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Long-term Effects of Penicillin-induced Developmental Kindling on Cognitive Deficit and Related Gene Expressions in Hippocampus
Ni Hong1; Jiang Yu-Wu2; Ding Mei-Li1; Wang Zhe-Dong1; Tao Lu-Yang1; Wu Xi-Ru2
关键词Penicillin-induced Kindling Epilepsy Cognitive Deficit Molecular Mechanisms Camk Ii Alpha Znt Cck Prg-3
刊名PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
2009-04-01
DOI10.3724/SP.J.1206.2008.00576
36期:4页:480-490
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
资助者National Natural Science Foundation of China ; Natural Science Foundation of Jiangsu Province of China ; Natural Science Foundation of the Jiangsu Higher Education Institute of China ; National Natural Science Foundation of China ; Natural Science Foundation of Jiangsu Province of China ; Natural Science Foundation of the Jiangsu Higher Education Institute of China
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]INDUCED EPILEPTIFORM ACTIVITY ; NEONATAL SEIZURES ; WISTAR RAT ; PLASTICITY ; SINGLE ; MEMORY ; ACID
英文摘要

Epilepsy in children is associated with a broad spectrum of cognitive deficits, which is associated with hippocampal mossy fiber sprouting. The underlying molecular mechanisms involved in mossy fiber sprouting in hippocampus following developmental seizures are not completely known. The timing of cognitive dysfunction and the relation of this cognitive impairment to calcium/calmodulin-dependent protein kinase II (CaMK-II), plasticity related gene 3 (PRG-3), cholecystokinin (CCK), zinc transporter I and 3 (ZnT-1 and ZnT-3) in hippocampus were studied. A seizure was induced by penicillin quaque die alterna in Sprague-Dawley rats from postnatal day 29 (P29). Rats were assigned into the recurrent seizure group (RS, seizures were induced in eleven consecutive days, n=39) and the control group (NS, n=21). At 1.5 h, 3 h, 6 h and 12 h after the last seizure, apoptosis and autophagy were detected by transmission electronmicro-scopy (TEM) or in situ end labeling (TUNNEL). Electro-corticogram was observed after the last seizure. During P51 to P56, P81 to P84 and P92 to P95, the rats were tested for spatial learning and memory abilities with automatic Morris water maze task. On P95, mossy fiber sprouting and gene expressions in hippocampus were determined subsequently by Timm staining and real time RT-PCR methods. The results are as follows: a. TEM revealed the formation of autophagosomes and apoptosis in hippocampus after kindling. In the hippocampal neurons of the controls, chromatin and cytoplasmic organoids showed eumorphism with nuclear membrane integrity; 1.5 h after the last penicilin-induced recurrent seizures, "C" -morphous double membrane structure of dilated endocytoplasmic reticulum could be observed; 3 h after the last seizures, autophagosome appeared with manifest dilated endocytoplasmic reticulum; 6 similar to 12 h after the last seizures, the hippocampal neurons showed apoptotic feature such as nuclear chromatinic pyknosis and verge-aggregation. TUNNEL staining also showed elevated number of apoptosis neurons in hippocampus of RS group(P < 0.05). b. Vertex sharp transient wave and sharp wave were soon detected just in a few minutes afer the last seizure in RS group by Electrocorticogram. c. Escape latency. The escape latencies from the water maze were significantly longer in rats of RS group than that of the control at d5 of the first test, at d1 of the second test, and at d2 of the third test. d. Strategy analysis. RIDIT analysis showed that the scores were much worse in rats of RS group than that of the control at d4 and d5 of the first test. Moreover, the scores were much worse in rats of RS group than that of the control at the whole three days of both the second and third maze tests. e. Memory test. As for the value of distance in origin platform quadrant to total distance, the RS group seemed worse than the NS group in three maze tests(P < 0.05). f. Aberrant mossy fiber sprouting was seen in the inner molecular layer of the granule cells and the stratum pyramidale of CA3 subfield in RS group. g. Real time RT-PCR analysis showed decreased expression of CaMK II alpha and ZnT-1 in hippocampus of RS group than that in control group. Moreover, the four genes (CaMK II alpha, PRG-3, CCK and ZnT-3) in NS group and the two genes (CaMK II alpha and ZnT-1) in RS group showed copolymerization characteristic by cluster analysis. In addition, correlation and regression analysis demonstrated positive linear correlation among CaMK II alpha, CCK, PRG-3 and ZnT-3 in NS group and between CaMK II alpha and ZnT-1 in RS group.

It was concludd that recurrent developmental kindling induced by penicillin could cause not only autophagy and apoptosis in the earlier stage of brain damage, but also have long-term effects on cognitive function and hippocampal mossy fiber sprouting which may be associated with the down-regulated expression of CaMK II alpha and ZnT-1 in hippocampus.

语种中文
所属项目编号30470555 ; 30571909 ; 30870808 ; 30872666 ; BK2007509 ; 07KJB320103
资助者National Natural Science Foundation of China ; Natural Science Foundation of Jiangsu Province of China ; Natural Science Foundation of the Jiangsu Higher Education Institute of China ; National Natural Science Foundation of China ; Natural Science Foundation of Jiangsu Province of China ; Natural Science Foundation of the Jiangsu Higher Education Institute of China
WOS记录号WOS:000265411600013
引用统计
被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57410
专题北京大学第一临床医学院_儿科
作者单位1.Soochow Univ, Affiliated Childrens Hosp, Neurol Lab, Lab Aging & Nervous Dis, Suzhou 215003, Peoples R China
2.Peking Univ, Dept Pediat, Affiliated Hosp 1, Beijing 100034, Peoples R China
推荐引用方式
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Ni Hong,Jiang Yu-Wu,Ding Mei-Li,et al. Long-term Effects of Penicillin-induced Developmental Kindling on Cognitive Deficit and Related Gene Expressions in Hippocampus[J]. PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS,2009,36(4):480-490.
APA Ni Hong,Jiang Yu-Wu,Ding Mei-Li,Wang Zhe-Dong,Tao Lu-Yang,&Wu Xi-Ru.(2009).Long-term Effects of Penicillin-induced Developmental Kindling on Cognitive Deficit and Related Gene Expressions in Hippocampus.PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS,36(4),480-490.
MLA Ni Hong,et al."Long-term Effects of Penicillin-induced Developmental Kindling on Cognitive Deficit and Related Gene Expressions in Hippocampus".PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS 36.4(2009):480-490.
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