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Cognitive impairment and expression of GFAP in diabetes rats and influence of insulin therapy

Cognitive impairment and expression of GFAP in diabetes rats...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yong-Zhong LIN~1,Yu JIAO~1,Min WU~1,Jin WANG~2,Chang-Kai SUN~(2,*) 1 Department of Neurology,The Second Affiliated Hospital of Dalian Medical University,Dalian 116027,China 2 Institution of Brain Disease of Dalian Medical University,Dalian 116027,China

Objective To investigate cognitive impairment and astrocytes reaction in diabetic rats and the influence of the insulin *** 52 health grown-up male Sprague-Dawley(SD) rats ware divided into 2 big groups stochastically:1-month group(n=26) and 3-month group(n=26);Each group then divided into 3 groups stochastically: diabetic group(n=10),insulin treatment group(n=10) and control group(n=6).Streptozotocin-induced diabetic model rat(60 mg/kg) was *** the insulin treatment group,the rats were treated with isophane insulin everyday(2-3 U/day) based on blood glucose *** of Morris water maze were taken place 1 month and 3 months later respectively,after which slices taken from hippocampus,basal ganglia,the white matter nearby lateral ventricle and frontal lobe were used to immunohistochemistral *** expression of GFAP positive cells was observed in diabetic ***(1) Spatial study and memory ability *** with control group,the swimming incubation period was prolonged in 3 month insulin treatment group(PO.05) and diabetic group including both 1-month(PO.05) and 3-month groups(PO.05),while that of 1-month insulin treatment group was not prolonged.(2) Compared with control group,the change of GFAP expression in different sites of brain was not significant in 1-month diabetic group and insulin treatment group including 1-month and 3-month *** in 3-month diabetic group the number of GFAP positive cells was more than control group in basal ganglia(P<0.05) and white matter nearby lateral ventricle (P<0.05).The number of GFAP positive cells in 3-month insulin treatment group was less than diabetic group in basal ganglia(P<0.05) and white matter nearby lateral ventricle(P<0.05).Conclusion(1) Diabetic rats present learning and memory dysfunction at 1st month.(2) The astrocytes change doesn't appear with early cognitive impairment in diabetic rats,suggesting cognitive impairment is not caused by astrocytes change.T

关键词： cognitive impairment diabetes GFAP insulin

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Neuregulinl represses limbic epileptogenesis via activation of ErbB4 signaling in parvalbumin-positive interneurons

Neuregulinl represses limbic epileptogenesis via activation ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Guo-He TAN~(1,★),Yuan-Yuan LIU~(1,★),Xiao-Ling HU~1,Dong-Min YIN~2,Lin MEI~(2,*),Zhi-Qi XIONG~(1,*) 1 Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031,China 2 Program of Developmental Neurobiology and Department of Neurology,Institute of Molecular Medicine and Genetics,Georgia's Health Sciences University,Augusta,GA 30912,USA

Objective Epilepsy is a common and refractory neurological disorder that affects l%-2%worldwide people,but the neuronal regulatory mechanisms of epileptogenesis remain largely ***-dependent expression of polypeptide growth factors has been implicated in epileptogenesis;however,little is known about factors that may act as intrinsic,homeostatic or counter-balancing *** this study,we investigated the role of a growth factor neuregulin 1（NRG1） and its ErbB4 receptor in limbic *** Two classical models of limbic epilepsy,kindling and pilocarpine models,were used to investigate the expression pattern of NRG1 and ErbB4. Using lose- and gain- of- function strategies,we determined the role of NRG1/ErbB4 signaling in epileptogenesis pharmacologically and ***/loxP-mediated cell-specific mutation was employed to identify the specific cellular mechanism underlying the effect of this signaling in limbic ***（1） Limbic seizure activity increased the expression of Nrg1 and phosphorylation of ErbB4 receptor in the brain.（2） In kindling model, epileptogenesis was inhibited by intracerebral infusion of recombinant NRG1,but exacerbated by neutralizing endogenous NRG1 with soluble ecto-ErbB4.（3） Pharmacologically,inhibition of ErbB4 activity with PD158780 greatly promoted kindling-induced epileptogenesis.（4） Genetically,heart-rescued ErbB4 knockout mice exhibited accelerated progression of the kindling effect.（5） Specific depletion of ErbB4 in parvalbumin（PV）-positive GABAergic interneurons resulted in accelerated kindling ***,NRG1 infusion failed to suppress kindling development in PV-Cre;ErbB4 mice.（6） Deletion of ErbB4 in CaMKIIα-positive pyramidal neurons was ineffective for epileptogenesis,as evidenced by normal kindling progression of both CaMKIIα-iCre;ErbB4 and CaMKIIα-CreER;ErbB4 mice.（7） Ablation of ErbB4 in PV-positive neurons increased kindling-induced brain hyperexcitability and spo

关键词： limbic epilepsy epileptogenesis neuregulin 1 ErbB4 parvalbumin-positive interneurons

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Modulation of neuron Navl.2 channel by sigma-1 receptor agonist

Modulation of neuron Navl.2 channel by sigma-1 receptor agon...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xiao-Fei GAO,Chang-Long HU,Yan-Ai MEI~* Institutes of Brain Science,School of Life Sciences and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200433,China

Objective It has been shown that sigma-1 receptor modulated many biological function and play an important role in neuron signal *** Sigma-1 receptor widely expressed in central nervous system and periphery,the modulation of neuron Na channel isoforms by sigma-1 receptor has not been examined in detail. The present study is to explore the mechanism of neuron Nav1.2 channel modulation by sigma-1 *** Here,we investigated the effects of（+）-SKF 10047,a sigma-1 receptor specific agonist,on rat Navl.2 channel heterogenously expressed in human embryonic kidney cell line 293T *** currents of Navl.2 channel was recorded by whole-cell patch ***（1）100μM（+）-SKF 10047 significantly inhibits the Navl.2 current by 40%.（+）-SKF 10047-induced inhibitory effect on rNaV1.2 current was fast and reversible.（2）In addition to inhibiting the rNav1.2 current amplitude,（+）-SKF 10047 significantly accelerated the inactivation of rNav1.2 channels and shifted the steady-state inactivation curve toward to hyperpolarizing potential.（3）BD 1047,a sigma-1 receptor antagonist reduced the inhibitory effect on rNavl.2 current induced by（+）-SKF 10047.（4）Blocking PKA or PKC pathway by the conventional blockers H-89 or（Go6976）did not modified the effect of（+）-SKF 10047 on rNaV1.2 current.（5）Inhibiting Gas and Gai with NF 449 and NF 023,or by cholera toxin（CTX）and pertussis toxin（PTX）, also did not significantly changed the inhibitory effect of（+）-SKF 10047 on rNaV1.2 *** These results suggested that G-protein coupling receptor or PKA and PKC pathway was not associated with the effect of （+）-SKF 10047 on rNavl.2 *** the effect of（+）-SKF 10047 on rNavl.2 current operate through sigma-1 receptor or channel protein interactions will require further investigations.

关键词： rNav1.2 channel σ-1 receptor agonist (+)-SKF 10047 PKA PKC

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Activation of ATP-sensitive potassium channels enhances DMT1mediated ferrous iron uptake in SK-N-SH cells

Activation of ATP-sensitive potassium channels enhances DMT1...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xi-Xun DU,Hua-Min XU,Ning SONG,Hong JIANG,Jun-Xia XIE~* Department of Physiology,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:Physiology,Medical College of Qingdao University,Qingdao 266071,China

Objective Elevated iron accumulation has been reported in the substantia nigra（SN） in Parkinson's disease（PD）.Our previous study observed that increased levels of the iron importer divalent metal transporter 1（DMTl） were involved in this nigral iron accumulation and dopaminergic neurons loss in *** iron transport function of DMTl is also related to the membrane potential level,which increases with hyperpolarization of the cell membrane. Activation of ATP-sensitive potassium(K) channels,which could induce hyperpolarization of nigral dopaminergic neurons,is reported to be involved in the selective loss of these neurons in *** present study is to investigate whether activation of K channels could change the iron uptake function of *** DiBAC4（3） and calcein were used to detect membrane potential and ferrous iron *** iron concentration was measured using an inductively coupled plasma（ICP-2） *** transmembrane potential（△Ψm） and reactive oxygen species（ROS） were measured by flow cytometry using rhodamine123 and ***（1） When treated with diazoxide,a novel K channel opener,the membrane potential of SK-N-SH cells showed hyperpolarization.（2） The influx of ferrous iron and the intracellular iron levels were observed dramatically increased When the cells were co-incubated with diazoxide and ferrous iron,resulting in a decreased△Ψm and an elevated level of ROS production.（3） When treated with diazoxide,cells overexpressing SUR1 and Kir6.2 showed increased ferrous iron influx compared with the vector control,which induced a decrease in△Ψm and an increase in ROS production. Conclusion These results suggest that the activation of the K channels could enhance DMT 1-mediated ferrous iron uptake,leading to increase intracellular oxidative stress.

关键词： divalent metal transporter 1 iron ATP-sensitive potassium Parkinson's disease

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The effect of estrogen receptor alpha36 involved in neuroprotection of estrogen

The effect of estrogen receptor alpha36 involved in neuropro...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Wei ZOU~(1,2,*),Yi-Ni MA~1,Dan-Nv HAN~1,Ping ZOU~3,Hui-Fang HUANG~1 1 College of Life Science 2 The Research Center of Developmental and Educational Psychology,Liaoning Normal University,Dalian 116029, China 3 Teacher's College of Dalian University,Dalian 116622,China

Objective Estrogen（E）has a wide neuroprotective effect on central nervous system（CNS）which related to the signaling transduction mediated by estrogen receptor（ER）.However,the mechanism of different subtypes of ER involved in the process is still *** it was proved that ERα36,a variant of estrogen receptor-α,can respond to both estrogen and anti-estrogen stimuli via activation of the mitogen-activated protein kinase extracellular signal-regulated kinase signaling pathway and promote cell *** In this study,we detected the expression and distribution of ERα36 in PC12 cells,hippocampal neurons,cortical neurons and glial *** we study the expression pattern of ERα36 in mouse brain of different development stages and the relationship between the brain *** that ERα36 gene silencing PC12 cell model（PC12-36L）was ***,we study the effect of ERα36 low expression on E pretreated PC12 apoptosis induced by MPP in order to study the effect of ERα36 in membrane initiated estrogen signal pathway in neuron growth and apoptosis and provide a theoretical basis to illustrate the mechanism of membrane initiated estrogen signal pathway in *** The results shows that: （1）ERα36 was widely expressed in different regions of mouse brain and neuron cells;and increased with age in the cortex;（2）The cell model of ERα36 low expression（PC12-36L1）was successfully established by siRNA technology;（3）MPPtreatment induced apoptosis and inhibit Akt expression but activated P38 protein both PC12 cell and PC12- 36L1 *** the survival rate of PC12-36L1 cell was higher than that of PC12 cell;（4）When pretreatment with E for 1 h followed by MPP,the survival rate in ERα36 gene silencing cells is higher than that of in the parental cells. Conclusion It is suggested that ERa36 gene silencing can reduce PC12 apoptosis induced by MPPand ERα36 may play an important role in the neuroprotective effect of E.

关键词： ERα36 neuron estrogen MPP+ apoptosis

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The essential role of dopaminergic system in the food-anticipatory activity in mice

The essential role of dopaminergic system in the food-antici...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yuan-Yuan LIU~1,Tian-Ya LIU~2,Zong-Yuan HONG~2,Wei-Min QU~1,Zhi-Li HUANG~(1,*) 1 Department of Pharmacology,State Key Laboratory of Medical Neurobiology,Shanghai Medical College,Institute of Brain Science,Fudan University,Shanghai 200032,China 2 Institute of Quantitative Pharmacology,Department of Pharmacology,Wannan Medical College,Wuhu 241001, China

Objective When food is available during a restricted and predictable time of the day,mammals exhibit food-anticipatory activity（FAA）,a daily increase in locomotor activity preceding the presentation of *** many studies attempted to locate the food-entrainable circadian oscillator in the central nervous system,the mechanisms for FAA are a matter of *** present study was designed to clarify the role of dopaminergic and histaminergic systems in *** The mice were given access to food for 2 h（CT19-CT21） in ICR mice and for 4 h（CT 17-CT21） in gene-manipulated *** was monitored by infrared locomotor activity sensors and defined as the locomotor activity occurred 2 h before the availability of *** D,receptor（R）,D2R,and histamine H,R-specific antagonists,and DR- and HR-knockout（KO） mice were used to clarify the role of dopamine and histamine receptors in FAA induced by food restriction（FR）.In addition,brain monoamine concentrations on the 14 day of FR were determined by *** Pretreatment with DR antagonist SCH23390 at 1,3,or 10μg/kg significantly decreased FAA by 19%,26%or 19%,respectively,and DR antagonist raclopride at 22,67,or 200μg/kg significantly decreased FAA by 16%,36%or 41%,respectively,as compared with vehicle ***,co-administration of SCH23390 and raclopride synergistically inhibited FAA by 57%.Consistently,the levels of dopamine and its metabolites in the striatum and midbrain were significantly increased during FR-induced FAA,even in the mice pretreated with DR and DR ***,DR KO mice exhibited attenuated ***,pretreatment with pyrilamine at 2.5,5,or 10 mg/kg did not significantly decrease FAA,although it decreased the locomotor activity during the dark period in ad libitum mice,and H,R KO did not affect *** These results strongly indicate that dopaminergic system plays an essential role in the food-anticipatory activity in mice.

关键词： antagonist dopamine D1 receptor D2 receptor food restriction histamine H1 receptor food-anticipatory activity

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Extensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia:Morphological and covariation study

Extensive brain structural network abnormality in first-epis...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Siew E Chua Charlton Cheung Grinne M.McAlonan Pak C Sham David A Collier Marco Picchioni Stefania Benetti Andrea Mechelli Nicolas Crossley Joseph P.Kambeitz Paul Allen Philip McGuire Department of Psychiatry The University of Hong KongPokfulamS.A.R.China MRC SGDP Centre Institute of PsychiatryKing's College LondonLondon SE5 8AFUK Division of Psychological Medicine and Psychiatry Section of NeuroimagingInstitute of PsychiatryKing's College LondonLondon SE5 8AFUK St Andrew's Academic Centre Institute of PsychiatryKing's College LondonNN1 5BG Department of Psychosis Study Institute of PsychiatryKing's College LondonLondon SE5 8AFUK

Objective With a particular focus on putative cortico-striatal-thalamic-cortical(CSTC) networks current study aimed to explore robust gray matter volume(GMV) changes in non-medicated first-episode schizophrenia(FES) *** High-resolution T1-weighted images were obtained using 3.0 Tesla magnetic resonance imaging from 86 first-episode drug-naive schizophrenia patients and 86 healthy controls(CON).Severity of symptoms in patients was evaluated by using Positive and Negative Syndrome Scale(PANSS).Fourteen spherical region of interest (ROI) GMV in the CSTC loop were acquired after optimized voxel-based morphometry(VBM) *** of Spherical ROIs and corresponding correlation coefficients were compared between FES and CON *** associations of GMV with PANSS subscale score and symptom dimension scores were also *** GMV reduction was detected in bilateral hippocampus in FES group by VBM *** located in left inferior frontal gyrus(Brodmann's area 47) and right thalamus(medial dosal nucleus) present GMV *** of ROIs revealed more extensive GMV loss and disassociation between *** Our study support that schizophrenia involves distributed rather than focal pathology and disordered *** analysis could make compensation to VBM and ROI method to uncover more subtle aberrations in regional correlation.

关键词： Extensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia:Morphological and covariation study

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Effects of NR2A overexpression on prefrontal synaptic plasticity and prefrontal cortex-related memory

Effects of NR2A overexpression on prefrontal synaptic plasti...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yan-Hong DUAN,Wen SI,Jing MA,Bo WANG,Xiao-Hua CAO~* Shanghai Institute of Brain Functional Genomics,Key Laboratories of MOE and STCSM,East China Normal University,Shanghai 200062,China

Objective N-methyl-D-aspartate receptors(NMDARs) play an important role in learning and memory. NR2A and NR2B subunits are predominant in the prefrontal *** growing evidence implicates that specific subunit-containing NMDARs correlate with subsequent modifications of synaptic plasticity,whether the upregulation of NR2A subunit influences prefrontal synaptic plasticity and prefrontal cortex-related memory is not yet *** In the present study,we combined electrophysiological technique and behavioral method to investigate effects of NR2A overexpression on prefrontal synaptic plasticity and prefrontal cortex-related memory. Results(1) Western blotting results showed that the level of NR2A,but not NR2B protein,was significantly higher in prefrontal cortex of the transgenic mice than wild type mice.(2) Whole cell Patch-clamp recording showed that the ratio of NR2A/NR2B current increased significantly in transgenic mice compared with that in wide type mice;the decay time of evoked NMDAR-EPSC was sharply faster in transgenic mice than in wide type ***,the rise time of evoked NMDAR-EPSC in transgenic mice did not differ significantly from wide type mice.(3) Field potential recording showed that no significant differences were measured in basal synaptic transmission between transgenic mice and wide type mice;however,both prefrontal long-term potentiation(LTP) and long-term depression(LTD) were impaired in transgenic mice.(4) Behavioral tests showed that NR2A transgenic mice exhibited impaired prefrontal cortex-related working memory and reverse learning in the modified water maze and water maze reverse learning task. Conclusion NR2A/NR2B ratio increasing by NR2A overexpression can shorten the decay time of NMDAR-EPSC and impair prefrontal bidirectional synaptic plasticity and prefrontal cortex-related memory.

关键词： NMDA receptor NR2A subunit prefrontal cortex synaptic plasticity learning and memory

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Variations of ionotropic glutamate receptors mediating epileptiform activity in rat hippocampal CA1 region

Variations of ionotropic glutamate receptors mediating epile...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Bin-Sheng WANG,Zhu-Yan YOU,Min XIE,Zhen LI,Lie-Cheng WANG~* Department of Physiology,School of Basic Medical Science,Anhui Medical University,Hefei 230027,China

Objective The epileptiform activity was induced by perfusing GABAA receptor antagonist bicuculline (Bic,30μmol/L)in normal hippocampal slices and temporal lobe epilepsy(TLE)model was established by kainic acid(KA)injected into the center site of right hippocampus CA3 region with the stereotaxic *** investigate the variations of ionotropic glutamate receptors mediating epileptiform activity in rat hippocampal CA1 region by using extracellular recording in hippocampal slices,and to explore the mechanism of epileptogenesis. Methods Population spike(PS)was recorded in CA1 pyramidal cell layer by stimulating the Shaffer collaterals in stratum radiatum using extracellular field-potential ***(1)Single PS was usually recorded in normal pyramidal cell layer of hippocampal CA1 *** normal hippocampal slices with Bic(30μmol/L)could induce multiple epileptiform discharges,in which the PS number was(5.07±0.30,n=11),the amplitude of the first PS was increased significantly by(150.86±22.56)%(n=11,P<0.01)compared with the *** discharges could recorded in slices of TLE model rats,the PS number was(6.12±0.33,n=9).The PS number was increased significantly in slices of epileptiform activity compared with the control(P<0.01).(2)Variations of ionotropic glutamate receptors mediating PS in hippocampal CA1 *** PS recorded in normal pyramidal cell layer of hippocampal CA1 mainly mediated by non-NMDA *** PS recorded in normal slices after perfusing with Bic was partially mediated by NMDA receptor in addition to non-NMDA *** perfusing with NMDA receptor antagonist,APV(50μmol/L),the amplitude of the first PS was not significantly affected(n=11,P>0.05), however,the amplitude of the fourth and fifth PS was decreased obviously(n=11,P<0.05;n=9,P<0.05).After perfusing APV in slices of TLE model rats,the amplitude of the first PS was not significantly affected(n=9,P>0.05), but the amplitude of the fourth and fifth PS w

关键词： epilepsy hippocampus population spike receptor

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Receptor mechanism underlying the orexin-induced excitation on cerebellar interpositus nucleus neurons in rats at different ages

Receptor mechanism underlying the orexin-induced excitation ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yong-Hui WU,Qian-Xing ZHUANG,Jun ZHANG,Jing-Ning ZHU~*,Jian-Jun WANG~* Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Mailbox 426,Nanjing University,22 Hankou Road,Nanjing 210093,China

Central orexinergic system,which originates solely from the hypothalamus but projects almost the whole brain,has been traditionally implicated in regulation of many nonsomatic basic functions,such as sleep/wake cycle, feeding behavior,emotion,pain,and ***,its functions on motor control are seldom investigated. Interestingly,our previous studies have revealed an excitatory effect of orexin on neurons in the cerebellar interpositus nucleus（IN）,one of the final outputs of spinocerebellum coordinating body and limb movements,in adult rats. Thus,in the present study,receptor mechanism underlying the orexin-induced excitation on cerebellar IN neurons in rats,particularly at three key stages of development of cerebellar circuitry（7-14 days,21-28 days,and adult）,were ***,real-time RT-PCR results showed that both orexin 1 receptors（OX1Rs）and orexin 2 receptors （OX2Rs）are existed in the rat IN at all three different ***,by using brain slice preparations and extracellular recordings,effect of orexin and orexinergic agents on IN neurons were *** results showed that orexin-A（300 nM）excited the IN neurons at all three developmental stages（n=29,24,and 33,respectively）.Moreover,the orexin-induced excitation on IN neurons was not only partly blocked by selective OXR antagonist SB334867（1,3,10μM） in a dose-dependent manner,but also dose-dependently mimicked by selective OXR agonist[Ala,D-Leu]-orexin-B （300 nM and 1μM）at all three ages（n=9,10,8;and n=15,13,14,respectively）,indicating that both OXR and OXR mediate the orexin-induced excitation on IN neurons which does not change with ***,both the increase of excitatory response elicited by orexin-A or[Ala,D-Leu]-orexin-B and the antagonistic effect induced by SB334867 on IN neurons did not change along with development,although the basic spontaneous firing rate of IN neurons increases with *** these results demonstrate a consistent excitatory effect of orexin on IN neuron

关键词： orexin Receptor mechanism underlying the orexin-induced excitation on cerebellar interpositus nucleus neurons in rats at different ages

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