-M4-KD mice.In parallel with altered DARPP-32 responses,VU0467154 or Oxo-M evoked a psychological stress response and reversed D1-induced hyperlocomotion in mice in open field test and force swim tests.However,Oxo-M sup⁃pression of D1-depengdeng behavioral respons⁃es was impaired in DS-M4-KD mice.Whole-cell patch recording showed that VU0467154 or Oxo-M mediated endogenous cholinergic inhibition of miniature excitatory postsynaptic currents through M4 receptors,which in turn suppressed D1-depen⁃dent glutamatergic synaptic transmission in the DS.CONCLUSION This study provides evidence for the role of M4 receptors in regulation of dopa⁃mine/DARPP-32 signaling and glutamate respons⁃es in the DS,and therefore modulation of psychi⁃atric behaviors associated with D1 signaling.This results indicate the mechanisms of treatments targeting M4 in psychiatric disorders.
文摘为解决耕整播一体机作业过程中面临的土壤回填和碎土效果不佳,以及耕作阻力较大等问题,该研究基于鲨鱼背鳍的轮廓曲线设计了一种仿生直刃旋耕刀。通过高斯方程对背鳍轮廓进行拟合,结果显示拟合决定系数R2接近1且残差平方和SSE(sum of squares of the residuals)值接近0,验证了所用函数方程的优越性及数据预测的准确性。借助离散元仿真软件,以刀辊回转速度n、机具前进速度v和耕作深度h为因素,以回填率Pr、碎土率I和耕作阻力F为指标,进行二次正交旋转组合仿真试验。结果显示,当刀辊回转速度为241 r/min,机具前进速度为0.65 m/s,耕作深度为120 mm时,仿生旋耕刀-土壤颗粒接触模型具有最优解。室内土槽试验进一步验证,仿生旋耕刀回填率为84.34%,碎土率为79.7%,平均耕作阻力为87.25N,在同等运动参数条件下相较于直刃刀、弯形刀和凿形刀,回填率分别提升了11.98%、36.62%、23.2%;碎土率分别提升了15.07%、6.89%、10.32%;耕作阻力分别降低了15.59%、28.83%、24.38%,并且各指标与仿真结果的相对误差分别为3.7%、3.2%和4.5%,仿真试验和室内土槽试验结果表明仿生旋耕刀在减少耕作阻力的同时,可提高带状旋耕作业的回填率和碎土率,验证了设计的正确性。研究结果可为带状旋耕装置的研发与优化提供支撑。
基金supported by the National Natural Science Foundation of China(82071249 and 81771207).
文摘Objective:Neuropathic pain(NP)is one of the most common forms of chronic pain,yet current treatment options are limited in effectiveness.Peripheral nerve injury activates spinal microglia,altering their inflammatory response and phagocytic functions,which contributes to the progression of NP.Most current research on NP focuses on microglial inflammation,with relatively little attention to their phagocytic function.Early growth response factor 2(EGR2)has been shown to regulate microglial phagocytosis,but its specific role in NP remains unclear.This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP,with the goal of identifying potential therapeutic targets.Methods:Adult male Sprague-Dawley(SD)rats were used to establish a chronic constriction injury(CCI)model of the sciatic nerve.Pain behaviors were assessed on days 1,3,7,10,and 14 post-surgery to confirm successful model induction.The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR(RT-qPCR),Western blotting,and immunofluorescence staining.Adeno-associated virus(AAV)was used to overexpress EGR2 in the spinal cord,and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP.CCI and lipopolysaccharide(LPS)models were established in animals and microglial cell lines,respectively,and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays.After confirming the involvement of microglial phagocytosis in NP,AAV was used to overexpress EGR2 in both in vivo and in vitro models,and phagocytic activity was further evaluated.Finally,eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses to identify potential downstream effectors of EGR2.Results:The CCI model successfully induced NP.Following CCI,EGR2 expression in the spinal cord was upregulated in parallel with NP development.Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats.Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis,which was further amplified by EGR2 overexpression.Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation.Among them,Lag3 emerged as a potential downstream target of EGR2.Conclusion:EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
文摘目的:探讨经颅直流电刺激(transcranial direct current stimulation,tDCS)干预左背侧前运动皮质(dorsal premotor cortex,PMd)对高水平足球运动员运动疲劳后知觉预测能力的影响。方法:24名国家一级足球运动员在完成60%最大骑行功率(Powermax)恒定负荷力竭骑行后,以平衡抵消法接受2 mA tDCS正极刺激左侧PMd 10 min和伪刺激,随后进行视觉搜索任务、预测足球突破过人任务和预测足球罚点球任务测试。结果:足球运动员疲劳后,进行tDCS正极刺激的视觉搜索任务反应时在3(P=0.039)和6(P=0.017)数量型与伪刺激相比显著降低,预测足球突破过人任务的准确率在240 ms条件与伪刺激相比显著增高(P<0.001)。但是视觉搜索任务准确性、预测足球突破过人任务的反应时以及预测足球罚点球任务的准确性和反应时在tDCS正极刺激条件和伪刺激条件之间没有显著差异。结论:tDCS正极干预左侧PMd 10 min能够有效改善高水平足球运动员运动疲劳后的知觉预测表现。tDCS可以作为有效工具在足球运动员运动训练和比赛中用以缓解疲劳造成的知觉预测能力下降。
文摘作为祖国医学的重要组成部分,针刺与热灸等体表刺激在镇痛与调节内脏功能等方面发挥着不可替代的治疗效应。随着现代神经生理学、分子生物学及基因编辑技术等快速发展,研究者可通过不同生物标记技术探究既往无法区分的细胞亚型,为以分子标记物为切入点探究体表不同类型感受器介导针灸调节效应的作用机制提供了新的研究范式。然而,针对上述研究进展的系统归纳目前尚且缺如。鉴于此,本文综述了瞬时受体电位(transient receptor potential,TRP)离子通道家族、Mas相关G蛋白偶联受体(Mas related G protein-coupled receptor,MRGPR)家族等分子标记的C类多模态伤害感受器(C-polymodal nociceptor,CPN)在针灸镇痛及内脏调节中的作用效应及机制探讨,以期为针灸传入相关始动因素的分子特性及功能研究提供思路,亦为传统与现代医学的融合发展提供潜在探索方向。
