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在对僵住症易感性存在基因差异的小鼠中,于莫里斯水迷宫中的空间学习:脑源性神经营养因子脑室内给药的影响

Spatial learning in the Morris water maze in mice genetically different in the predisposition to catalepsy: the effect of intraventricular treatment with brain-derived neurotrophic factor.

作者信息

Kulikov Alexander V, Fursenko Daria V, Khotskin Nikita V, Bazovkina Daria V, Kulikov Victor A, Naumenko Vladimir S, Bazhenova Ekaterina Yu, Popova Nina K

机构信息

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russian Federation; Novosibirsk State University, Novosibirsk 630090, Russian Federation.

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russian Federation.

出版信息

Pharmacol Biochem Behav. 2014 Jul;122:266-72. doi: 10.1016/j.pbb.2014.04.009. Epub 2014 Apr 26.

Abstract

Hereditary catalepsy in mice is accompanied with volume reduction of some brain structures and high vulnerability to inflammatory agents. Here an association between hereditary catalepsy and spatial learning deficit in the Morris water maze (MWM) in adult mouse males of catalepsy-resistant AKR, catalepsy-prone CBA and AKR.CBA-D13Mit76 (D13) strains was studied. Recombinant D13 strain was created by means of the transfer of the CBA-derived allele of the major gene of catalepsy to the AKR genome. D13 mice showed a low MWM performance in the acquisition test and high expression of the gene coding proinflammatory interleukin-6 (Il-6) in the hippocampus and cortex compared with mice of the parental AKR and CBA strains. An acute ivc administration of 300 ng of brain derived neurotrophic factor (BDNF) normalized the performance in the MWM, but did not decrease the high Il-6 gene expression in the brain of D13 mice. These results indicated a possible association between the hereditary catalepsy, MWM performance, BDNF and level of Il-6 mRNA in the brain, although the relation between these characteristics seems to be more complex. D13 recombinant mice with deficit of spatial learning is a promising model for study of the genetic and molecular mechanisms of learning disorders as well as for screening potential cognitive enhancers.

摘要

小鼠遗传性僵住症伴有某些脑结构体积减小以及对炎症因子高度敏感。在此,研究了抗僵住症的AKR、易患僵住症的CBA以及AKR.CBA-D13Mit76(D13)品系成年雄性小鼠遗传性僵住症与莫里斯水迷宫(MWM)空间学习缺陷之间的关联。重组D13品系是通过将CBA来源的僵住症主要基因等位基因转移到AKR基因组而创建的。与亲本AKR和CBA品系的小鼠相比,D13小鼠在习得性测试中MWM表现较差,且海马体和皮质中编码促炎白细胞介素-6(Il-6)的基因表达较高。静脉注射300 ng脑源性神经营养因子(BDNF)可使D13小鼠在MWM中的表现恢复正常,但并未降低其脑中Il-6基因的高表达。这些结果表明遗传性僵住症、MWM表现、BDNF与脑中Il-6 mRNA水平之间可能存在关联,尽管这些特征之间的关系似乎更为复杂。空间学习存在缺陷的D13重组小鼠是研究学习障碍的遗传和分子机制以及筛选潜在认知增强剂的一个有前景的模型。

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