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Expression of iron-related proteins and alterations in iron content in the temporal cortex of parkinsonian patients

Expression of iron-related proteins and alterations in iron ...

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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-Jun YU,Ting-Ting DU,Ning SONG,Qing HE,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 It has been reported that iron increases in single DAergic neurons in the substantia nigra(SN) of postmortem parkinsonian patients,indicating that primary changes in neuronal iron could lead to neurodegeneration in Parkinson's disease(PD).However,the mechanism underlying this selective iron accumulation is largely unknown. Our previous studies in PD animal models showed iron import protein divalent metal transporter 1(DMT1) and iron export protein ferroportinl(Fpl) were all involved in the nigral iron *** the present study,we investigated the expression of iron-related proteins(DMT1,Fpl and IRP1) and alterations in iron content in the temporal cortex of postmortem parkinsonian *** Iron concentration was measured by an inductively coupled plasma(ICP-2) *** expression levels of IRP1,DMT1 and Fpl were determined by western blots. Results The iron levels were significantly lower in PD patients than that of age-matched *** expression levels of DMT 1,Fpl and IRP1 were decreased in temporal cortex of PD *** This is the first time to investigate the involvement of pallium's iron metabolism in the brains of PD *** results suggest that there might be a redistribution of iron in PD brains,especially between temporal cortex and SN.

关键词： Temporal cortex iron Parkinson's disease divalent metal transporter1 ferroportin1

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Inhibition of experimental myopia by a dopamine agonist:an understanding of different effectiveness between form deprivation and hyperopic defocus in guinea pigs

Inhibition of experimental myopia by a dopamine agonist:an u...

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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： Mark D.P.WILLCOX School of Optometry and Vision Science The University of New South WalesSydneyNSWAustralia

Objective The dopamine(DA)system in the retina is critical to normal visual development as lack of retinal DA signalling may contribute to myopic *** involvement of DA in myopic development is complex and may be different between form deprivation and hyperopic *** study aims to explore the possible different roles of DA signaling between the FDM and defocus-induced myopia using guinea *** This study evaluated effects of a non-selective DA receptor agonist,apomorphine(APO)on refractive development in guinea pigs treated with form deprivation or hyperopic defocus(from age of 21 to 32 days).Changes in retinal concentration of DA and its metabolites(DOPAC)were also measured in the 2 animal models in order to assess the level of DA involvement in each of the models(the less the change,the lower the involvement).Results(1)Similar myopic degree was induced in both the deprived and defocused eyes(-4.06 D vs.-3.64 D)at 11 days of the experiment.(2)DA and DOPAC levels were reduced in the deprived eyes but did not change significantly in the defocused eyes compared to the fellow and normal control eyes.(3)A subconjunctival injection of APO(from day 1 to 11)at concentrations from 2.5 ng to 250 ng/eye reduced axial myopia treated by form deprivation in a concentration-dependent manner. (4)By contrast,the effectiveness of APO treatment(at concentration from 2.5 ng up to 25 mg/eye)was significantly lower in inhibition of the defocus-induced myopia and the associated axial *** DA signaling may play a more critical role in form deprivation myopia than in defocus-induced myopia,raising a question whether the mechanisms of DA signaling are different under these two types of experimental myopia.

关键词： myopia dopamine guinea pigs form deprivation defocus

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P2X7 receptor-mediated microglia activation and glycine release from BV2 cell line

P2X7 receptor-mediated microglia activation and glycine rele...

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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： Wen-Juan HE,Jian CUI,Lu DU,Yan-Dong ZHAO,Huai-Zhen RUAN~* Department of Neurobiology,College of Basic Medical Sciences,Chongqing Key Laboratory of Neurobiology,Third Military Medical University Chongqing,400038,China

Objective Microglial activation is an integral part of neuroinflammation and neurodegenerative disorders, and extracellular ATP promotes the *** one important member of the family of ATP-sensitive ionotropic P2X receptor,P2X receptors play a role in microglia *** microglia can secrete many neurotransmitter and proinflammatory cytokines by the response to neuroexcitatory *** the present study,we explored the relationship of P2XR with microglia activation in neuropahtic pain,and examined the mechanisms of 3-O-（4-benzoyl） benzoyl ATP（BzATP）on glycine release from BV2 microglia cell *** The interaction between P2XR and microglia was identified by *** concentration of[Ca] in BV2 cell was examined by using confocal laser scanning microscopy and glycine release form BV2 cell was determined by ***（1） Immunohistochemical results have shown that dorsal horn spinal microglia was activated in neuropathic pain,and it can be inhibited by blocked P2X7R activation in L4-6 spinal cord using the selective P2XR antagonist BBG.（2） Immunofluorescence activity showed that P2X receptor protein was expressed in BV2 microglia *** induced [Ca] increase,which can be inhibited by BBG.（3）BzATP induced glycine release was mediated by P2X receptor, but there was no significant difference in glutamate and aspartate ***,release of glutamate by BzATP was abolished by Chelerythrine chloride but was unaffected by dihydrochloride *** P2X receptor induced microglia activation,and evoked glycine release under pathological condition,may modulate the activity of synapses in spinal cord.

关键词： P2X7 receptor microglia BzATP glycine

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Exogenous hydrogen sulfide improves rat cognitive deficits caused by brain ischemia

Exogenous hydrogen sulfide improves rat cognitive deficits c...

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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： Zhan-Yong LI~1,Zhuo YANG~2,Tao ZHANG~(1,*) 1 College of Life Science,Nankai University,Tianjin 300071,China 2 College of Medicine,Nankai University,Tianjin 300071,China

Objective Hydrogen sulfide（Hs） has been classified as a third novel gasotransmitter signaling molecule following nitric oxide and carbon *** evidence has shown that Hs produces physiological and pathophysiological functions in many organs and *** present study is designed to address the hypothesis that exogenous Hs could improve rat cognitive deficits induced by brain ischemia,and to explore the corresponding *** Rats were subjected to bilateral common carotid artery permanent occlusion for 15 days,and then spatial learning and memory was examined by Morris water maze（MWM） *** were administered with sodium hydrosulfide（NaHS,as an Hs donor,5.6 mg/kg/day） *** long-term potentiation （LTP） from Schaffer collaterals to CAl region was *** morphology of neurons in CAl region of hippocampus was determined by hematoxylin and eosin *** Hs content in hippocampus was *** addition,growth-associated protein-43（GAP-43） and Tumor necrosis factor-alpha（TNF-α） expression in CAl region of each rat was analyzed by immunohistochemical *** Exogenous Hs significantly improved spatial cognition deficits induced by brain *** test showed the escape latencies were prolonged significantly post brain ischemia（P<0.001）,whereas NaHS treatment could shorten the prolonged escape latencies（P<0.01）. Meanwhile,quadrant dwell time was increased after NaHS treatment（P<0.05）.The Hs level in hippocampus of the rats endured NaHS treatment post ischemia was higher than that of ischemia rats（P<0.001）.In vivo LTP data showed that exogenous Hs could enhance the synaptic plasticity in hippocampus neurons in ischemic *** Hs could inhibit the edema around pyramidal neurons and the nuclear shrink induced by ischemia,promote the expression of GAP-43 and TNF-αin the CAl region of hippocampus post *** Exogenous Hs has protective effects on neurons of hippocampus in brain

关键词： hydrogen sulfide spatial cognition synaptic plasticity brain ischemia

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AAV mediated BDNF expression combined with BDNF protein rescues rat retinal ganglion cells and visual function after acute elevation of intraocular pressure

AAV mediated BDNF expression combined with BDNF protein resc...

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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： Ruo-Tong REN,Zhi-Ping LIU,Shi-Gang HE~* State Key Laboratory of Brain and Cognitive Sciences,Institute of Biophysics,Chinese Academy of Sciences,15 Datun Road,Beijing 100101,China

Objective RGC loss is reported in many optic neuropathies,such as glaucoma,ischemia,et *** RGCs transmit the information processed by the retina to higher visual centers,loss of RGCs inevitably leads to impairment of visual *** is one of the most potent and most frequently used neurotrophic factors, widely applied in both protection and rescue of ***-associated virus(AAV) is by far most suitable viral vector for gene therapy because of sustained expression and *** this study,we asked whether AAV mediated BDNF expression is possible to rescue RGCs after acutely elevated intraocular pressure,furthermore,supplement the gene therapy with BDNF protein to compensate the slow onset of AAV mediated expression? If BDNF did rescue RGCs,then what is the mechanism? Methods Rat model was established with acute elevation of intraocular pressure,followed by intravitreal injection of BDNF-expressing AAV vectors and/or BDNF *** effect of RGCs and visual function was evaluated by quantification of surviving RGCs,visual evoked potential recording and visual behavior test based on two-alternative swimming *** Retinal ganglion cells(RGCs) underwent a continuous loss up to nine weeks after the intraocular pressure was elevated to 135 mmHg for 45 *** constructed an AAV vector to express BDNF to rescue *** mediated BDNF expression significantly rescued RGCs and visual *** BDNF protein to compensate the slow onset of exogenous gene expression achieved a much greater rescue *** administering BDNF without gene therapy,RGCs still underwent a significant reduction at the end of 9th *** further demonstrated that BDNF rescued RGCs through activating TrkB receptors through autocrine and paracrine mechanisms to improve axon *** improvements in visual function were apparent in increased amplitude and decreased latency of P1 component of visual evoked *** in behavioral tests,visual acui

关键词： glaucoma intraocular pressure(IOP) retinal ganglion cell(RGC) rescue brain-derived neurotrophin(BDNF) adeno-associated virus(AAV)

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Autophagic dysfunction in amyotrophic lateral sclerosis

Autophagic dysfunction in amyotrophic lateral sclerosis

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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-Jie ZHANG,Liang LI,Sheng CHEN,Wei-Dong LE 1 Neurogenomics,Institute of Health Sciences,SIBS,CAS-SJTUSM,Shanghai 200025,China 2 Neurology,Baylor College of Medicine,Houston,TX,USA

Aberrant protein misfolding may contribute to the pathogenesis of amyotrophic lateral sclerosis(ALS) but the detailed mechanisms are largely *** investigate if there is any autophagic alteration in ALS and used SOD1G93A mutant mice,a model of ALS to examined the processings of autophgy related molecules(LC3, Beclin-1,p-mTOR,p62,p-P70,p62,Atg5 and Atgl2 processing) by immunostaining and Western blot in the spinal cord and other central nervous *** have demonstrated that the autophagic protein marker LC3-Ⅱis markedly and specifically increased in the spinal cord motor neurons(MNs) of the ALS *** microscopy and immunochemistry studies have shown that autophagic vacuoles are significantly accumulated in the dystrophic axons of spinal cord MNs of the ALS *** these changes in the ALS mice appear at the age of 90 d when the ALS mice display modest clinical symptoms;and they become prominent at the age of 120 *** clinical symptoms are correlated with the progression of MNs ***,we have found that p62/SQSTM1 is accumulated progressively in the spinal cord,indicating that the possibility of impaired autophagic flux in the SOD1G93A ***,to our surprise,we have found that treatment with autophagy enhancer rapamycin accelerates the MNs degeneration,shortens the life span of the ALS mice,and has no obvious effects on the accumulation of SOD1 *** addition,we have demonstrated that rapamycin treatment in the ALS mice causes more severe mitochondrial impairment,higher Bax levels and greater caspase-3 *** findings suggest that selective degeneration of MNs is associated with the impairment of the autophagy pathway and that rapamycin treatment may exacerbate the pathological processing through apoptosis and other mechanisms in the ALS mice.

关键词： ALS motor neuron degeneration protein aggregation autophagy apoptosis

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Dynamic collaboration of Navl.6 and Nav1.2 in action potential initiation

Dynamic collaboration of Navl.6 and Nav1.2 in action potenti...

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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： Han HOU~(1,**),Wen-Qin HU~(1,**),Yuan ZHAO(~2,3),Xiu-Feng YANG~1,You-Sheng SHU~(1,*) 1 Institute of Neuroscience,State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China 2 Britton Chance Center for Biomedical Photonics,Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology,Wuhan 430074,China 3Key Laboratory of Biomedical Photonics of Ministry of Education,Huazhong University of Science and Technology, Wuhan 430074,China

It has been shown recently that in pyramidal neurons of the rat prefrontal cortex,low-threshold Na1.6 and high-threshold Na1.2 channels preferentially distribute at the distal and proximal axon initial segment（AIS）, responsible for action potential initiation and backpropagation,***,this scenario is confined to situations where action potentials initiate from the resting membrane potential（V）,given that in physiological conditions,somatic V of pyramidal cells always fluctuate under synaptic *** we report that depolarization of somatic V,during either current injection or "Up" states in slow oscillation,substantially inactivates AIS sodium channels（NaChs）and,strikingly,reduces the availability of inactivation-prone Na1.6 in distal AIS to a level lower than 10%.Further modeling study captures this observation,and suggests that a-30 times higher density of AIS NaChs compared with the soma and a 4 mV shift in voltage dependence of Na1.6 and Nal.2 found previously might be set so in order to guarantee a stable action potential initiation site within a physiological range of somatic V,especially during severe inactivation of ***,our findings might resolve the discrepancy between different previous studies on axonal NaChs,by arguing that the dynamic collaboration of NaChs should be taken into account when comparing the anatomical and the functional results.

关键词： axon initial segment action potential initiation Nav1.2 Nav1.6 inactivation

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Cytokines induce the expression and activity of cathepsin C in microglia in LPS-induced neuroinflammation

Cytokines induce the expression and activity of cathepsin C ...

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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： Kai FAN~1,Bin FAN~2,Jian-Mei MA~(1,*) 1 Anatomy department of Dalian Medical University,Dalian 116044,China 2 Graduate school of Dalian Medical University,Dalian 116044,China

Objective Neurodegenerative diseases accompany neuroinflammatory pathological process,during which injury or loss of neurons often *** a result,cognition,learning or movement function is severely *** far,the mechanism concerned is *** C（also called dipeptidyl peptidase,DPPI）,a lysosomal cysteine protease,activates granule-associated serine proteases which play important roles in host reponses to bacterial infection in periphery ***,whether cathepsin C participates in regulation of the process of inflammation in CNS remains *** present study is to explore the role of cathepsin C in CNS inflammatory *** An acute inflammation mice model was established by LPS（25 mg/kg,b.w.） intraperitoneally single *** different time points after LPS injection,the cellular localization,expression pattern and level of cathepsin C was detected by immunohistochemistry and Western *** expression of Cathepsin C mRNA, IL-1βmRNA and TNFa mRNA were studied by in situ hybridization and *** vitro,BV mouse microglia lines were treated with various concentrations of LPS or IL-1B for 6 *** the expression of cathepsin C mRNA and the secretion of cathepsin C were detected by RT-PCR and ELISA,*** activity of cathepsin C was measured by chromogenic substrate *** After LPS injection,the expression of cathepsin C and cytokines in the brain was *** 24 h point,the activated microglia started to express cathepsin C and its expression maintained at the highest *** contrast,cathepsin C was exclusively expressed in neurons at 6 h point after LPS *** vitro,both cathepsin C mRNA expression and cathepsin C protein secretion were increased in LPS or IL-1β-treated BV cells in a dose-dependent *** addition,the activity of cathepsin C was also enhanced after *** The results indicate that cytokines induce the expression and activity of cathepsin C in microglia i

关键词： cathepsin C neuroinflammation cytokine microglia

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Reversal learning in radial-arm maze training possibly interferes with latent inhibition of adult rats

Reversal learning in radial-arm maze training possibly inter...

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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： Qiang GU,Bang-An WANG,Meng-Ya WANG~* Cell electrophysiology Laboratory,Wannan Medical College,Wuhu 241002,China

Objective Latent inhibition(LI) denotes that a prestimulus with repeated presentation but without reinforcement(***-expose) will interfere with the subsequent learning task related with this stimulation and its change is one important manifestation of *** work aims to explore whether behavioral training of reversal learning could interfere with LI of adult *** Twenty adult male Sprague-Dawley rats(body weights;100 - 120 g each) were randomly divided into two groups,pre-expose group(PE) and non pre-expose group (NPE).The experimental protocol includes 3 stages:First,Gemini avoid system was used to observe LI phenomenon of rats,in which the number of active avoidance,no response,and avoiding latency were detected by the *** LI test procedvire contained adaptation phase,pre-expose phase,and conditioning ***,the followed intervention training of reversal learning was conducted in the Habitest radial-arm maze system(8 arms).The process included adaptation phase,acquisition phase,and reversal learning phase,in which correct percent of running into arms of rats were ***,after the training of reversal learning,LI was tested in the same approach once *** (1) In the first LI test,the difference of no response number,and the avoiding latency was statistically significant(two-sample t test,P<0.05) between the PE and NPE groups,while the difference in the number of active avoidance was not significant(P>0.05).These results mean that PE group shows latent inhibition.(2) In the intervention training of radial-arm maze,the difference in correct percentage of running into arms in two groups at the final day of acquisition phase(A8 day) and the first day of reversal learning phase(Rl day) was significant,respectively(paired Mest,P<0.001),indicating the occurrence of the reversal learning.(3) In the second LI test,the number of active avoidances or no responses,and avoiding latency did not differ between rats in the PE a

关键词： latent inhibition reversal learning schizophrenia

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The characteristics of the transmission of enhanced susceptibility after acquired febrile seizure in rats

The characteristics of the transmission of enhanced suscepti...

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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： Bo FENG,Yun-Jian DAI,Deng-Chang WU,Shi-Hong ZHANG,Zhong CHEN~* Department of Pharmacology Key Laboratory of Medical Neurobiology of Ministry of Health of China Zhejiang Province Key Laboratory of Neurobiology College of Pharmaceutical Sciences,Zhejiang University, Hangzhou 310058,China

Objective Early exposure to enriched environment may deeply influence the developing synaptic plasticity and this effect can transmit to *** febrile seizures(FSs) are associated with a risk of subsequent temporal lobe *** this study,we tested whether this acquired enhancement of susceptibility can be transmitted to offspring,and what is the risk factor during this *** Prolonged seizures were evoked by exposing rat pup(9) to a hyperthermic environment of(44±2)℃.Kainic acid,pentylenetetrazol(PTZ) and maximal electroshock(MES) were used to test the seizure susceptibility in rats that experienced FSs(FO) and the susceptibility of seizures in the following 2 generations(Fl,F2) was tested as *** mothers were mated with non-FSs fathers and vice versa to reveal which parent contributed to the transmissional ***(ⅰ) Both MES and kainic acid induced higher scores of seizures in the Fl-FSs rats,while there is no significant difference in PTZ induced seizures compared with those of control rats,(ⅱ) There was no significant difference in scores of MES-induced epilepsy between the F2 control and FSs groups,(ⅲ) Offspring of FO rats that had experienced 10 FSs displayed higher scores to MES-induced seizures than that of offspring in control group and 4*2 FSs group;however, offspring of FO rats that had experienced 4*2 FSs did not display significant difference to MES-induced seizures, (iv) Scores of MES-induced seizures in Fl rats mated by FSs mother and non-FSs father are higher than that by FSs father and non-FSs *** These results indicate that(1) the transgenerational transmission showed severity-dependent and model-dependent characteristics;and(2) the transgenerational transmission was limited to Fl generation through the *** finding may suggest non-Mendelian transgenerational inheritance play a role in the epileptogenesis.

关键词： febrile seizures kainic acid pentylenetetrazol maximal electroshock transmission

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