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The effects of diphenidol on brain cognitive processing in special environment and space flight

The effects of diphenidol on brain cognitive processing in s...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Lin-Jie Wang Siyang He Dongbin Niu Desheng Wang Qi Zhao Cheng Tan Peng Zou Jianping Guo Yuhua Yao Jianli Zhang Yunlong Xu Jian Jiang Ming Wei State Key Laboratory of Space Medicine Fundamentals and Application China Astronaut Research and Training Center

Intramuscular injection of promethazine was recommended as a routine therapy for space motion sickness in NASA. In China oral diphenidol is more often used. As diphenidol has mild anticholinergic effects, it is supposed that diphenidol may have some negative role in brain cognitive processing. Series studies have been performed to explore the role of diphenidol on brain cognitive processing. They are comparative study of the effects of diphenidol, promethazine, dimenhydrinate and placebo on auditory cognitive processing, the effects of acute-6? head-down tilt on space and feature attention immediately after diphenidol administration for 5 times, the effects of 30 days-6? head-down bed rest on space and feature attention and the effects of space flight on space and feature attention after preventive medication of oral diphenidol administration for 3 days. It was found that compare with promethazine and dimenhydrinate, the administration of diphenidol had little effects on auditory cognitive processing. It was found that the reaction time shortened for about 20 to 30 ms when performing choice attention task in head-down or head-up than in supine. P3 amplitudes were decreased when performing no response task under head-down or head-up tilt after diphenidol administration. P3 amplitudes were decreased when performing color selective attention task and increased when performing direction selective choice task after diphenidol administration compared with placebo. The P3 amplitudes increased in the coaction of diphenidol and blood distribution compared with in supine after diphenidol administration. The mean amplitudes of P1 and N1 for target ERPs decreased in the 3rd day during bed rest. In color/direction selective response task, the P1 latencies for target ERPs on the 3rd and 30 th day during bed rest were longer than on the 15 th day during bed rest. The perception of feature attention signal, the differentiation and judgment in space attention slowed down in the 8th

关键词： diphenidol brain cognitive processing event-related potentials head-down bed rest space flight

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Exercise enhances stress coping despite increasing corticosterone,likely by upregulating the dopamine level in the medial prefrontal cortex

Exercise enhances stress coping despite increasing corticost...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： C Chen S Nakagawa Y Kitaichi Y An Y Omiya N Song M Koga T Inoue I Kusumi Department of Psychiatry Hokkaido University Graduate School of Medicine

Introduction: Although exercise has been shown to improve stress coping, the underlying neurotransmitter mechanism remains largely unknown. Further, exercise activates the HPA axis and increases glucocorticoid(CORT), the ‘stress hormone', which impairs stress coping. Thus exercise should, through some mechanism, override the detrimental effects of elevated CORT. The purpose of the present study is to investigate by what neurotransmitter(s) exercise overrides the detrimental effect of elevated CORT within the medial prefrontal cortex(m PFC), the brain center of stress coping. Methods: Exercise rats were raised with three weeks of free access to wheels while control rats were raised in same cages but without wheels. The forced swim test was performed at 19:00, the time at which lights off and around which(circadian) CORT peaks. A separate group of rats were raised the same, and m PFC microdialysis sampling was performed before and after the forced swim test. We used the high-performance liquid chromatography system to detect neurotransmitters, and an ELISA kit to measure CORT. Results and discussion: Three weeks of voluntary wheel running reduced immobility time in the forced swim test, suggesting stress coping effect. Basal level of extracellular CORT(17:00-19:00, around circadian peak) in the m PFC was higher in exercise than control rats. When subjected to forced swim, both exercise and control rats showed increased CORT. However, CORT in exercise rats decreased to basal level earlier than control rats. Extracellular dopamine level in the m PFC was increased in exercise rats, both at the basal level and after forced swim. Basal level of extracellular glutamate level in the m PFC tended to be reduced in exercise rats. There was no group difference with regard to serotonin, noradrenaline, glutamine, glycine, taurine, or alanine. These results suggest that elevated dopamine level in the mPFC may be a mechanism by which exercise improves stress coping, and overrides th

关键词： Exercise Corticosterone Dopamine Medial prefrontal cortex,Immobility Stress

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The influences of period1b gene deficiency on the visual function of zebrafish

The influences of period1b gene deficiency on the visual fun...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Ke Nie Kun Wang Han Wang Bing Hu Chinese Academy of Sciences Key Laboratory of Brain Function and Disease School of Life SciencesUniversity of Science and Technology of China Center for Circadian Clocks Soochow University School of Biology & Basic Medical Sciences Medical CollegeSoochow University

Objective The circadian clock is a biological mechanism that displays an endogenous, entrainable oscillation of about 24 hours, of which the molecular basis is the transcription/translation feedback system consists of several clock genes. The visual system of zebrafish is regulated by the circadian clock. Period1b(Per1b) is a special circadian gene of zebrafish, which plays an important role in the transcription/translation feedback system. This study focuses on the influences on zebrafish visual system caused by the lack of per1 b. Methods We setup two apparatus for measuring larval zebrafish optokinetic response(OKR) and adult zebrafish escape response. Results Per1b-/- larvae exhibited decreased behavioral contrast sensitivity, meanwhile there was a significant reduction in the number of dopaminergic interplexiform cells(DA-IPC) in the retinae of per1b-/- larvae, and the retinal dopamine level decreased either. Dopamine applied in vitro can restore the contrast sensitivity of per1b-/- larvae effectively. Color vision tests proved that per1b-/- larvae showed a significant short-wave light visual defect, which could not recovered by dopamine administration. Visual acuity tests showed that visual acuity of per1b-/- larvae declined in the full spectrum of white light and short-wave light, but the optimal spatial frequency remained at 0.044 cpd. In addition, the circadian rhythm of the contrast sensitivity of per1b-/- larvae presented a phase shift, which could not be restored by dopamine. The 6-OHDA led to decreased behavioral contrast sensitivity in AB/WT larvae by partially damaging DA-IPCs. Adult fish visual sensitivity tests showed that visual sensitivity of per1b-/- adult fish maintains normal circadian rhythm. However, its threshold was always higher. Conclusion per1 b gene deficiency caused a series of visual defects in zebrafish, which may be relevant to the reduced of the number of dopaminergic neurons(interplexiform cells) in the retinae, abnormal distribut

关键词： per1b gene Optokinetic response(OKR) contrast sensitivity DA-IPC visual sensitivity visual acuity color vision dopamine

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Autism-like behaviors and germline transmission of transgenic monkeys overexpressing MeCP2

Autism-like behaviors and germline transmission of transgeni...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Xiao Li Jun-Tao Zhang Tian-Lin Cheng Cheng Cheng Xiang Yu Neng Gong Wen-Hao Zhou Zilong Qiu Institute of Neuroscience Key Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain ScienceShanghai Institutes for Biological SciencesChinese Academy of Sciences Department of Neonatology Children's Hospital of Fudan University

Methyl-Cp G binding protein 2（Me CP2） plays critical roles in transcriptional regulation and microR NA processing. Mutations in MECP2 gene are found in 90% of patients with Rett syndrome, a severe form of developmental disorders with autistic phenotypes. Duplications of MECP2–containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders（ASD）. Although the Mecp2-null mice recapitulate most developmental and behavioral defects found in Rett syndrome patients, it has been difficult to identify autism-like behaviors in the mouse model with MeC P2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkey（Macaca fascicularis） expressing human Me CP2 in the brain exhibited autism-like behaviors and showed germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by Western blotting and immunostaining of brain tissues of transgenic monkeys and chromosomal distributions of the transgenes were characterized by deep sequencing. As compared to wild-type（WT） monkeys, MECP2 transgenic（TG） monkeys exhibited higher frequency of repetitive circular locomotion and elevated human gaze-induced stress responses, as measured by the threat-related anxiety and defensive test for monkeys. The TG monkeys also showed less time spent with othermonkeys within the same group（reared together for ~ 6 months） and reduced interaction time when paired with another monkey in the same cage. The cognitive functions of TG monkeys were largely normal in Wisconsin General Test Apparatus, although some showed signs of stereotypic cognitive behaviors. Notably, we succeeded in generating 5 F1 offspring of MECP2 TG monkeys by intracytoplasmic sperm injection with sperms obtained from one male TG monkey, showing germline transmission and Mendelian segregation of the MECP2 transgene in the F1 progeny. Together, these results indicate the feasibility and reliability of using the lentivirus-based met

关键词： Autism-like behaviors and germline transmission of transgenic monkeys overexpressing MeCP2

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Dose-dependent effects of 6-hydroxydopamine on refractive development and form-deprivation myopia in C57BL/6 mice

Dose-dependent effects of 6-hydroxydopamine on refractive de...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Xiao-Hua WU Kang-Wei QIAN Yun-Yun LI Guo-Zhong XU Shi-Jun WENG Xiong-Li YANG Yong-Mei ZHONG Institute of Neurobiology Institutes of Brain ScienceState Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain ScienceFudan University

Objective We recently reported that retinal dopamine(DA) levels are unaltered during the development of form-deprivation myopia(FDM) in the C57BL/6 mouse, which challenges the traditional view that reduced retinal DA levels mediate the development of myopia. To further explore the role of retinal DA in mouse eye growth, we investigated the effects of retinal dopaminergic system lesion by 6-hydroxydopamine(6-OHDA) on refractive development and FDM formation in this mouse strain. Methods 6-OHDA of three different doses(6.25 μg, 12.5 μg and 50 μg) were intravitreally applied to the right eye using a micro-injector, and the left eye served as control. Retinal DA levels were assessed by HPLC analysis. Refractions were measured by an automated eccentric infrared photorefractor in animals raised in normal visual environment, and in those wearing an occluder on the injected eye for four weeks to induce FDM. To evaluate the overall effects of 6-OHDA, retinal functions were analyzed by electroretinographic(ERG) recordings, and dopaminergic amacrine cells labeled immunohistochemically were counted. Results While at all three dosages 6-OHDA markedly reduced retinal DA levels for at least 31 days, the injection of 6-OHDA of 6.25 μg and 12.5 μg neither significantly attenuated ERG a- and bwave amplitudes, nor did it affect the number of TH+ cells, suggesting that it did not induce toxic, non-specific effect on physiological functions of the retina. These two doses were therefore used in the experiments to be described. With normal visual experience, the 6-OHDA-injected eyes became markedly myopic relative to their fellow eyes, and the degree of myopic shifts was dose-dependent(approximately-2.8 D for 6.25 μg and approximately- 4.6 D for 12.5 μg 6-OHDA treatment), suggesting that an intact retinal dopaminergic system providing complete DA stores is essential for normal refractive development in the C57BL/6 mouse. Furthermore, form-deprivation failed to induce further myopic shifts

关键词： form-deprivation myopia dopamine 6-hydroxydopamine electroretinography retina

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Hydrogen sulfide exerts depressive cardiovascular effects on Urotensin Ⅱ induced hypertension in SD rats

Hydrogen sulfide exerts depressive cardiovascular effects on...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Hai-Yan Xu Na-Na Zhang Xiao-Ni Liu Chun-Mei Xia Ying Huang Rui Wang Ning Lu Department of Physiology and Pathophysiology Fudan University

Objective: Explore the central cardiovascular effects of H2 S on Urotensin II(UII)-induced hypertension. Methods: Double immunofluorescent staining and confocal microscope was used to explore the expression and distribution of CBS in the neurons of RVLM. In order to observe the central cardiovascular effects of H2 S on UII-induced hypertension, intracerebroventricular(ICV) infusion and microinjection in rotral ventrolateral medulla(RVLM) were employed in SD rats. To explore the role of reactive oxygen species(ROS) in the central cardiovascular effects of H2 S, the ROS level and NADPH oxidase activities of RVLM area were detected by DHE fluorescence method(qualitatively) and lucigenin flurescene method(quantitatively). Results:(1) We found that CBS expressed in the RVLM neurons.(2) The infusion of ICV showed that UII( 20 nmol/10μL) significantly increased mean arterial pressure(MAP)(P<0.05);pretreatment with Na HS( 4 nmol/10μL), could significantly inhibit the effect of UII on MAP(P<0.05).(3) Microinjection UII( 2 nmol/0.1μL;5nmol/0.1μL) into RVLM could significantly increase MAP in SD rats(P<0.05);pretreatment with Na HS( 0.4 nmol/0.1μL) could significantly inhibit the increase of MAP induced by UII(P<0.05).(4) Microinjection of SAM(a CBS activator) into RVLM inhibited the increase of MAP induced by UII, while HA(a CBS inhibitor) could not.(5) The a CSF + UII group presented significantly higher ROS production in comparison with a CSF group(P<0.05) and Na HS + UII group could significantly reverse the increase of superoxide anion production induced by UII(P<0.05).(6) The aC SF + UII group showed significantly higher NADPH oxidase activity than that of a CSF group(P<0.05) and H2 S can reverse the activation of NADPH oxidase(P<0.05), which suggesting that NADPH oxidase might mediate the cardiovascular effects of H2S. Conclusion: In summary, our results suggested that H2S could reverse the UII-induced hypertensive effects of in SD rats. We supposed that H2S could inhib

关键词： UrotensinⅡ ROS H2S NADPH oxidase SOD RVLM

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Lycium barbarum polysaccharides delays the onset of exposure to PFOS elicited infertility and spatial memory deficits in rat

Lycium barbarum polysaccharides delays the onset of exposure...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Tianqi Wang Jianying Tian Jing Cui Sengseng Yang Weicai Yang Basic Medical School Ningxia Medical University

Lycium barbarum polysaccharide(LBP) is a traditional Chinese wolfberry major functional components. Recent there is emerging evidence show that it has neuro-protection and reproductive protection. This study is aimed to investigate the effect of PFOS on the reproductive and working memory, as well as the early intervention of LBP. Sparague-Dawley rats, male and female in 10 d, were randomly divided into control group, PFOS group, PFOS+LBP group, LBP group with 15 rats per group. Spatial memory deficits were established by injection of PFOS subcutaneously for 28 ds. For LBP or PFOS+LBP group was administered simultaneously. Control group rats were injected with normal saline. All groups were treated for 4 weeks. Then the weights and the reproduction and offspring were observed. The learning and spatial memory abilities were detected by Morriswater maze test. The Results show that PFOS group rats were inactivity, low appetite, and slow growth retardation with the extension of PFOS exposure dependently, Compared with the control group. The female rats in PFOS group were infertility after PFOS exposure. There were offspring in PFOS+LBP group, but the high death, low survival rates and low-weights after born were significantly than that of the control group(p<0.05). The death rates and growth weights in LBP group were little lower and high than the control group(p≥0.05). The escape latencies in PFOS group from week 6 were longer and the swimming time in the platform quadrants were significant shortened than in controls with PFOS exposure time dependently(6ws, p<0.05, 9ws, p<0.01). Compared with PFOS group, the escape latencies and times in the platform quadrant of PFOS+LBP group from week 6 were shortened and increased significantly(p<0.05, p<0.05). Thus, PFOS with chronic exposure can directly induced the reproductive toxicity on rats and Lycium barbarum polysaccharides may be a potential inhibition for methyl mercury chloride induced reproductive toxicity and spatial m

关键词： Lycium barbarum polysaccharide,spatial memory,reproductive toxicity,protective effect

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Specific change and regulation of serum proteins in Parkinson's disease patients

Specific change and regulation of serum proteins in Parkinso...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Xiaoliang Wang Yingni Sun Ling Wang Wenwen Lu Biao Chen Department of pharmacology Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical Sciences Xuanwu Hospital Capital Medical University

Recently we demonstrated that the protein ITI-H4(inter-alpha-trypsin heavy inhibitor) and Apo-A-IV were specific changed in the serum of Parkinson disease patients(Lu et al, Plos One, 2014). It was interesting that each protein was found existing two subunits in serum. The full size(120 k Da) ITI-H4 was increased and the fragmented ITI-H4(35 k Da) was decreased in PD patients. Meanwhile, the subunit A of Apo-A-IV(46 k Da) was not changed in PD group, but the subunit B(26 k Da) was significantly decreased. Above data was obtained from 20 PD patients and 20 health people. In order to further demonstrate and validate the results, we observed the change of both proteins in 180 PD patients and investigated the regulation of the two proteins in the present study. The blood samples were collected from PD patients aged 50 – 75 and they were diagnosed PD in 5 years. The control blood samples were collected from the health people with the same age range. The serum proteins of ITI H4 and Apo-A-IV were semi-quantity determined by using western blot method. It was showed that the expressions of full-long ITI H4(120 k Da) increased 29%and the 35 k Da fragment was decreased 18% in PD group compared with control group. The ratio of 120 k Da/35 k Da was enhanced 68% in PD patients compared to control. The expression of subunit A(46 k Da) of Apo-A-IV was no difference between PD and control groups. However, the 26 k Da subunit(subunit B) was decreased by 48% in PD patients. Our results are accordant with our previous finding. The regulatory mechanisms of both proteins were also investigated in this study. Two enzymes for metabolism of ITI H4 and Apo-A-IV were demonstrated altered in serum or plasma of PD patients. The proteins and the subunits might be used as blood biomarkers of PD. They are also important in studies of pathogenesis and the new drug development for PD.

关键词： Parkinson's disease blood,biomarker,ITI H4 Apo-A-IV

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Classification of excitatory and inhibitory neurons in the six layers of somatosensory cortex of rat

Classification of excitatory and inhibitory neurons in the s...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yun Wang Qi-Qin Li Henry Markram BBP team School of Optometry & Ophthalmology Wenzhou Medical University Brain Mind Institute Ecole Polytechnique Fédérale de Lausanne (EPFL)

For nearly two decades, we recorded 14,045 and labeled 2,052 and reconstructed 1005 neurons constituting the microcircuit in all six neocortical layers of somatasensory cortex(SSC) of P14-P16 rats using multi-neuron patch-clamp electrodes in in vitro slices. In the 2,052 cases, the anatomical staining of the axonal and dendritic arbors of neurons was sufficiently complete to allow classification into different morphological types(m-types) according to morphological and naming criteria established over the last century. We digitally reconstructed the 3D morphology of 1005 of these neurons, creating a sample of reconstructed neurons for the different m-types in each cortical layer. This process yielded 55 distinct m-types(13 excitatory and 42 inhibitory) for building up the SSC simulating column in the HBP. The excitatory neurons in the six cortical layers were classified mainly according to morphological features of apical dendrites. From layer 1 to layer 6, excitatory pyramidal cells(PCs) became more diversified in their morphologies, from barely a few excitatory cells in layer 1 up to six types in layer 6. All PC types showed laminar specificity in six cortical layers. Inhibitory interneurons in the six layers were classified mainly according to morphological features of axons. In contrast to excitatory cells, inhibitory interneurons presented the same compositions of nine types throughout all individual layers except of layer 1 in which six interneuron types were specific and distinguishable each other. The nine types of interneurons distributed in each lamina from layer 2/3 to layer 6 were large basket cell(LBCs), nest basket cell(NBC), small basket cell(SBC), Martinotti cell(MC), double banquet cell(DBC), bipolar cell(BP), chandelier cell(Ch C), bitufted cell(BTC), neurogliaform cell(NGC). However, some interneuron types, especially those with translaminar axonal clusters, presented laminar specificity to a certain extent in terms of their local axonal projectio

关键词： somatasensory cortex morphological types excitatory pyramidal cells Inhibitory interneurons apical dendrites axons

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Hypothalamic modulation on the medial vestibular nucleus and its motor control

Hypothalamic modulation on the medial vestibular nucleus and...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jing-Ning ZHU Jian-Jun WANG State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology School of Life SciencesNanjing University

Central histaminergic and orexinergic systems both originate in the hypothalamus restrictedly but innervate almost the whole brain, including various subcortical motor structures. In brainstem, the medial vestibular nucleus(MVN), a key motor center for stabilization, coordination and compensation of head and eye movements, receives direct hypothalamic histaminergic and orexinergic projections. Here, we report that both histamine and orexin postsynaptically excite type-A and type-B neurons in the MVN in a concentration dependent manner. Na+-Ca2+ exchangers(NCXs) coupled to histamine H1 receptors and hyperpolarization-activated cyclic nucleotide-gated(HCN) channels linked to histamine H2 receptors co-mediate the strong postsynaptic excitatory effect of histamine on the MVN neurons. On the other hand, orexin 1 receptors(OX1Rs) and orexin 2 receptors(OX2Rs), together with their downstream coupling NCXs and nonselective cation channels(NSCCs), underlie the excitation of orexin on the MVN neurons. Furthermore, orexin increased the sensitivity of MVN neurons to the rectangle and ramp current stimulations without altering neuronal dynamic properties. And orexin also caused a frequency-dependent gain enhancement and phase-lead shift of MVN neurons to sinusoid-like current stimulations. Interestingly, endogenous orexinergic modulation on MVN neurons was critical when animals traversing a rotating balance beam as opposed to a static one. All these results demonstrate that histamine and orexin modulates not only excitability but also sensitivity of the MVN neurons and suggest that hypothalamic histaminergic and orexinergic innervation on MVN may play a crucial role in somatic motor control. The findings also suggest novel potential targets for clinical treatment of vestibular disorders, such as vertigo, motion sickness, nausea and nystagmus.

关键词： hypothalamus histamine orexin MVN vestibular reflexes motor control

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