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In situ High-pressure NMR Observations on the Formation and Dissociation of Methane Hydrate

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Chinese Chemical Letters 2006年第6期17卷 791-794页

作者： Ai Bing CHEN Wei Ping ZHANG Xi Jie LAN Heng ZHENG xiu Mei liu xiu Wen HAN Xin He BAO State Key Laboratory of Catalysis Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023

A home-made static NMR cell with pressure up to 10 MPa was employed to observe the formation and dissociation processes of methane hydrate by in situ ^1H and ^13C NMR spectroscopies. Methane hydrate can be formed or decomposed in the temperature range of -5 to -13℃ at pressures between 4.0 and 7.0 MPa. The higher methane pressure, the formation or dissociation temperature of methane hydrate was higher. In situ ^1H NMR experiments indicated that the critical size of the hydrate clusters is crucial for the formation of methane hydrate.

关键词： In situ NMR high-pressure NMR methane methane hydrate hydrate formation,hydrate dissociation.

Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels

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Research 2023年第4期2023卷 739-753页

作者： Chu Tong Peng-Xiang Min Qian Zhang Ru-Xin Gu Yao-Hai Wen Yi Shi Yu-Huan Bao Xiang Chen Yi-Xuan Zhang Xing-Feng Mao Hao-Yang Yuan xiu-xiu liu Takuya Sasaki Li Zhang Feng Han Ying-Mei Lu Department of Physiology School of Basic Medical SciencesNanjing Medical UniversityNanjing211166China International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjing211166China Department of Geriatrics Nanjing Brain Hospital Affiliated to Nanjing Medical UniversityNanjing210029China Institute of Pharmacology and Toxicology College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Gusu School Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou215002China Department of Pharmacology Graduate School of Pharmaceutical SciencesTohoku UniversitySendai980-8578Japan Institute of Brain Science the Affiliated Brain Hospital of Nanjing Medical UniversityNanjing211166China.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like ***,the molecular mechanisms underlying this disturbance remain ***,we showed that cyclin-dependent kinase 5(Cdk5)was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing *** levels of CDK5 also decreased in patients with Parkinson’s disease accompanied by motor ***,Cdk5 deficiency in cholinergic neurons triggered paw tremors,abnormal motor coordination,and motor balance deficits in *** symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+channels(BK channels).Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient ***,CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of *** of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f ***,these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuronmediated motor function,providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.

关键词： Cdk5 Neuron CDK5

BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2490-2503页

作者： xiu-xiu liu Xing-Hui Chen Zhi-Wei Zheng Qin Jiang Chen Li Lin Yang Xiang Chen Xing-Feng Mao Hao-Yang Yuan Li-Li Feng Quan Jiang Wei-Xing Shi Takuya Sasaki Kohji Fukunaga Zhong Chen Feng Han Ying-Mei Lu Key Laboratory of Cardiovascular&Cerebrovascular Medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical University211166 NanjingChina Department of Physiology School of Basic Medical SciencesNanjing Medical University211166 NanjingChina Institute of Pharmacology and Toxicology College of Pharmaceutical SciencesZhejiang University310058 HangzhouChina Department of Pharmaceutical and Administrative Sciences Loma Linda University School of PharmacyLoma LindaCA 92350USA Department of Basic Sciences Loma Linda University School of MedicineLoma LindaCA 92350USA Department of Pharmacology Graduate School of Pharmaceutical SciencesTohoku UniversitySendai 980-8578Japan Institute of Brain Science the Affiliated Brain Hospital of Nanjing Medical University210029 NanjingChina Gusu School Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical University215002 SuzhouChina

Cerebellar ataxias are characterized by a progressive decline in motor coordination,but the specific output circuits and underlying pathological mechanism remain poorly *** cell-type-specific manipulations,we discovered a novel GABAergic Purkinje cell(PC)circuit in the cerebellar IV/V lobe that projected to CaMKIIα+neurons in the fastigial nucleus(FN),which regulated sensorimotor ***,transcriptomics profiling analysis revealed various cerebellar neuronal identities,and we validated that biorientation defective 1(BOD1)played an important role in the circuit of IV/V lobe to ***1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs,accompany with ataxia ***,BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα+neurons in the FN and ameliorated ataxia behaviors in L7-Cre;BOD1f/f ***,these findings further suggest that specific regulation of the cerebellar IV/V lobePCs→FNCaMKIIα+circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.

关键词： fastigial reversed Together

Pharmacologic inhibition GLT-1 degradation by Ceftriaxone as an effective therapy for epilepsy

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Pharmacologic inhibition GLT-1 degradation by Ceftriaxone as...

2023年全国心血管药理学学术会议

作者： xiu-xiu liu Ying-mei Lu Feng Han Key Laboratory of Cardiovascular & Cerebrovascular Medicine School of PharmacyNanjing Medical University Department of Physiology School of Basic Medical SciencesNanjing Medical University

Epilepsy is one of the most common chronic neurological diseases,which is believed to be caused by an imbalance of synaptic excitation and *** is the principal excitatory neurotransmitter in the central nervous *** glutamate transport GLT-1（EAAT2;slc1a2） is predominantly expressed in astrocytes and responsible for maintaining low extracellular glutamate ***-transporter impairment in astrocytes directly contributes to the *** we report that selective knockout of endothelial Cdk5 increased the excitability of hippocampal neurons,trigged spontaneous hippocampal epileptic discharges in Cdh5-Cre;Cdk5 *** effect was associated with a decrease in GLT-1 function in astrocytes that impairs glutamate homeostatic functions,which can contribute to neuronal hyperexcitability and seizure ***（CEF） restored astrocytic GLT-1 function and inhibited seizures in endothelial Cdk5-deficient *** this study,we explored the role of GLT-1 in epilepsy and demonstrated that pharmacologic activation GLT-1 by Ceftriaxone is a promising therapeutic strategy for epilepsy and related neurodegenerative *** results reveal a previously unknown link between vascular dysfunction and epilepsy and suggest that endothelial Cdk5 regulates astrocyte GLT-1 and early treatment with ceftriaxone showed antiepileptic ***:We generated three sets of conditional endothelial-specific Cdk5 knockout mice (Cdh5-Cre;Cdk5 mice,Cdh5-CreERT2;Cdk5 mice,BR1-iCre-Cdk5 mice) to investigate whether Ceftriaxone can restore astrocytic GLT-1 function in endothelial Cdk5-deficient *** behavioral phenotypes were detected by 24-hour video surveillance and EEG *** concentration of excitatory neurotransmitter was detected by in vivo microdialysis *** role of endothelial Cdk5 on the GLT-1 function of hippocampal astrocytes was assessed by patch clamp *** signaling mechanisms between endoth

关键词： Cdk5 Endothelial Cells Astrogliosis GLT1 Ceftriaxone

Characterization of cyclophilin D in freshwater pearl mussel (Hyriopsis schlegelii)

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Zoological Research 2017年第2期38卷 103-109页

作者： xiu-xiu liu Cheng-Yuan Wang Chun Luo Jun-Qing Sheng Di Wu Bei-Juan Hu Jun-Hua Wang Yi-Jiang Hong School of Life Sciences Nanchang University Nanchang Jiangxi 330031 China Key Laboratory of Aquatic Animals Resources and Utilization of Jiangxi Nanchang University Nanchang Jiangxi 330031 China

Cyclophilin D （referred to as HsCypD） was obtained from the freshwater pearl mussel （Hyriopsis schlegelil）. The full-length cDNA was 2 671 bp, encoding a protein consisting of 367 amino acids. HsCypD was determined to be a hydrophilic intracellular protein with 10 phosphorylation sites and four tetratricopeptide repeat （TPR） domains, but no signal peptide. The core sequence region YKGCIFHRIIKDFMVQGG is highly conserved in vertebrates and invertebrates. Phylogenetic tree analysis indicated that CypD from all species had a common origin, and HsCypD had the closest phylogenetic relationship with CypD from Lottia gigantea. The constitutive mRNA expression levels of HsCypD exhibited tissue-specific patterns, with the highest level detected in the intestines, followed by the gonads, and the lowest expression found in the hemocytes.

关键词： Hyriopsis schlegelii Cyclophilin D Sequence analysis

Endothelial Cdk5 deficit leads to the development of spontaneous epilepsy through CXCL1/CXCR2-mediated reactive astrogliosis

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Endothelial Cdk5 deficit leads to the development of spontan...

2019中国生理学会学术年会暨张锡钧基金第十五届全国青年优秀生理学学术论文交流会及第十三届全国青年生理学工作者学术会议

作者：卢应梅 xiu-xiu liu Lin Yang Ling-Xiao Shao Department of Physiology Nanjing Medical University Institute of Pharmacology and Toxicology College of Pharmaceutical SciencesZhejiang University

Aim: Blood-brain barrier(BBB) dysfunction has been suggested to play an important role in ***, the mechanism mediating the transition from cerebrovascular damage to epilepsy remains *** targeting the underlying mechanism of this imbalance may prove to be more effective than current antiepileptic ***: Here, endothelial tamoxifeninducible driver Cdh5-CreERT2;Cdk5 f/f mice were used for following *** seizure activity was monitored by EEG *** assess BBB permeability, fluorescence tracers with different molecular size from small to large including biocytin-tetramethylrhodamine was intravenous injected via the tail vein *** Electrophysiological characteristics of pyramidal neurons and astrocytes were performed by whole-cell patch-clamp ***:Here, we report that endothelial cyclin-dependent kinase 5(CDK5) is a central regulator of neuronal ***-specific Cdk5 knockout led to spontaneous seizures in *** mice showed increased endothelial chemokine(C-X-C motif) ligand 1(CXCL1) expression,decreased astrocytic glutamate reuptake through the glutamate transporter 1(GLT1), and increased glutamate synaptic *** restored astrocytic GLT1 function and inhibited seizures in Cdk5–deficient mice, and these effects were also reversed after silencing CXCL1 in endothelial cells and CXCR2 in astrocytes respectively in the CA1 by AAV ***: Our findings reveal a previously unknown function of the endothelialderived Cdk5 signaling in the *** Cdk5 deficiency induces spontaneous epilepsy in an age-dependent *** effect is associated with a decrease in GLT1 mediated glutamate uptake and an increase in excitability of hippocampal pyramidal *** evidence further suggests that these effects depend on CXCL1 release from ECs and subsequent activation of astrocytic CXCR2 receptors by ***,we found that these

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan liu Zi-Ling Shi Quan-Hong Ma Department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice

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Endothelial ErbB4 deficit induces alterations in exploratory...

中国神经科学学会第十二届全国学术会议

作者： Gang Wu xiu-xiu liu Nan-Nan Lu Feng Han Ying-Mei Lu Institute of Pharmacology and Toxicology College of Pharmaceutical SciencesZhejiang University School of Medicine Zhejiang University City College

ErbB4 is a key member of the Erb B receptor tyrosine kinase(RTK) family, is present throughout the primate brain and has a distinct functional profile. Here, we use a combination of endothelial-specific gene-knockdown and neurochemical strategies investigate changes in neurobehavioral features and the potential underlying mechanisms. The endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice, however, the water maze task for spatial memory and the memory reconsolidation test reveal no changes. Additionally, we observe no impairment in Ca MKII phosphorylation in Cdh5 Cre;ErbB4 mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro positron emission tomography, is observed in the Cdh5 Cre;ErbB4 mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1(Ser555) and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Together, targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders.

关键词： ErbB4 endothelial exploratory behavior brain energy metabolism

Mozart and invert-mozart music effect:enhancement and impairment of spatial memory in developing rats

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Mozart and invert-mozart music effect:enhancement and impair...

中国神经科学学会第十届全国学术会议

作者： xiu-xiu liu Yin QING Ying-Shou XING Mao-Seng WANG Yang XIA De-Zhong YAO Key Laboratory for NeuroInformation of Ministry of Education University of Electronic Science and Technology of China

Objective Mozart music has been suggested to have a beneficial effect on various types of performance in ***,the physiological and molecular mechanism of this effect still remains *** We studied the spatial cognitive ability in developing rats after early different music exposure,including classical Mozart’s K.448,invert-Mozart’s K.448（entirely reversed Mozart music sequence）,modulated Mozart music retaining pitch or rhythm element *** expressing level of brain-derived neurotrophic factor（BDNF） and its receptor,tyrosine kinase receptor B（TrkB） and the neurogenesis were investigated for the rats with Mozart’s K.448 and invert-Mozart’s K.448 *** The results showed that early exposure to Mozart music enhanced spatial learning and memory ***,increased the neurogenesis of dentate gyrus and the BDNF expressing level of ***,the rhythm element of Mozart music facilitated learning ability more than pitch *** contrast,exposure to invert-Mozart music impaired the spatial learning and memory ability and reduced the neurogenesis of dentate gyrus and the BDNF expressing level of *** Our findings demonstrate that music exposure during the early life may induce long-term plastic changes of central nervous system by modulating the neurogenesis and up-regulating BDNF level,which,in turn,may regulate the ability of learning and *** may be a determinative factor of music inducing the positive or negative effect.

关键词： Mozart effect rhythm BDNF neurogenesis spatial cognitive ability