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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届会员代表大会

作者： Zhi-Na ZHI Xiang-Tian ZHOU Jia QU Dong FENG Miao-Zhen PAN Ruo-Zhong XIE Run-Xia LU Fan-Jun SHI Xin-Jie MAO Jiang-Fan CHEN Mark D.P.WILLCOX School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical College 270 Xueyuan Road Wenzhou Zhejiang 325003 China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science Ministry of Health China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry.270 Xueyuan Road Wenzhou Zhejiang 325003 China School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical College 270 Xueyuan Road Wenzhou Zhejiang 325003 China School of Optometry and Vision Science The University of New South Wales Sydney NSW Australia School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical College 270 Xueyuan Road Wenzhou Zhejiang 325003 China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science Ministry of Health China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry.270 Xueyuan Road Wenzhou Zhejiang 325003 China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science Ministry of Health China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry.270 Xueyuan Road Wenzhou Zhejiang 325003 China Department of Neurology Boston University School of Medicine Boston MA 02118USA School of Optometry and Vision Science The University of New South Wales Sydney NSW Australia

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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Extensive brain structural network abnormality in first-episode treatment-na(i)ve 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届会员代表大会

作者： Zhuangfei CHEN Yingcheng WANG Siew E Chua Charlton Cheung Gráinne M.McAlonan Pak C Sham David A Collier Marco Picchioni Stefania Benetti Andrea Mechelli Nicolas Crossley Wei DENG Joseph P.Kambeitz Paul Allen Philip McGuire Tao LI Qiyong GONG Chaohua HUANG Lijun JIANG Mingli LI Zongling HE Qiang WANG Xiaohong MA St Andrew''s Academic Centre Institute of Psychiatry King''s College London NN1 5BG Division of Psychological Medicine and Psychiatry Section of Neuroimaging Institute of Psychiatry King''s College London London SE5 8AF UK Division of Psychological Medicine and Psychiatry Section of Neuroimaging Institute of Psychiatry King''s College London London SE5 8AF UK The Mental Health Center & Psychiatric laboratory West China Hospital Sichuan University Chengdu China The State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China Department of Psychiatry The University of Hong Kong Pokfulam S.A.R.China MRC SGDP Centre Institute of Psychiatry King''s College London London SE5 8AF UK Division of Psychological Medicine and Psychiatry Section of Neuroimaging Institute of Psychiatry King''s College London London SE5 8AF UK Department of Psychosis Study Institute of Psychiatry King''s College London London SE5 8AF UK Huaxi MR Research Center Department of Radiology West China Hospital Sichuan University Chengdu China

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.

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Rheb1 is required for mTORC1 and myelination in postnatal brain development

Rheb1 is required for mTORC1 and myelination in postnatal br...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Jia ZOU Ling-Xue GAN Mao-Wen LUO Qiao-Na YANG Yi-Yuan CUI Wan-Chun YANG Xiao-Qiang XIA Mi-Na CHEN Xia ZHAO Ying SHEN Po Yu CHEN Liang ZHOU Paul F.WORLEY Bo XIAO Xiao-Xia DU Yi-Fei JI Jia XU Jun-Long TIAN Wan-Xiang JIANG Yi ZOU Shou-Yang YU Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 USA The State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China Department of Neuroscience Zhejiang University Hangzhou 310058 China Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 USA The State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China Department of Neuroscience Zhejiang University Hangzhou 310058 China The State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China

mTor kinase is involved in cell growth, proliferation, and *** roles of mTor activators, Rheb1 and Rheb2, have not been established in *** generated mice with conditional genetic deletions of Rheb1 and *** deletion of Rheb1 (Actin-cre) results in embryonic death between E10.5 and E11.5 while mutant mice with germiline deletion of Rheb2 mature to adulthood without obvious physical *** cultured mouse embryonic fibroblasts (MEFs) from individual E10.5 embryos, insulin and amino acids activated mTORC1 signalings are selectively impaired in Rheb1-/-*** examine the roles of Rheb1 in vivo, we generated Rheb1 f/f, Nestincre mice in which Rheb1 was conditionally excised in neural progenitor *** mutants were born at expected Medelian ratios and survived up to 6 weeks after birth, mTORC1 signaling is abolished and mTORC2 signaling is increased in developing brain of Rheb1f/f, ***, in Rheb1 f/f, Nestin-cre mutants, the gross morphology of the brains at early postnatal stages was preserved, whereas the myelin formation in later developmental stages was significantly *** TSC mutants in which mTORC 1 signaling were upregulated were previously reported with hypomyelination phenotype, we generated Rosa26 Rheb1 transgenic mouse which conditionally express Rheb 1 in neural progenitor cells to examine whether increasing Rheb1/mTORC 1 activity promotes myelination, or causes ***1 transgene increases mTORC1 activity and promotes myelin formation in the brain, In addition, the Rheb1 transgene rescues mTORC 1 signaling and hypomyelination in the Rheblf/f, Nesin-cre *** study demonstrates that Rheb1, but not Rheb2, is critical for embryonic survival and mTORC1 *** Rheb1 is essential for myelin development in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability.

关键词： Rheb1 Rheb2 mTor myelination

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Identification of the role of phosphodiesterase in mediating memory:implication in Alzheimer's disease

Identification of the role of phosphodiesterase in mediating...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Han-Ting ZHANG Steven P.WILSON James M.O'DONNELL Yun-Feng LI Ying HUANG Yu-Fang CHENG Chuang WANG Qiang WU Rolf HANSEN Jiang-Ping XU Marco CONTI Beijing Institute of Pharmacology and Toxicology Beijing 100850 China Department of Pharmacology School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 China Division of Reproductive Biology Department of Obstetrics & Gynecology University of California San Francisco CA 94143 USA Department of Pharmacology School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 China Department of Pharmacology Physiology and Neuroscience University of South Carolina School of Medicine Columbia SC 29208 USA Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology West Virginia University Health Sciences Center Morgantown WV26506 USA Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology West Virginia University Health Sciences Center Morgantown WV26506 USA Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology West Virginia University Health Sciences Center Morgantown WV26506 USA

Objective Phosphodiseterase (PDE) is a superfamily of enzymes that catalyzes the hydrolysis of intracellular cAMP and/or *** the 11 PDE families (PDE1-11), PDE4 is the most important family in the control of intracellular cAMP *** has been well established that PDE4 plays an essential role in the mediation of ***, it is not known whether PDE4 is involved in memory associated with Alzheimer's disease (AD).The objective of this study was to identify the role of PDE4 and its isoforms (PDE4A-D) in AD-related *** Mice deficient in PDE4A, PDE4B, or PDE4D were microinfused with β-amyloid peptide 1-42 (Aβ42; 0.4 μg/side) or vehicle into bilateral dorsal hippocampi before memory tests using the object recognition, passive avoidance, and Morris water-maze *** silencing was used to identify the role of PDE4 variants in *** ofphosphorylated CREB (pCREB) in the hippocampus was also examined using Western blotting *** Mice deficient in PDE4A or PDE4D, but not PDE4B, displayed memory enhancement in one or all of the memory ***4A or PDE4D knockout mice also exhibited reversal of Aβ42-induced memory impairment, which was observed in wild-type mice in the object recognition, passive avoidance, and water-maze ***, microinfusions of lentiviral vectors containing microRNAs (miRNAs) that target long-form PDE4D splice variants mimicked the ability of PDE4D deficiency to enhance memory in normal mice; the miRNAs also reversed Aβ42-induced memory deficits in the radial arm maze test in ***, Aβ42 decreased pCREB levels in the hippocampus of wild-type mice or negative control sequence-treated rats, but not mice deficient in PDE4A or PDE4D nor rats treated with *** These results suggest that both PDE4A and PDE4D, in particular the long-form PDE4D isoforms, play an important role in the mediation of memory associated with Alzheimer's *** PDE4A or PDE4D may b

关键词： phosphodiesterase memory Alzheimer' s disease gene knockout gene knockdown PDE4 subtypes CREB miRNAs

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Proteolipid protein 1 gene mutations in 33 Chinese patients with pelizaeus-merzbacher disease and prenatal diagnosis of 5 fetuses in 3 Chinsese families with PMD probands

Proteolipid protein 1 gene mutations in 33 Chinese patients ...

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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： Jing-Min WANG~1,Ye WU~1,Hai-Juan ZHAO~(1,2),Jing SHANG~(1,2),Yan-Ling YANG~1,Jiong QIN~1,Xi-Ru WU~1, Yu-Wu JIANG~(1,*) 1 Department of Pediatrics,Peking University First Hospital,Beijing 100034,China 2 Department of Neurology,First Hospital Affiliated to Shanxi Medical University,Taiyuan 030001,China

Objective This study was to identify Proteolipid protein 1(PLPl) mutations in 33 unrelated Chinese patients(P1-33) with Pelizaeus-Merzbacher disease(PMD) and prenatal diagnosis of 5 fetuses in 3 Chinese families with PMD *** Genomic DNA was extracted from peripheral bloods *** 19 or 20 weeks gestation,amniotic fluid sampling(AFS) was *** dosage was determined by Multiplex Ligationdependent Probe Amplification(MLPA).All 7 exons and exon-intron boundaries of PLPl gene were amplified and analyzed by direct DNA *** Of these 33 patients,there were 19 transitional,11 classical,and 3 congenital PMD according to the clinical and radiological *** duplications were identified in patients 1-23 with PMD,account for 69.7%(23/33).Their mothers were PLPl duplications carriers except P23'mother was *** hemizygous missense mutations including c.517C>T(p.P173S),c.709T>G(p.F237V),c.623G>T(p. G208V),c.567C>T(p.T156I),c.353C>T(p.T117R) and c.646C>T(p.P214S) were found in Patients 24-29 with PMD (18.2%),and their mothers were showed to be a heterozygote of those *** the results of prenatal diagnosis, in the family 1,For the prenatal diagnosis family 1,the 5 fetuses showed normal PLPl dosage and chromosome analysis demonstrated 3 46,XX and 2 46,XY chromosome patterns,*** fetus in family 2 revealed 3 cope of PLP1 which suggested a PLP1 duplication carrier after chromosome pattern was a 46,*** family 3,duplication of PLP1 was detected in the fetus imply as a PMD patient with 46,XY chromosome *** We identified 23 genomic duplications and 6 missense mutation of PLPl gene in 29 Chinese patients with PMD,account for 87.9%(29/33).Prenatal diagnoses for 5 fetuses in 3 PMD families were performed,which is useful and helpful for those *** is the first report about PLPl mutations and prenatal diagnosis in PMD patients in mainland of China.

关键词： Pelizaeus-Merzbacher disease PMD MLPA mutation

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Effects of puerarin on burn injury pain mediated by P2X3 receptor

Effects of puerarin on burn injury pain mediated by P2X3 rec...

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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： Chang-Shui XU,Jia-Ri LIN,Shuang-Mei LIU,Shang-Dong LIANG~* Department of Physiology,School of Basic Medical Sciences of Nanchang University,Nanchang 330006,China

Objective Peripheral administration of P2X agonists rapidly causes nocifensive behavior in experimental animals and pain sensation in *** of the nociceptive response to peripheral ATP is mediated by P2X *** shows that Puerarin may have anti-nociceptive response and the role of *** effects of Puerarin on rat burn injury pain mediated by P2X receptor was investigated at the present *** Superficial second degree foot/back burn injury models were ***-Dawley rat were randomly divided into sham paw burn group（SPB）,puerarin-treated paw unburned control group（PPC）,untreated superficial second degree paw burn group（UPB）,puerarin-treated superficial second degree paw burn group（PPB）,blank paw control group（BPC group）,sham back burn group（SBB）,puerarin-treated back unburned control group（PBC）,untreated superficial second degree back burn group（UBB）,puerarin-treated superficial second degree back burn group（PBB） and blank back control group（BBC）.Mechanical withdrawal threshold（MWT）and thermal withdrawal latency （TWL）were measured and the expressions of P2X receptor in dorsal root ganglion from test rats were detected by immunohisto-chemistry,RT-PCR,Western blot and in situ *** MWT and TWL in group UPB and PPB were lower than those in group SPB,PPC and BPC（P<0.01）after burn,and the MWT and TWL in group PPB were increased compared with those in group UPB after burn 48 h and 1 h respectively（P<0.05）.After 96 h,there was no difference in MWT and TWL between group PPB and group SPB（P>0.05）,and there also was no difference in MWT and TWL between PPC and BPC（P>0.05）.The MWT and TWL in group UPB were still decreased,there was difference between group UPB and group SPB（P<0.01）,and there also was difference between PPC and BPC （P<0.01）.At day 3 post burn,the expressions of P2X protein and mRNA in dorsal root ganglion from burn injury model rat in group UPB were increased significantly compared with those in other gro

关键词： P2X3 receptor puerarin burn pain

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Identification and functional studies of MLCl mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts(MLC)

Identification and functional studies of MLCl mutations in 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： Ajit Sigh DHAUCHAK David COLMAN Montreal Neurological Institute MontrealQuebecCanada

Objective Megalencephalic leukoencephalopathy with subcortical cysts(MLC,MIM# 604004) is an autosomal recessively inherited disease resulting from a deficiency of MLC1 *** study was to identify MLC1 mutations and perform their functional studies in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts(MLC).Methods The analysis of clinical features and MLC1 mutation screening were performed in 13 Chinese *** functional study of MLC1 variants was carried out by western blot,real-time PCR and confocal microscope.U373MG cells transfected by ***3.1-HA-MLCl wildtype and mutants were immunoassayed with antibodies of HA and calnexin,an ER *** A total of 10 MLC1 mutations were identified in these patients,including five novel missense mutations(c.65G>A,p.R22Q;c.95C>T,p.A32V;c.218G>A, p.G73E;c.823G>A,p.A275T;c.832T>C,p.Y278H),one novel splicing mutation(c.772-lG>C in IVS9-1),one novel small deletion(c.90730del,p.V30331 Odel),one known nonsense mutation(c.593delCTCA,p.Y198X) and two known missense mutations(c.206C>T,p.S69L;c.353C>T,p.T118M).Compared with the protein expression in WT,the protein expression in mutants A32V,G73E,S69L,T118M,Y198X,A275T and C278R were reduced in different level(all P<0.05),but no statistic differences was found for protein expression in mutant *** with mRNA expression in WT,that in mutants G73E,T118M,Y198X and A275T were at a lower level(P<0.05). WT MLC1 was at arstrocyte borders,whereas MLCl mutants R22Q and A32V are mainly intracellularly localized, and S69L,G73E,T118M are mildly retained at ***,other mutations are mainly at cell *** Ten DNA variations of MLCl gene were identified including seven novel *** mutants associated with MLC likely disrupt MLC1 protein and mRNA expression and *** would be the first report about MLC1 mutations in patients with megalencephalic leukoencephalopathy with subcortical cysts in China.

关键词： megalencephalic leukoencephalopathy with subcortical cysts MLCl mutation location expression

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